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Hiding in plain sight: an evolutionary approach to the South American Zika outbreak and its future consequences

ABSTRACT

Emerging Infectious Diseases (EID) pose a world-wide health and socio-economic threat. Accelerating climate change and globalization are exposing unforeseen ways that pathogens cope with their surroundings. The 2015 Zika virus (ZIKV) outbreak was an example of expansion into previously inaccessible fitness spaces, causing a sudden epidemic. Recent studies indicating the subsequent decrease in symptomatic cases means the virus is in remission, currently poses little threat, and therefore can be ignored. We present an evolutionary scenario derived from the Stockholm Paradigm, of oscillating phases of expansion and isolation, accompanied by changes in transmission, persistence, virulence, and pathology. Chief among these is the likelihood that asymptomatic strains are constantly transmitted sexually. This suggests that the currently quiescent virus retains capacities to reemerge abruptly and spread rapidly in an arena of changing opportunity.

KEY WORDS:
Emerging Infectious Disease; outbreaks; Stockholm Paradigm; Zika virus

Background

Emerging Infectious Diseases (EID) constitute a global threat to humans and the animals and plants upon which they depend socio-economically. And while there appears to be a general evolutionary dynamic relating emerging diseases with climate change (Brooks and Boeger 2019Brooks DR, Boeger WA (2019) Climate change and emerging infectious diseases: Evolutionary complexity in action. Current Opinion in Systems Biology 13: 75-81. https://doi.org/10.1016/j.coisb.2018.11.001
https://doi.org/10.1016/j.coisb.2018.11....
, Brooks et al. 2019Brooks DR, Hoberg EP, Boeger WA (2019) The Stockholm Paradigm: Climate Change and Emerging Disease. University of Chicago Press, Chicago., Hoberg and Brooks 2015Hoberg EP, Brooks DR (2015) Evolution in action: climate change, biodiversity dynamics and emerging infectious disease. Philosophical Transactions of the Royal Society B-Biological Sciences 370: 7. https://doi.org/10.1098/rstb.2013.0553
https://doi.org/10.1098/rstb.2013.0553...
), each new emergence event reveals novel dimensions about pathogen capabilities. One of the most notable is a new variant of the Asian strain of Zika virus (ZIKV), source of the highly publicized New World outbreaks of 2015.

The rapidity with which Zika emerged in Latin America, coupled with a high proportion of neurological deficits in babies born to Zika-positive mothers warranted special attention. How did it come to be in the New World and why did it behave differently there? These issues were discussed peripherally, but initial reaction was muted. Reports identified seasonal changes in mosquito dynamics or herd immunity as the underlying cause of the pandemic (Silva et al. 2017Silva JVJ, Lopes TRR, de Oliveira EF, Oliveira RAD, Gil L (2017) Perspectives on the Zika outbreak: herd immunity, antibodydependent enhancement and vaccine. Revista do Instituto de Medicina Tropical de São Paulo 59: 2. https://doi.org/10.1590/s1678-9946201759021
https://doi.org/10.1590/s1678-9946201759...
). Vaccine-development and vector-control plans were hastily initiated, but before any of them bore fruit, the disease seemingly disappeared, undermining calls for further action (Cohen 2018Cohen J (2018) Infectious disease steep drop in Zika cases undermines vaccine trial. Science 361: 1055-1056. https://doi.org/10.1126/science.361.6407.1055
https://doi.org/10.1126/science.361.6407...
). It is highly unlikely that a virus with a half century history of epidemics can simply vanish after the most recent and severe outbreak. Additionally, the Asian strain, against which complete immunity was reported in monkeys (Dudley et al. 2016Dudley DM, Aliota MT, Mohr EL, Weiler AM, Lehrer-Brey G, Weisgrau KL, Mohns MS, Breitbach ME, Rasheed MN, Newman CM, Gellerup DD, Moncla LH, Post J, Schultz-Darken N, Schotzko ML, Hayes JM, Eudailey JA, Moody MA, Permar SR, O’Connor SL, Rakasz EG, Simmons HA, Capuano S, Golos TG, Osorio JE, Friedrich TC, O’Connor DH (2016) A rhesus macaque model of Asian-lineage Zika virus infection. Nature Communications 7: 9. https://doi.org/10.1038/ncomms12204
https://doi.org/10.1038/ncomms12204...
) has already caused three additional outbreaks in Asia and South-America. In this opinion piece, we draw attention to aspects of the evolutionary biology of Zika that may help explain how a previously insignificant disease became a major threat to infant neural development, why it could recur, and why it could become a global problem.

Transmission

Most studies describe Zika as a ‘mosquito-borne arbovirus’ (Dick 1952Dick GWA (1952) Zika virus (II). Pathogenicity and physical properties. Transactions of the Royal Society of Tropical Medicine and Hygiene 46: 521-534. https://doi.org/10.1016/0035-9203(52)90043-6
https://doi.org/10.1016/0035-9203(52)900...
, Duffy et al. 2009Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, Pretrick M, Marfel M, Holzbauer S, Dubray C, Guillaumot L, Griggs A, Bel M, Lambert AJ, Laven J, Kosoy O, Panella A, Biggerstaff BJ, Fischer M, Hayes EB (2009) Zika Virus Outbreak on Yap Island, Federated States of Micronesia. New England Journal of Medicine 360: 2536-2543. https://doi.org/10.1056/NEJMoa0805715
https://doi.org/10.1056/NEJMoa0805715...
, Mladinich et al. 2017Mladinich MC, Schwedes J, Mackow ER (2017) Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells. Mbio 8: 17. https://doi.org/10.1128/mBio.00952-17
https://doi.org/10.1128/mBio.00952-17...
, Smith et al. 2018Smith DR, Sprague TR, Hollidge BS, Valdez SM, Padilla SL, Bellanca SA, Golden JW, Coyne SR, Kulesh DA, Miller LJ, Haddow AD, Koehler JW, Gromowski GD, Jarman RG, Alera MTP, Yoon IK, Buathong R, Lowen RG, Kane CD, Minogue TD, Bavari S, Tesh RB, Weaver SC, Linthicum KJ, Pitt ML, Nasar F (2018) African and Asian Zika Virus Isolates Display Phenotypic Differences Both In Vitro and In Vivo. American Journal of Tropical Medicine and Hygiene 98: 432-444. https://doi.org/10.4269/ajtmh.17-0685
https://doi.org/10.4269/ajtmh.17-0685...
). The virus was first collected from rhesus monkeys, and subsequent studies showed that the mosquitoes Aedes africanus (Theobald, 1901) and Aedes aegypti (Linnaeus, 1762) were competent vectors of the pathogen (Dick 1952Dick GWA (1952) Zika virus (II). Pathogenicity and physical properties. Transactions of the Royal Society of Tropical Medicine and Hygiene 46: 521-534. https://doi.org/10.1016/0035-9203(52)90043-6
https://doi.org/10.1016/0035-9203(52)900...
).

