SciELO - Scientific Electronic Library Online

vol.30 issue1Clinical and radiographic sequelae to primary teeth affected by dental trauma: a 9-year retrospective studyFluoride rinse effect on retention of CaF2 formed on enamel/dentine by fluoride application author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand




Related links


Brazilian Oral Research

Print version ISSN 1806-8324On-line version ISSN 1807-3107

Braz. oral res. vol.30 no.1 São Paulo  2016  Epub Mar 15, 2016 

Short Communication

Zika virus infection spread through saliva – a truth or myth?

Walter Luiz SIQUEIRA(a) 

Eduardo Buozi MOFFA(a) 

Maria Carolina Martins MUSSI(b) 

Maria Aparecida de Andrade Moreira MACHADO(c) 

(a)University of Western Ontario, Schulich School of Medicine & Dentistry, Department of Dentistry and Biochemistry, London, ON, Canada.

(b) Universidade de São Paulo - USP, School of Dentistry, Department of Oral Pathology, São Paulo, SP, Brazil.

(c)Universidade de São Paulo - USP, Bauru Dental School, Department of Pediatric Dentistry, Orthodontics and Public Health, Bauru, SP, Brazil.


In this Point-of-view article we highlighted some features related to saliva and virus infection, in special for zika virus. In addition, we pointed out the potential oral problems caused by a microcephaly originated by a zika virus infection. In the end the, we demonstrated the importance of a more comprehensive exploration of saliva and their components as a fluid for diagnostic and therapeutic approaches on oral and systemic diseases.

Key words: Saliva; Zika Virus; Microcephaly; Pediatric Dentistry; Infection; Pediatrics


Recent finds shown the presence of zika virus (ZIKV) in blood, semen, urine and saliva, suggesting that the transmission could be also by these corporal fluids.1,2 However, until now, there is no any scientific evidence to support that the infection of ZIKV could be through human saliva. Besides the detection of ZIKV in saliva was reported for a neonate and his/her mother, respectively, on days 3 and 2 post partum.3 A recent report case evidenced the ZIKV presence in a fetus with microcephaly. The authors reported the ZIKV isolation by reverse transcription polymerase chain reaction assay from the fetal brain tissue. According to the Brazilian Ministry of Health in 2015 more than 1,2 million cases of dengue and 9,000 cases of Zika were officially reported in Brazil. In addition, the total numbers of Zika cases related to microcephaly in newborn are almost 3,000 with an estimation of 200 new cases reported every month.3 We can speculate that in the near future, the increasing number of microcephaly associated with ZIKV will significantly affect not only the general health status of their patients, but also the dental care cost in those countries affected by these conditions. Our hypothesis is based on several clinical features associated with microcephaly, such as late closure of the fontanel, characteristic facial appearance with down-slanting palpebral fissures, midfacial hypoplasia, short nose, small mouth and, in some of the children, joint anomalies (congenital hip dislocation, joint laxity and pes planus), muscle hypotonia, down-slanting palpebral fissures and mental retardation4 could be present in these children. This is a considerable problem for public health in countries with the ZIKV epidemic and Brazil is one of these countries. The need for a multidisciplinary team to treat these patients has a direct impact on the high cost of treatment. It should also be considered the social impact on families of these patients, as they need to be monitored all day.