Within twenty years of its discovery, a variant of Zika was found in southern Asia, and was detected in local mosquito populations. The Asian strain was little studied until a 2007 outbreak on the island of Yap was suspected of infecting thousands of people (Duffy et al. 2009Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, Pretrick M, Marfel M, Holzbauer S, Dubray C, Guillaumot L, Griggs A, Bel M, Lambert AJ, Laven J, Kosoy O, Panella A, Biggerstaff BJ, Fischer M, Hayes EB (2009) Zika Virus Outbreak on Yap Island, Federated States of Micronesia. New England Journal of Medicine 360: 2536-2543. https://doi.org/10.1056/NEJMoa0805715
https://doi.org/10.1056/NEJMoa0805715...
). In 2015, the largest outbreak yet resulted in thousands of cases of microcephaly in Brazil and emergences of Guillain-Barré syndrome in the South-Pacific and in Colombia (Mendez et al. 2017Mendez N, Oviedo-Pastrana M, Mattar S, Caicedo-Castro I, Arrieta G (2017) Zika virus disease, microcephaly and Guillain-Barre syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015-2017. Archives of Public Health 75: 11. https://doi.org/10.1186/s13690-017-0233-5
https://doi.org/10.1186/s13690-017-0233-...
). As expected, medical and epidemiological research scrambled to get a hold of the new virus, and studies initially focused on controlling the suspected vector A. aegypti. It is not completely without base to assume that the mosquito transfers Zika, since closely related viruses (chikungunya and dengue) have stable populations in South-America and are transmitted by A. aegypti. Nevertheless, although this mosquito is still a competent vector of the African strain, it transmits the American and Asian Zika strains much less efficiently (Roundy et al. 2017Roundy CM, Azar SR, Rossi SL, Huang JH, Leal G, Yun R, Fernandez-Salas I, Vitek CJ, Paploski IAD, Kitron U, Ribeiro GS, Hanley KA, Weaver SC, Vasilakis N (2017) Variation in Aedes aegypti Mosquito Competence for Zika Virus Transmission. Emerging Infectious Diseases 23: 625-632. https://doi.org/10.3201/eid2304.161484
https://doi.org/10.3201/eid2304.161484...
). Additionally, none of the widespread, related mosquito species seem capable of transmitting the virus (Dodson et al. 2018Dodson BL, Pujhari S, Rasgon JL (2018) Vector competence of selected North American Anopheles and Culex mosquitoes for Zika virus. Peerj 6: 10. https://doi.org/10.7717/peerj.4324
https://doi.org/10.7717/peerj.4324...
). Furthermore, the peak of Zika related cases appears to have been sustained outside of the mosquito-breeding season, which suggests the existence of an alternate transmission route underlying a vector-borne pathway (Ferdousi et al. 2019Ferdousi T, Cohnstaedt LW, McVey DS, Scoglio CM (2019) Understanding the survival of Zika virus in a vector interconnected sexual contact network. Scientific Reports 9: 7253. https://doi.org/10.1038/s41598-019-43651-3
https://doi.org/10.1038/s41598-019-43651...
).

We must revisit previous cases and explore a neglected aspect of Zika biology. Along with the sudden change in virulence, the 2007 Zika outbreak in Yap produced one of the first documented cases of the sexual transmission of the virus (Foy et al. 2011Foy BD, Kobylinski KC, Foy JLC, Blitvich BJ, da Rosa AT, Haddow AD, Lanciotti RS, Tesh RB (2011) Probable Non-Vector-borne Transmission of Zika Virus, Colorado, USA. Emerging Infectious Diseases 17: 880-882. https://doi.org/10.3201/eid1705.101939
https://doi.org/10.3201/eid1705.101939...
, Sakkas et al. 2018Sakkas H, Bozidis P, Giannakopoulos X, Sofikitis N, Papadopoulou C (2018) An Update on Sexual Transmission of Zika Virus. Pathogens 7: 14. https://doi.org/10.3390/pathogens7030066
https://doi.org/10.3390/pathogens7030066...
). Little studied at the time, the number of documented cases of sexually acquired Zika has increased (Moreira et al. 2017Moreira J, Peixoto TM, Siqueira AM, Lamas CC (2017) Sexually acquired Zika virus: a systematic review. Clinical Microbiology and Infection 23: 296-305. https://doi.org/10.1016/j.cmi.2016.12.027
https://doi.org/10.1016/j.cmi.2016.12.02...
). Furthermore, human male patients shed Zika RNA in the semen six months after the remission of their clinical symptoms (Barzon et al. 2016Barzon L, Pacenti M, Franchin E, Lavezzo E, Trevisan M, Sgarabotto D, Palu G (2016) Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016. Eurosurveillance 21: 2-5. https://doi.org/10.2807/1560-7917.es.2016.21.32.30316
https://doi.org/10.2807/1560-7917.es.201...
), and the virus increases the rate of spermiogenesis (Sakkas et al. 2018Sakkas H, Bozidis P, Giannakopoulos X, Sofikitis N, Papadopoulou C (2018) An Update on Sexual Transmission of Zika Virus. Pathogens 7: 14. https://doi.org/10.3390/pathogens7030066
https://doi.org/10.3390/pathogens7030066...
). With as many as 80% of infected adults reporting no symptoms, sexual contact could be an effective mode of transmission (Freour et al. 2016Freour T, Mirallie S, Hubert B, Splingart C, Barriere P, Maquart M, Leparc-Goffart I (2016) Sexual transmission of Zika virus in an entirely asymptomatic couple returning from a Zika epidemic area, France, April 2016. Eurosurveillance 21: 10-12. https://doi.org/10.2807/1560-7917.es.2016.21.23.30254
https://doi.org/10.2807/1560-7917.es.201...
).

Phylogenetic studies show that Zika originated in Africa and dispersed to Asia, likely as a result of human migrations approximately 60 years ago (Smith et al. 2018Smith DR, Sprague TR, Hollidge BS, Valdez SM, Padilla SL, Bellanca SA, Golden JW, Coyne SR, Kulesh DA, Miller LJ, Haddow AD, Koehler JW, Gromowski GD, Jarman RG, Alera MTP, Yoon IK, Buathong R, Lowen RG, Kane CD, Minogue TD, Bavari S, Tesh RB, Weaver SC, Linthicum KJ, Pitt ML, Nasar F (2018) African and Asian Zika Virus Isolates Display Phenotypic Differences Both In Vitro and In Vivo. American Journal of Tropical Medicine and Hygiene 98: 432-444. https://doi.org/10.4269/ajtmh.17-0685
https://doi.org/10.4269/ajtmh.17-0685...
). There is evidence that a sexually transmitted strain or genotype of Zika was present in the African lineage (Sakkas et al. 2018Sakkas H, Bozidis P, Giannakopoulos X, Sofikitis N, Papadopoulou C (2018) An Update on Sexual Transmission of Zika Virus. Pathogens 7: 14. https://doi.org/10.3390/pathogens7030066
https://doi.org/10.3390/pathogens7030066...
), along with the common vector-borne strain. When expanding its distribution to Asia, Zika faced new mosquito taxa, but the human host remained constant. The sexually-transmitted variant (Sakkas et al. 2018Sakkas H, Bozidis P, Giannakopoulos X, Sofikitis N, Papadopoulou C (2018) An Update on Sexual Transmission of Zika Virus. Pathogens 7: 14. https://doi.org/10.3390/pathogens7030066
https://doi.org/10.3390/pathogens7030066...
) had the advantage of not having to expand to new vectors and its prevalence seems to have been amplified by selection as a result. The Asian strain introduced to the New World thus already had an enhanced capacity for sexual transmission relative to the African strain. Zika must be seen as a virus that persists through an interconnected network of both vectored and sexual transmission, increasing and expanding the risk factors associated with potential pandemics (Ferdousi et al. 2019Ferdousi T, Cohnstaedt LW, McVey DS, Scoglio CM (2019) Understanding the survival of Zika virus in a vector interconnected sexual contact network. Scientific Reports 9: 7253. https://doi.org/10.1038/s41598-019-43651-3
https://doi.org/10.1038/s41598-019-43651...
).