In relation to saliva and virus presence, there are some viral infectious diseases that can be transmitted by saliva, such as cytomegalovirus and hepatitis (hepatitis B). However many viral infections ( e.g. dengue) are present in saliva, but not transmitted by saliva. For example, despite the presence of HIV in saliva,5 there have never been any reports of HIV transmission via this route. In this regard, HIV infection can be detected by saliva using a fast, and simple point-of-care detection test called OraQuick®. This “in-home test” is FDA-approved and presented a sensitivity and specificity higher than 98%,6 which is statistically similar to the classical ELISA test carried out in laboratory to detect HIV infection. Saliva has important properties enabling its use as a diagnostic tool for viral diseases.7 Besides the virus presence in saliva, some viruses ( e.g. HCV), exhibit a direct correlation between viral load in and the presence of virus in saliva.6,8 Despite the virus presence in saliva, many viruses cannot infect the host ( e.g. HIV), highlighting the possible saliva role in modulating viral infection.9,10 For HIV, the saliva contains many components that decrease the virus infectivity. There is evidence from studies with HIV virus, showing that saliva proteins can act at different stages of the infection cycle, since the complexes formation between macromolecules, viruses and antiviral proteins to the direct antiviral capacity or inhibiting virus invasion to susceptible cells.11 The antiviral activity can be attributed to both the parotid saliva as the submandibular/sublingual saliva.11,12 MUC5B and proteins related to scavenger receptors have activity against several viruses, such as HIV and influenza viruses. Other proteins do not have a well-established viral activity. Lactoferrin and histatins showed antiviral activity to HIV but not to and influenza viruses. The MUC5B can exert antiviral activity by virus aggregation and entrapment. The MUC5B function has been assigned to multivalent negative charge presence of the sialic acid or sulphated residues.11,12 Nevertheless, the neuraminidase enzyme might play cleavage of sialic acid and gradually inactivate this protein for influenza viruses.12

In our point-of-view, the presence of ZIKV in saliva highlights the relevance of the use of saliva as a diagnostic tool. In this manner, in the recent years, saliva is becoming more recognized as a diagnostic fluid not only because of its multiple contributors such as serum and oral cell debris, but also because sampling is noninvasive, easy to obtain, painless and low cost.13 Moreover, due to the fast emerging high-sensitive biotechnologies such as ELISA multiplex and mass spectrometry technology more prominent studies are underway using saliva for the identification of biomarkers for various diseases such as breast, ovarian, hepatocellular and oral cancers as well as leukoplakia and Sjogren’s syndrome.14 For example, we have recently shown correlation between end-stage renal disease and salivary nitrite and uric acid concentrations by using a colorimetric test strips.15

The proof-of-principle has been extended and we have also shown a strong correlation between 10 cytokines present in saliva and pulmonary disease, such as asthma, using a microsphere-based antibody array.16 Therefore, we postulate that these new high-sensitive technologies able to measure multiples salivary biomarkers simultaneously, could become clinical tools for early detection and monitoring of prognosis and treatment for other diseases, including dengue and Zika infections.17 Now that researchers around the world are committed to seek ways to eradicate ZIKV, all efforts in this direction should be considered. Early diagnosis using safe and non-invasive methods for ZIKV allow therapeutic measures are taken faster with less discomfort for the patient is part of this task force against this disease.

Therefore, search for a diagnostic test for ZIKA virus, as well as other viral infections as dengue and chikungunya virus in saliva is a route that should be considered.


Supported by The Canadian Institutes of Health Research CIHR grants #106657, #97577, and Canada Foundation for Innovation grant #25116. WLS is recipient of a CIHR New Investigator Award grant#113166.


1. Mizuno Y, Kotaki A, Harada F, Tajima S, Kurane I, Takasaki T. Confirmation of dengue virus infection by detection of dengue virus type 1 genome in urine and saliva but not in plasma. Trans R Soc Trop Med Hyg. 2007;101(7):738-9. doi:10.1016/j.trstmh.2007.02.007 [ Links ]

2. Poloni TR, Oliveira AS, Alfonso HL, Galvão LR, Amarilla AA, Poloni DF, et al. Detection of dengue virus in saliva and urine by real time RT-PCR. Virol J. 2010;7(1):22. doi:10.1186/1743-422X-7-22 [ Links ]

3. Besnard M, Lastere S, Teissier A, Cao-Lormeau V, Musso D. Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014. Euro Surveill. 2014 Apr 3;19(13). pii: 20751. doi:10.2807/1560-7917.ES2014.19.13.20751 [ Links ]

4. Morava E, Lefeber DJ, Urban Z, de Meirleir L, Meinecke P, Gillessen Kaesbach G, et al. Defining the phenotype in an autosomal recessive cutis laxa syndrome with a combined congenital defect of glycosylation. Eur J Hum Genet. 2008;16(1):28-35. doi:10.1038/sj.ejhg.5201947 [ Links ]