Pathogenicity and virulence

Pathogen-host associations do not always produce disease, even when the pathogen multiplies extensively in the host. As well, though in many pathogens (e.g. Influenza A and B virus) a high pathogen replication rate is associated with elevated pathogenicity (the potential of the pathogen to cause disease in a single host specimen), virulence (the measure of how much damage a pathogen causes to the host) is not necessarily associated with high rates of infection (e.g. Hepatitis C virus), whereas an asymptomatic disease may spread through a high number of propagules (e.g. Herpes simplex virus) (Anderson and May 1982Anderson RM, May RM (1982) Coevolution of hosts and parasites. Parasitology 85: 411-426. https://doi.org/10.1017/s0031182000055360
https://doi.org/10.1017/s003118200005536...
, May and Anderson 1983May RM, Anderson RM (1983) Epidemiology and genetics in the coevolution of parasites and hosts. Proceedings of the Royal Society Series B-Biological Sciences 219: 281-313. https://doi.org/10.1098/rspb.1983.0075
https://doi.org/10.1098/rspb.1983.0075...
).

Experiments using mouse models show that diverse Zika lineages exhibit striking differences in both pathogenicity and virulence. African strains were 10,000-fold more virulent, and produced uniformly fatal disease in mouse models, as opposed to the significantly lower mortality rate of the Asian strain (Smith et al. 2018Smith DR, Sprague TR, Hollidge BS, Valdez SM, Padilla SL, Bellanca SA, Golden JW, Coyne SR, Kulesh DA, Miller LJ, Haddow AD, Koehler JW, Gromowski GD, Jarman RG, Alera MTP, Yoon IK, Buathong R, Lowen RG, Kane CD, Minogue TD, Bavari S, Tesh RB, Weaver SC, Linthicum KJ, Pitt ML, Nasar F (2018) African and Asian Zika Virus Isolates Display Phenotypic Differences Both In Vitro and In Vivo. American Journal of Tropical Medicine and Hygiene 98: 432-444. https://doi.org/10.4269/ajtmh.17-0685
https://doi.org/10.4269/ajtmh.17-0685...
). When comparing various Asian strains with the one related directly to that responsible for the American outbreak, the Asian strain showed 10 to 100-fold higher titer numbers and a nine times higher mortality than the American (Beaver et al. 2018Beaver JT, Lelutiu N, Habib R, Skountzou I (2018) Evolution of Two Major Zika Virus Lineages: Implications for Pathology, Immune Response, and Vaccine Development. Frontiers in Immunology 9: 17. https://doi.org/10.3389/fimmu.2018.01640
https://doi.org/10.3389/fimmu.2018.01640...
). If vector-borne transmission was overshadowed by sexual transmission in the evolution of Zika in Asia, efficient infection would rely increasingly on host condition (Ewald 2004Ewald PW (2004) Evolution of virulence. Infectious Disease Clinics of North America 18: 1-15. https://doi.org/10.1016/S0891-5520(03)00099-0
https://doi.org/10.1016/S0891-5520(03)00...
) explaining the apparent decrease in both virulence and pathogenicity. Studies of these two measures on human populations revealed that asymptomatic infections were substantially lower during African outbreaks than during Asian ones (Simonin et al. 2017Simonin Y, van Riel D, de Perre PV, Rockx B, Salinas S (2017) Differential virulence between Asian and African lineages of Zika virus. Plos Neglected Tropical Diseases 11: 8. https://doi.org/10.1371/journal.pntd.0005821
https://doi.org/10.1371/journal.pntd.000...
); 80% of the Yap Island cases are thought to have been asymptomatic (Duffy et al. 2009Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, Pretrick M, Marfel M, Holzbauer S, Dubray C, Guillaumot L, Griggs A, Bel M, Lambert AJ, Laven J, Kosoy O, Panella A, Biggerstaff BJ, Fischer M, Hayes EB (2009) Zika Virus Outbreak on Yap Island, Federated States of Micronesia. New England Journal of Medicine 360: 2536-2543. https://doi.org/10.1056/NEJMoa0805715
https://doi.org/10.1056/NEJMoa0805715...
).

These data suggest that the Asian strain of Zika introduced to the New World had made the evolutionary transition from primarily vector-transmitted to primarily sexually-transmitted. With the majority of the cases being asymptomatic, the extent to which the STD variant has spread through human populations is hard to estimate. Nevertheless, the distance the virus has traveled and the speed with which it conquered the Americas suggests a novel STD variant underlying the visible outbreaks. Additionally, given the high rate of asymptomatic cases, it is by now extremely difficult to tie the presence of ZIKV to registered outbreaks, since most carriers in between outbreaks and during the 2015 Brazilian outbreak most likely never produced symptoms. We must therefore assume that the distribution of the virus shows a significant mismatch with that of documented outbreaks. That contention is consistent with general observations of pathogen distribution, where the geographic range of the pathogen is always larger than the distribution of disease (Audy 1958Audy JR (1958) The localization of disease with special reference to the zoonoses. Transactions of the Royal Society of Tropical Medicine and Hygiene 52: 309-328. https://doi.org/10.1016/0035-9203(58)90045-2
https://doi.org/10.1016/0035-9203(58)900...
).

Pathology

The pathology of the South American strain set this epidemic apart from previous outbreaks. Microcephaly, Guillain-Barré syndrome and neural damage had never before been associated with the ZIKV, and were the main reasons the American Zika qualified as an EID (Petersen et al. 2016Petersen LR, Jamieson DJ, Powers AM, Honein MA (2016) Zika Virus. New England Journal of Medicine 374: 1552-1563. https://doi.org/10.1056/NEJMra1602113
https://doi.org/10.1056/NEJMra1602113...
). The question of ‘how did the virus acquire new pathological characteristics’ immediately surfaced. Genetic screening found a VNDT sequence motif in the virus strand capable of neuro-invasion (Annamalai et al. 2017Annamalai AS, Pattnaik A, Sahoo BR, Muthukrishnan E, Natarajan SK, Steffen D, Vu HLX, Delhon G, Osorio FA, Petro TM, Xiang SH, Pattnaik AK (2017) Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated and Defective in Neuroinvasion. Journal of Virology 91: 16. https://doi.org/10.1128/jvi.01348-17
https://doi.org/10.1128/jvi.01348-17...
), which was able to cross the blood-brain-barrier through infecting microvascular endothelial cells (Mladinich et al. 2017Mladinich MC, Schwedes J, Mackow ER (2017) Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells. Mbio 8: 17. https://doi.org/10.1128/mBio.00952-17
https://doi.org/10.1128/mBio.00952-17...
). Using the same patho-mechanism, this strain can also pass through the placenta, enter the brain of the embryo and cause serious neural damage (Ahmad et al. 2018Ahmad F, Siddiqui A, Kamal MA, Sohrab SS (2018) Inhibition of Neurogenesis by Zika Virus Infection. Cns & Neurological Disorders-Drug Targets 17: 78-86. https://doi.org/10.2174/1871527317666180202115114
https://doi.org/10.2174/1871527317666180...
, Mladinich et al. 2017Mladinich MC, Schwedes J, Mackow ER (2017) Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells. Mbio 8: 17. https://doi.org/10.1128/mBio.00952-17
https://doi.org/10.1128/mBio.00952-17...
). This VNDT motif is polymorphic in both African and Asian strands, but American ZIKV isolates carry only the one VNDT morph (Mladinich et al. 2017Mladinich MC, Schwedes J, Mackow ER (2017) Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells. Mbio 8: 17. https://doi.org/10.1128/mBio.00952-17
https://doi.org/10.1128/mBio.00952-17...
), suggesting a recent change in the genome of the virus. Additionally, the abrupt loss of genetic variation in the newly emergent American strand corresponds with the founder effect (Provine 2004Provine WB (2004) Ernst Mayr: genetics and speciation. Genetics 167: 1041-1046.), when a small subset of the original population establishes a lineage, with different characteristics due to the decreased genetic variation. When applied to Zika, the Brazilian lineage is derived from the VNDT morph capable of neuro-invasion and represents a subset of the original ZIKV populations. Furthermore, recent studies showed that ZIKV is capable of causing long-term fetal developmental anomalies, including autism spectrum disorder, and other than neural damage, and poses a threat to pregnant mothers, regardless of the declining epidemic (Chakhtoura et al. 2018Chakhtoura N, Hazra R, Spong CY (2018) Zika virus: a public health perspective. Current Opinion in Obstetrics & Gynecology 30: 116-122. https://doi.org/10.1097/gco.0000000000000440
https://doi.org/10.1097/gco.000000000000...
, Vianna et al. 2018Vianna P, Gomes JD, Boquett JA, Fraga LR, Schuch JB, Vianna FSL, Schuler-Faccini L (2018) Zika Virus as a Possible Risk Factor for Autism Spectrum Disorder: Neuroimmunological Aspects. Neuroimmunomodulation 25: 320-327. https://doi.org/10.1159/000495660
https://doi.org/10.1159/000495660...
, Walker et al. 2019Walker CL, Little MTE, Roby JA, Armistead B, Gale M, Rajagopal L, Nelson BR, Ehinger N, Mason B, Nayeri U, Curry CL, Waldorf KMA (2019) Zika virus and the nonmicrocephalic fetus: why we should still worry. American Journal of Obstetrics and Gynecology 220: 45-56. https://doi.org/10.1016/j.ajog.2018.08.035
https://doi.org/10.1016/j.ajog.2018.08.0...
).