5. Archibald DW, Zon L, Groopman JE, McLane MF, Essex M. Antibodies to human T-lymphotropic virus type III (HTLV-III) in saliva of acquired immunodeficiency syndrome (AIDS) patients and in persons at risk for AIDS. Blood. 1986;67(3):831-4. [ Links ]

6. Hermida M, Ferreiro MC, Barral S, Laredo S, Castro A, Diz Dios P. Detection of HCV RNA in saliva of patients with hepatitis C virus infection by using a highly sensitive test. J Virol Methods. 2002 Mar;101(1-2):29-35. doi:10.1016/S0166-0934(01)00417-7 [ Links ]

7. Corstjens PLAM, Abrams WR, Malamud D. Saliva and viral infections. Periodontol 2000. 2016;70(1):93-110. doi:10.1111/prd.12112 [ Links ]

8. Ferreiro MC, Dios PD, Scully C. Transmission of hepatitis C virus by saliva? Oral Dis. 2005;11(4):230-5. doi:10.1111/j.1601-0825.2005.01076.x [ Links ]

9. Liuzzi G, Chirianni A, Clementi M, Bagnarelli P, Valenza A, Cataldo PT, et al. Analysis of HIV-1 load in blood, semen and saliva: evidence for different viral compartments in a cross-sectional and longitudinal study. AIDS. 1996;10(14):F51-6. doi:10.1097/00002030-199612000-00001 [ Links ]

10. Baron S, Poast J, Cloyd MW. Why is HIV rarely transmitted by oral secretions? Saliva can disrupt orally shed, infected leukocytes. Arch Intern Med. 2016;159(3):303-10. doi:10.1001/archinte.159.3.303 [ Links ]

11. Bolscher JG, Nazmi K, Ran LJ, van Engelenburg FA, Schuitemaker H, Veerman EC, et al. Inhibition of HIV-1 IIIB and clinical isolates by human parotid, submandibular, sublingual and palatine saliva. Eur J Oral Sci. 2002;110(2):149-56. doi:10.1034/j.1600-0722.2002.11175.x [ Links ]

12. White MR, Helmerhorst EJ, Ligtenberg A, Karpel M, Tecle T, Siqueira WL et al. Multiple components contribute to ability of saliva to inhibit influenza viruses. Oral Microbiol Immunol. 2009;24(1):18-24. doi:10.1111/j.1399-302X.2008.00468.x [ Links ]

13. Siqueira WL, Dawes C. The salivary proteome: challenges and perspectives. Proteomics Clin Appl. 2011;5(11-12):575-9. doi:10.1002/prca.201100046 [ Links ]

14. Lee YH, Wong DT. Saliva: an emerging biofluid for early detection of diseases. Am J Dent. 2009;22(4):241-8. [ Links ]

15. Blicharz TM, Rissin DM, Bowden M, Hayman RB, DiCesare C, Bhatia JS, et al. Use of colorimetric test strips for monitoring the effect of hemodialysis on salivary nitrite and uric acid in patients with end-stage renal disease: a proof of principle. Clin Chem. 2008;54(9):1473-80. doi:10.1373/clinchem.2008.105320 [ Links ]

16. Blicharz TM, Siqueira WL, Helmerhorst EJ, Oppenheim FG, Wexler PJ, Little FF, et al. Fiber-optic microsphere-based antibody array for the analysis of inflammatory cytokines in saliva. Anal Chem 2009 Mar;81(6):2106–14. doi:10.1021/ac802181j [ Links ]

17. Mussoa D, Rocheb C, Nhana T, Robina E, Teissierb A, Cao-Lormeaub V. Detection of Zika virus in saliva. J Clin Virol. 2015;68:50-3. doi:10.1016/j.jcv.2015.04.021 [ Links ]

Received: February 13, 2016; Revised: February 19, 2016; Accepted: February 22, 2016

Corresponding Author: Walter Luiz Siqueira.

Declaration of Interests: The authors certify that they have no commercial or associative interest that represents a conflict of interest in connection with the manuscript.

Creative Commons License This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.