A Specific Case of a General Principle

The Zika story highlights all the elements of the Stockholm Paradigm (Textbox 1). Beginning in Africa, where it is primarily a mosquito-transmitted pathogen, in keeping with the ancestral legacy of its closest relatives. African ZIKV also demonstrates plasticity in transmission, being capable of sexual transmission at a low level. When climate changes created hospitable connections out of Africa through the Arabian peninsula, ancestral ZIKV expanded geographically into Asia via ecological fitting. During this generalization in geographical fitness space, ZIKV was exposed to novel mosquitos but the same ancestral vertebrate hosts (including humans). That generalization in host fitness space led to decreased and diffuse selection focused on mosquito transmission with concomitant increased and focused selection on sexual transmission, produced an isolated, specialized form of ZIKV in Asia. The new specialized Asian form became what it is today, predominantly a sexually transmitted pathogen that retains some capacity for facultative transmission by mosquitos. As anticipated by the Stockholm Paradigm, the isolation of ZIKV in Asia allowed novel capacities to emerge - cases of sexual transmission are documented during the 2007 outbreak (Foy et al. 2011Foy BD, Kobylinski KC, Foy JLC, Blitvich BJ, da Rosa AT, Haddow AD, Lanciotti RS, Tesh RB (2011) Probable Non-Vector-borne Transmission of Zika Virus, Colorado, USA. Emerging Infectious Diseases 17: 880-882. https://doi.org/10.3201/eid1705.101939
https://doi.org/10.3201/eid1705.101939...
) and transmission efficiency of the original arthropod vector decreased significantly (Roundy et al. 2017Roundy CM, Azar SR, Rossi SL, Huang JH, Leal G, Yun R, Fernandez-Salas I, Vitek CJ, Paploski IAD, Kitron U, Ribeiro GS, Hanley KA, Weaver SC, Vasilakis N (2017) Variation in Aedes aegypti Mosquito Competence for Zika Virus Transmission. Emerging Infectious Diseases 23: 625-632. https://doi.org/10.3201/eid2304.161484
https://doi.org/10.3201/eid2304.161484...
). At this point, the evolutionary trajectory for ZIKV involved oscillation from an initial single specialized form, subsequently to a generalized form and most recently expansion of two current forms. Further geographic expansion into the Pacific was accomplished by human agencies, leading to long-distance colonization by small founder populations of the Asian ZIKV, characterized by genetic changes. Asian ZIKV initially became more generalized in geographical fitness space globally, but quickly began showing evidence of founder effect divergence. For example, a founder population of one of those strains was subsequently introduced to South America. There, novel capacities in microhabitat preferences, namely, the brain and developing fetuses allowed the emergent South American ZIKV to rapidly expand into novel microhabitat fitness space. High human population densities in urban centers, coupled with transportation of people and goods led to a rapid dispersion (generalization) of the new form in geographical fitness space. Somewhat more slowly, but inexorably, novel vertebrate hosts were colonized and the virus spread geographically. It is likely that mosquito-borne transmission plays a crucial role in expanding the host range of the virus.

Textbox 1. The Stockholm Paradigm.

For more than 60 years, pathogens and hosts have been envisioned as engaged in evolutionary arms races, each participant mutually modifying the other. The increasing specialization of a pathogen with respect to a given host should be accompanied by decreasing ability to survive in association with other hosts. In order to switch to a new host, therefore, a pathogen must first evolve novel host-use capacities and then colonize a suitable new host. Given the absence of a mechanism by which such mutations could emerge in response to the presence of any particular novel host, coevolution has been viewed as a kind of firewall against emerging disease; host switches should not be common (Thompson 1994Thompson JN (1994) The coevolutionary process. University of Chicago, Chicago., Wolfe et al. 2007Wolfe ND, Dunavan CP, Diamond J (2007) Origins of major human infectious diseases. Nature 447: 279-283. https://doi.org/10.1038/nature05775
https://doi.org/10.1038/nature05775...
). And yet, host switching happens often in real time and phylogenetic studies indicate that host switching has always been common (Brooks and Boeger 2019Brooks DR, Hoberg EP, Boeger WA (2019) The Stockholm Paradigm: Climate Change and Emerging Disease. University of Chicago Press, Chicago., Hoberg and Brooks 2008Hoberg EP, Brooks DR (2008) A macroevolutionary mosaic: episodic host-switching, geographical colonization and diversification in complex host-parasite systems. Journal of Biogeography 35: 1533-1550. https://doi.org/10.1111/j.1365-2699.2008.01951.x
https://doi.org/10.1111/j.1365-2699.2008...
, 2015Hoberg EP, Brooks DR (2015) Evolution in action: climate change, biodiversity dynamics and emerging infectious disease. Philosophical Transactions of the Royal Society B-Biological Sciences 370: 7. https://doi.org/10.1098/rstb.2013.0553
https://doi.org/10.1098/rstb.2013.0553...
). This has been called the Parasite Paradox; how can ecologically specialized pathogens switch hosts easily?

The Stockholm Paradigm resolves the paradox by recognizing the influence of two fundamental but often overlooked aspects of Darwinian evolution. First, inherited traits of adaptive significance may be highly specialized but are also phylogenetically conservative (Brooks and McLennan 2002Brooks DR, McLennan DA (2002) The nature of diversity: an evolutionary voyage of discovery. University of Chigaco Press, Chicago, Illinois., Darwin 1872Darwin C (1872) The origin of species. Murray, London.). The conservative nature of pre-existing specialized adaptations, aided by phenotypic plasticity and co-option produces ecological fitting (Agosta et al. 2010Agosta SJ, Janz N, Brooks DR (2010) How specialists can be generalists: resolving the “parasite paradox” and implications for emerging infectious disease. Zoologia 27: 151-162. https://doi.org/10.1590/s1984-46702010000200001
https://doi.org/10.1590/s1984-4670201000...
, Brooks and McLennan 2002Brooks DR, McLennan DA (2002) The nature of diversity: an evolutionary voyage of discovery. University of Chigaco Press, Chicago, Illinois., Janzen 1985Janzen DH (1985) On ecological fitting. Oikos 45: 308-310. https://doi.org/10.2307/3565565
https://doi.org/10.2307/3565565...
), the ability of pathogens to take advantage of novel host opportunities based on pre-existing specializations. Entire pathogen communities ranging across a geographically expansive wide range of habitats, may be structured by ecological fitting (Brooks et al. 2006Brooks DR, Leon-Regagnon V, McLennan DA, Zelmer D (2006) Ecological fitting as a determinant of the community structure of platyhelminth parasites of anurans. Ecology 87: S76-S85. https://doi.org/10.1890/0012-9658(2006)87[76:efaado]2.0.co;2
https://doi.org/10.1890/0012-9658(2006)8...
), suggesting that the potential for changing hosts through ecological fitting is large (fitness space is “sloppy”: Agosta 2006Agosta SJ (2006) On ecological fitting, plant-insect associations, herbivore host shifts, and host plant selection. Oikos 114: 556-565. https://doi.org/10.1111/j.2006.0030-1299.15025.x
https://doi.org/10.1111/j.2006.0030-1299...
, Agosta and Klemens 2008Agosta SJ, Klemens JA (2008) Ecological fitting by phenotypically flexible genotypes: implications for species associations, community assembly and evolution. Ecology Letters 11: 1123-1134. https://doi.org/10.1111/j.1461-0248.2008.01237.x
https://doi.org/10.1111/j.1461-0248.2008...
). Second, strong coevolutionary arms race dynamics are intimate affairs, affecting a given pathogen and a given host at a given place. As a result, they have no impact on other potential pathogen-host associations in other places. The efficacy of a coevolutionary arms race is weakened in proportion to the number of different hosts occupied. Modelling efforts show that, as hosts are added, specialized coevolutionary arms race dynamics become generalized Red Queen dynamics in which the pathogen has all the advantages, because all hosts are focused on a single pathogen while the pathogen can take advantage of variation among multiple hosts (Araujo et al. 2015Araujo SBL, Braga MP, Brooks DR, Agosta SJ, Hoberg EP, von Hartenthal FW, Boeger WA (2015) Understanding Host-Switching by Ecological Fitting. Plos One 10: 17. https://doi.org/10.1371/journal.pone.0139225
https://doi.org/10.1371/journal.pone.013...
, Braga et al. 2018Braga MP, Araujo SBL, Agosta S, Brooks D, Hoberg E, Nylin S, Janz N, Boeger WA (2018) Host use dynamics in a heterogeneous fitness landscape generates oscillations in host range and diversification. Evolution 72: 1773-1783. https://doi.org/10.1111/evo.13557
https://doi.org/10.1111/evo.13557...
, Brooks et al. 2019Brooks DR, Hoberg EP, Boeger WA (2019) The Stockholm Paradigm: Climate Change and Emerging Disease. University of Chicago Press, Chicago.). Environmental perturbations change the opportunity space for pathogens, altering trophic structures and geographic distributions. They increase the chances that a pathogen will encounter susceptible, but previously unexposed, hosts. Highly specialized pathogens become more generalized by virtue of occupying a larger proportion of susceptible hosts. Environmental stability reduces connectivity in fitness space, producing localized isolated pathogen-host associations in which novel specialized variants may arise and survive. Though arising in a localized context, such novel variants often have substantial potential for ecological fitting whenever the next perturbation creates new opportunities. Over long periods of time, pathogen diversity is thus shaped by increases and decreases in host range (the Oscillation Hypothesis: Janz and Nylin 2008Janz N, Nylin S (2008) The Oscillation Hypothesis of Host-Plant Range and Speciation. In: Tilmon KJ (Ed) Specialization, Speciation, and Radiation: The Evolutionary Biology of Herbivorous Insects. Berkeley, University of California Press, 203-215., Janz et al. 2006Janz N, Nylin S, Wahlberg N (2006) Diversity begets diversity: host expansions and the diversification of plant-feeding insects. Bmc Evolutionary Biology 6: 10. https://doi.org/10.1186/1471-2148-6-4
https://doi.org/10.1186/1471-2148-6-4...
) and expansions and isolations in geographic distribution (the Taxon Pulse: Erwin 1981Erwin TL (1981) Taxon Pulses, Vicariance, and Dispersal: An Evolutionary Synthesis illustrated by Carabid Beetles. In: Gareth NaDER (Ed) Vicariance Biogeography: A Critique. Columbia University Press, New York, 159-196., Halas et al. 2005Halas D, Zamparo D, Brooks DR (2005) A historical biogeographical protocol for studying biotic diversification by taxon pulses. Journal of Biogeography 32: 249-260. https://doi.org/10.1111/j.1365-2699.2004.01147.x
https://doi.org/10.1111/j.1365-2699.2004...
). The Stockholm Paradigm thus identifies a critical, but simple role for climate change in the evolution of emerging diseases. Disease emergence occurs when pathogens are given the opportunity to explore more widely in fitness space based on pre-existing specific, yet phylogenetically conservative traits. In today’s world, such opportunities are being provided not only by the current episode of climate change, but also by increasing population density and hyper-connectivity of an increasing urbanized technological humanity.

Anticipate to Mitigate

The most effective time to mitigate the impacts of emerging disease is during the ecological fitting phase, when pathogens are expanding their geographical distributions and host ranges according to pre-existing (and thus predictable) capacities. The DAMA protocol (Brooks et al. 2019Brooks DR, Hoberg EP, Boeger WA (2019) The Stockholm Paradigm: Climate Change and Emerging Disease. University of Chicago Press, Chicago., 2014Brooks DR, Hoberg EP, Boeger WA, Gardner SL, Galbreath KE, Herczeg D, Mejia-Madrid HH, Racz SE, Dursahinhan AT (2014) Finding Them Before They Find Us: Informatics, Parasites, and Environments in Accelerating Climate Change. Comparative Parasitology 81: 155-164. https://doi.org/10.1654/4724b.1
https://doi.org/10.1654/4724b.1...
) is based on this principle.

We know many of the capacities of the virus, which allows us to anticipate what it could be doing now and could do in the future: (1) spread geographically gradually with climate change migration, rapidly with human assistance; (2) spread among host species by mosquitos; (3) spread within hosts by sexual transmission; and (4) cause damage to fetuses and neurological problems in all infected people.

Mitigating the damage caused by Zika means mitigating transmission. This can occur (in order of increasing cost) through protected sex; through screening both partners before conception; and by massive screening of all men and women, in countries where ZIKV is known to exist (to mitigate the next outbreak) and in countries where it is not yet known to exist (to mitigate its introduction and spread). As an emergent STD, Zika is just the most recent reminder of the significance of protected sex. Regular screenings, identical to those applied for the diagnosis of Herpes, HIV, Chlamydia and many other STDs should also screen for ZIKV, and public attention should be drawn to the elevated likelihood of acquiring Zika through intimate relationships.

These efforts will not eradicate the virus. They will help us buy time, postponing and mitigating the spread and impact of the next outbreak. During that time, we need to be assessing the possible connection between Zika and infertility. Viral infections are not considered major causes of such health problems, despite a large body of evidence of their capabilities in that regard. For example, immune reaction against trophoblasts can result in miscarriage or stillbirth. In line with these predictions, sexually transmitted viruses have already been demonstrated to terminate pregnancy at an early stage (Apari et al. 2014Apari P, de Sousa JD, Muller V (2014) Why Sexually Transmitted Infections Tend to Cause Infertility: An Evolutionary Hypothesis. Plos Pathogens 10: 5. https://doi.org/10.1371/journal.ppat.1004111
https://doi.org/10.1371/journal.ppat.100...
). Szaba et al (2018Szaba FM, Tighe M, Kummer LW, Lanzer KG, Ward JM, Lanthier P, Kim IJ, Kuki A, Blackman MA, Thomas SJ, Lin JS (2018) Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection. Plos Pathogens 14: 26. https://doi.org/10.1371/journal.ppat.1006994
https://doi.org/10.1371/journal.ppat.100...
) found that ZIKV causes most developmental damage by inducing cross-immunity in the early stages of pregnancy. During embryonic development, the anti-tumor Type I interferon (IFN) is impaired to protect trophoblasts exhibiting tumor-like characteristics (Budhwani et al. 2018Budhwani M, Mazzieri R, Dolcetti R (2018) Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti-tumor Immunity to Resistance. Frontiers in Oncology 8: 16. https://doi.org/10.3389/fonc.2018.00322
https://doi.org/10.3389/fonc.2018.00322...
, Soundararajan and Jagannadha Rao 2004Soundararajan R, Jagannadha Rao A (2004) Trophoblast ‘pseudo-tumorigenesis’: Significance and contributory factors. Reproductive Biology and Endocrinology 2: PMC407853. https://doi.org/10.1186/1477-7827-2-15
https://doi.org/10.1186/1477-7827-2-15...
). Exposure to Zika reactivated IFN and triggered an immune reaction against the trophoblasts. As well, recent studies showed that the suppression of the interferon response also enables ZIKV to increase fibroblast growth factor expression, thereby enhancing spread of the virus to fetal glial cells and neurons (Limonta et al. 2019Limonta D, Jovel J, Kumar A, Lu J, Hou S, Airo AM, Lopez-Orozco J, Wong CP, Saito L, Branton W, Wong GK, Mason A, Power C, Hobman TC (2019) Fibroblast growth factor 2 enhances Zika virus infection in human fetal brain. Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiz073
https://doi.org/10.1093/infdis/jiz073...
). Apart from causing neural damage, the virus has the potential to cause infertility. We suggest analyzing rates of miscarriages and stillbirths in affected areas before and after the outbreak. Female ZIKV patients should be monitored for spontaneous abortions or infertility issues.

The evolutionary story of ZIKV is fascinating, and the virus has become an important emergent pathogen. Strip away the unique details of this particular virus, however, and we find that ZIKV has been engaged in evolutionary business as usual for pathogens experiencing climate change events. That any pathogen can use climate change events to the extent allowed by their pre-existing capacities is a given. That those explorations of new connections in fitness space will lead to unanticipated innovations is also a given.

The alarming rise in microcephaly cases attracted international attention, because the symptoms of early neural-damage were easily noticeable. But other aspects of the pathogen’s pathology are far less conspicuous. Zika continues to exist in areas where it has been reported previously and has increased its geographic range since the 2015 outbreak in South America. With the recognition that Zika is a significant STD risk, with more than 80% of infected humans being asymptomatic, and with non-human vertebrate hosts being added to ZIKA’s host range, we must use this as a teachable moment about the potential impacts of business as usual for pathogen evolution during periods of climate change perturbations (Brooks et al. 2019Brooks DR, Hoberg EP, Boeger WA (2019) The Stockholm Paradigm: Climate Change and Emerging Disease. University of Chicago Press, Chicago.).

ACKNOWLEDGEMENTS

We thank Eörs Szathmáry for his support and valuable contributions to the study. We also thank the Economic Development and Innovation Operational Programme (GINOP 2.3.2-15-2016-00057) for providing funding for the study. Funder website: https://www.palyazat.gov.hu/evaluation

LITERATURE CITED

  • Agosta SJ (2006) On ecological fitting, plant-insect associations, herbivore host shifts, and host plant selection. Oikos 114: 556-565. https://doi.org/10.1111/j.2006.0030-1299.15025.x
    » https://doi.org/10.1111/j.2006.0030-1299.15025.x
  • Agosta SJ, Janz N, Brooks DR (2010) How specialists can be generalists: resolving the “parasite paradox” and implications for emerging infectious disease. Zoologia 27: 151-162. https://doi.org/10.1590/s1984-46702010000200001
    » https://doi.org/10.1590/s1984-46702010000200001
  • Agosta SJ, Klemens JA (2008) Ecological fitting by phenotypically flexible genotypes: implications for species associations, community assembly and evolution. Ecology Letters 11: 1123-1134. https://doi.org/10.1111/j.1461-0248.2008.01237.x
    » https://doi.org/10.1111/j.1461-0248.2008.01237.x
  • Ahmad F, Siddiqui A, Kamal MA, Sohrab SS (2018) Inhibition of Neurogenesis by Zika Virus Infection. Cns & Neurological Disorders-Drug Targets 17: 78-86. https://doi.org/10.2174/1871527317666180202115114
    » https://doi.org/10.2174/1871527317666180202115114
  • Anderson RM, May RM (1982) Coevolution of hosts and parasites. Parasitology 85: 411-426. https://doi.org/10.1017/s0031182000055360
    » https://doi.org/10.1017/s0031182000055360
  • Annamalai AS, Pattnaik A, Sahoo BR, Muthukrishnan E, Natarajan SK, Steffen D, Vu HLX, Delhon G, Osorio FA, Petro TM, Xiang SH, Pattnaik AK (2017) Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated and Defective in Neuroinvasion. Journal of Virology 91: 16. https://doi.org/10.1128/jvi.01348-17
    » https://doi.org/10.1128/jvi.01348-17
  • Apari P, de Sousa JD, Muller V (2014) Why Sexually Transmitted Infections Tend to Cause Infertility: An Evolutionary Hypothesis. Plos Pathogens 10: 5. https://doi.org/10.1371/journal.ppat.1004111
    » https://doi.org/10.1371/journal.ppat.1004111
  • Araujo SBL, Braga MP, Brooks DR, Agosta SJ, Hoberg EP, von Hartenthal FW, Boeger WA (2015) Understanding Host-Switching by Ecological Fitting. Plos One 10: 17. https://doi.org/10.1371/journal.pone.0139225
    » https://doi.org/10.1371/journal.pone.0139225
  • Audy JR (1958) The localization of disease with special reference to the zoonoses. Transactions of the Royal Society of Tropical Medicine and Hygiene 52: 309-328. https://doi.org/10.1016/0035-9203(58)90045-2
    » https://doi.org/10.1016/0035-9203(58)90045-2
  • Barzon L, Pacenti M, Franchin E, Lavezzo E, Trevisan M, Sgarabotto D, Palu G (2016) Infection dynamics in a traveller with persistent shedding of Zika virus RNA in semen for six months after returning from Haiti to Italy, January 2016. Eurosurveillance 21: 2-5. https://doi.org/10.2807/1560-7917.es.2016.21.32.30316
    » https://doi.org/10.2807/1560-7917.es.2016.21.32.30316
  • Beaver JT, Lelutiu N, Habib R, Skountzou I (2018) Evolution of Two Major Zika Virus Lineages: Implications for Pathology, Immune Response, and Vaccine Development. Frontiers in Immunology 9: 17. https://doi.org/10.3389/fimmu.2018.01640
    » https://doi.org/10.3389/fimmu.2018.01640
  • Braga MP, Araujo SBL, Agosta S, Brooks D, Hoberg E, Nylin S, Janz N, Boeger WA (2018) Host use dynamics in a heterogeneous fitness landscape generates oscillations in host range and diversification. Evolution 72: 1773-1783. https://doi.org/10.1111/evo.13557
    » https://doi.org/10.1111/evo.13557
  • Brooks DR, Boeger WA (2019) Climate change and emerging infectious diseases: Evolutionary complexity in action. Current Opinion in Systems Biology 13: 75-81. https://doi.org/10.1016/j.coisb.2018.11.001
    » https://doi.org/10.1016/j.coisb.2018.11.001
  • Brooks DR, Hoberg EP, Boeger WA (2019) The Stockholm Paradigm: Climate Change and Emerging Disease. University of Chicago Press, Chicago.
  • Brooks DR, Hoberg EP, Boeger WA, Gardner SL, Galbreath KE, Herczeg D, Mejia-Madrid HH, Racz SE, Dursahinhan AT (2014) Finding Them Before They Find Us: Informatics, Parasites, and Environments in Accelerating Climate Change. Comparative Parasitology 81: 155-164. https://doi.org/10.1654/4724b.1
    » https://doi.org/10.1654/4724b.1
  • Brooks DR, Leon-Regagnon V, McLennan DA, Zelmer D (2006) Ecological fitting as a determinant of the community structure of platyhelminth parasites of anurans. Ecology 87: S76-S85. https://doi.org/10.1890/0012-9658(2006)87[76:efaado]2.0.co;2
    » https://doi.org/10.1890/0012-9658(2006)87[76:efaado]2.0.co;2
  • Brooks DR, McLennan DA (2002) The nature of diversity: an evolutionary voyage of discovery. University of Chigaco Press, Chicago, Illinois.
  • Budhwani M, Mazzieri R, Dolcetti R (2018) Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti-tumor Immunity to Resistance. Frontiers in Oncology 8: 16. https://doi.org/10.3389/fonc.2018.00322
    » https://doi.org/10.3389/fonc.2018.00322
  • Chakhtoura N, Hazra R, Spong CY (2018) Zika virus: a public health perspective. Current Opinion in Obstetrics & Gynecology 30: 116-122. https://doi.org/10.1097/gco.0000000000000440
    » https://doi.org/10.1097/gco.0000000000000440
  • Cohen J (2018) Infectious disease steep drop in Zika cases undermines vaccine trial. Science 361: 1055-1056. https://doi.org/10.1126/science.361.6407.1055
    » https://doi.org/10.1126/science.361.6407.1055
  • Darwin C (1872) The origin of species. Murray, London.
  • Dick GWA (1952) Zika virus (II). Pathogenicity and physical properties. Transactions of the Royal Society of Tropical Medicine and Hygiene 46: 521-534. https://doi.org/10.1016/0035-9203(52)90043-6
    » https://doi.org/10.1016/0035-9203(52)90043-6
  • Dodson BL, Pujhari S, Rasgon JL (2018) Vector competence of selected North American Anopheles and Culex mosquitoes for Zika virus. Peerj 6: 10. https://doi.org/10.7717/peerj.4324
    » https://doi.org/10.7717/peerj.4324
  • Dudley DM, Aliota MT, Mohr EL, Weiler AM, Lehrer-Brey G, Weisgrau KL, Mohns MS, Breitbach ME, Rasheed MN, Newman CM, Gellerup DD, Moncla LH, Post J, Schultz-Darken N, Schotzko ML, Hayes JM, Eudailey JA, Moody MA, Permar SR, O’Connor SL, Rakasz EG, Simmons HA, Capuano S, Golos TG, Osorio JE, Friedrich TC, O’Connor DH (2016) A rhesus macaque model of Asian-lineage Zika virus infection. Nature Communications 7: 9. https://doi.org/10.1038/ncomms12204
    » https://doi.org/10.1038/ncomms12204
  • Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, Pretrick M, Marfel M, Holzbauer S, Dubray C, Guillaumot L, Griggs A, Bel M, Lambert AJ, Laven J, Kosoy O, Panella A, Biggerstaff BJ, Fischer M, Hayes EB (2009) Zika Virus Outbreak on Yap Island, Federated States of Micronesia. New England Journal of Medicine 360: 2536-2543. https://doi.org/10.1056/NEJMoa0805715
    » https://doi.org/10.1056/NEJMoa0805715
  • Erwin TL (1981) Taxon Pulses, Vicariance, and Dispersal: An Evolutionary Synthesis illustrated by Carabid Beetles. In: Gareth NaDER (Ed) Vicariance Biogeography: A Critique. Columbia University Press, New York, 159-196.
  • Ewald PW (2004) Evolution of virulence. Infectious Disease Clinics of North America 18: 1-15. https://doi.org/10.1016/S0891-5520(03)00099-0
    » https://doi.org/10.1016/S0891-5520(03)00099-0
  • Ferdousi T, Cohnstaedt LW, McVey DS, Scoglio CM (2019) Understanding the survival of Zika virus in a vector interconnected sexual contact network. Scientific Reports 9: 7253. https://doi.org/10.1038/s41598-019-43651-3
    » https://doi.org/10.1038/s41598-019-43651-3
  • Foy BD, Kobylinski KC, Foy JLC, Blitvich BJ, da Rosa AT, Haddow AD, Lanciotti RS, Tesh RB (2011) Probable Non-Vector-borne Transmission of Zika Virus, Colorado, USA. Emerging Infectious Diseases 17: 880-882. https://doi.org/10.3201/eid1705.101939
    » https://doi.org/10.3201/eid1705.101939
  • Freour T, Mirallie S, Hubert B, Splingart C, Barriere P, Maquart M, Leparc-Goffart I (2016) Sexual transmission of Zika virus in an entirely asymptomatic couple returning from a Zika epidemic area, France, April 2016. Eurosurveillance 21: 10-12. https://doi.org/10.2807/1560-7917.es.2016.21.23.30254
    » https://doi.org/10.2807/1560-7917.es.2016.21.23.30254
  • Halas D, Zamparo D, Brooks DR (2005) A historical biogeographical protocol for studying biotic diversification by taxon pulses. Journal of Biogeography 32: 249-260. https://doi.org/10.1111/j.1365-2699.2004.01147.x
    » https://doi.org/10.1111/j.1365-2699.2004.01147.x
  • Hoberg EP, Brooks DR (2008) A macroevolutionary mosaic: episodic host-switching, geographical colonization and diversification in complex host-parasite systems. Journal of Biogeography 35: 1533-1550. https://doi.org/10.1111/j.1365-2699.2008.01951.x
    » https://doi.org/10.1111/j.1365-2699.2008.01951.x
  • Hoberg EP, Brooks DR (2015) Evolution in action: climate change, biodiversity dynamics and emerging infectious disease. Philosophical Transactions of the Royal Society B-Biological Sciences 370: 7. https://doi.org/10.1098/rstb.2013.0553
    » https://doi.org/10.1098/rstb.2013.0553
  • Janz N, Nylin S (2008) The Oscillation Hypothesis of Host-Plant Range and Speciation. In: Tilmon KJ (Ed) Specialization, Speciation, and Radiation: The Evolutionary Biology of Herbivorous Insects. Berkeley, University of California Press, 203-215.
  • Janz N, Nylin S, Wahlberg N (2006) Diversity begets diversity: host expansions and the diversification of plant-feeding insects. Bmc Evolutionary Biology 6: 10. https://doi.org/10.1186/1471-2148-6-4
    » https://doi.org/10.1186/1471-2148-6-4
  • Janzen DH (1985) On ecological fitting. Oikos 45: 308-310. https://doi.org/10.2307/3565565
    » https://doi.org/10.2307/3565565
  • Limonta D, Jovel J, Kumar A, Lu J, Hou S, Airo AM, Lopez-Orozco J, Wong CP, Saito L, Branton W, Wong GK, Mason A, Power C, Hobman TC (2019) Fibroblast growth factor 2 enhances Zika virus infection in human fetal brain. Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiz073
    » https://doi.org/10.1093/infdis/jiz073
  • May RM, Anderson RM (1983) Epidemiology and genetics in the coevolution of parasites and hosts. Proceedings of the Royal Society Series B-Biological Sciences 219: 281-313. https://doi.org/10.1098/rspb.1983.0075
    » https://doi.org/10.1098/rspb.1983.0075
  • Mendez N, Oviedo-Pastrana M, Mattar S, Caicedo-Castro I, Arrieta G (2017) Zika virus disease, microcephaly and Guillain-Barre syndrome in Colombia: epidemiological situation during 21 months of the Zika virus outbreak, 2015-2017. Archives of Public Health 75: 11. https://doi.org/10.1186/s13690-017-0233-5
    » https://doi.org/10.1186/s13690-017-0233-5
  • Mladinich MC, Schwedes J, Mackow ER (2017) Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells. Mbio 8: 17. https://doi.org/10.1128/mBio.00952-17
    » https://doi.org/10.1128/mBio.00952-17
  • Moreira J, Peixoto TM, Siqueira AM, Lamas CC (2017) Sexually acquired Zika virus: a systematic review. Clinical Microbiology and Infection 23: 296-305. https://doi.org/10.1016/j.cmi.2016.12.027
    » https://doi.org/10.1016/j.cmi.2016.12.027
  • Petersen LR, Jamieson DJ, Powers AM, Honein MA (2016) Zika Virus. New England Journal of Medicine 374: 1552-1563. https://doi.org/10.1056/NEJMra1602113
    » https://doi.org/10.1056/NEJMra1602113
  • Provine WB (2004) Ernst Mayr: genetics and speciation. Genetics 167: 1041-1046.
  • Roundy CM, Azar SR, Rossi SL, Huang JH, Leal G, Yun R, Fernandez-Salas I, Vitek CJ, Paploski IAD, Kitron U, Ribeiro GS, Hanley KA, Weaver SC, Vasilakis N (2017) Variation in Aedes aegypti Mosquito Competence for Zika Virus Transmission. Emerging Infectious Diseases 23: 625-632. https://doi.org/10.3201/eid2304.161484
    » https://doi.org/10.3201/eid2304.161484
  • Sakkas H, Bozidis P, Giannakopoulos X, Sofikitis N, Papadopoulou C (2018) An Update on Sexual Transmission of Zika Virus. Pathogens 7: 14. https://doi.org/10.3390/pathogens7030066
    » https://doi.org/10.3390/pathogens7030066
  • Silva JVJ, Lopes TRR, de Oliveira EF, Oliveira RAD, Gil L (2017) Perspectives on the Zika outbreak: herd immunity, antibodydependent enhancement and vaccine. Revista do Instituto de Medicina Tropical de São Paulo 59: 2. https://doi.org/10.1590/s1678-9946201759021
    » https://doi.org/10.1590/s1678-9946201759021
  • Simonin Y, van Riel D, de Perre PV, Rockx B, Salinas S (2017) Differential virulence between Asian and African lineages of Zika virus. Plos Neglected Tropical Diseases 11: 8. https://doi.org/10.1371/journal.pntd.0005821
    » https://doi.org/10.1371/journal.pntd.0005821
  • Smith DR, Sprague TR, Hollidge BS, Valdez SM, Padilla SL, Bellanca SA, Golden JW, Coyne SR, Kulesh DA, Miller LJ, Haddow AD, Koehler JW, Gromowski GD, Jarman RG, Alera MTP, Yoon IK, Buathong R, Lowen RG, Kane CD, Minogue TD, Bavari S, Tesh RB, Weaver SC, Linthicum KJ, Pitt ML, Nasar F (2018) African and Asian Zika Virus Isolates Display Phenotypic Differences Both In Vitro and In Vivo. American Journal of Tropical Medicine and Hygiene 98: 432-444. https://doi.org/10.4269/ajtmh.17-0685
    » https://doi.org/10.4269/ajtmh.17-0685
  • Soundararajan R, Jagannadha Rao A (2004) Trophoblast ‘pseudo-tumorigenesis’: Significance and contributory factors. Reproductive Biology and Endocrinology 2: PMC407853. https://doi.org/10.1186/1477-7827-2-15
    » https://doi.org/10.1186/1477-7827-2-15
  • Szaba FM, Tighe M, Kummer LW, Lanzer KG, Ward JM, Lanthier P, Kim IJ, Kuki A, Blackman MA, Thomas SJ, Lin JS (2018) Zika virus infection in immunocompetent pregnant mice causes fetal damage and placental pathology in the absence of fetal infection. Plos Pathogens 14: 26. https://doi.org/10.1371/journal.ppat.1006994
    » https://doi.org/10.1371/journal.ppat.1006994
  • Thompson JN (1994) The coevolutionary process. University of Chicago, Chicago.
  • Vianna P, Gomes JD, Boquett JA, Fraga LR, Schuch JB, Vianna FSL, Schuler-Faccini L (2018) Zika Virus as a Possible Risk Factor for Autism Spectrum Disorder: Neuroimmunological Aspects. Neuroimmunomodulation 25: 320-327. https://doi.org/10.1159/000495660
    » https://doi.org/10.1159/000495660
  • Walker CL, Little MTE, Roby JA, Armistead B, Gale M, Rajagopal L, Nelson BR, Ehinger N, Mason B, Nayeri U, Curry CL, Waldorf KMA (2019) Zika virus and the nonmicrocephalic fetus: why we should still worry. American Journal of Obstetrics and Gynecology 220: 45-56. https://doi.org/10.1016/j.ajog.2018.08.035
    » https://doi.org/10.1016/j.ajog.2018.08.035
  • Wolfe ND, Dunavan CP, Diamond J (2007) Origins of major human infectious diseases. Nature 447: 279-283. https://doi.org/10.1038/nature05775
    » https://doi.org/10.1038/nature05775

Publication Notes

  • Available online:

    November 26, 2019
  • Publisher:

    © 2019 Sociedade Brasileira de Zoologia. Published by Pensoft Publishers at https://zoologia.pensoft.net

Edited by

Editorial responsibility:

Sionei R. Bonatto

Publication Dates

  • Publication in this collection
    05 Dec 2019
  • Date of issue
    2019

History

  • Received
    25 May 2019
  • Accepted
    28 June 2019
  • Published
    26 Nov 2019
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