Novel variants of human herpesvirus 2 from Brazilian HIV-1 coinfected subjects

BACKGROUND Human herpesvirus 2 (HHV-2) have DNA genome with a limited genetic variability and have been classified into two clades. OBJECTIVES To identify and characterise six HHV-2 isolates derived from Brazilian women. METHODS HHV-2 isolates were performed polymerase chain reaction (PCR) and sequencing of 2250 pb of the glycoprotein B (gB) coding regions. FINDINGS Four HHV-2 isolates were classified into clade B, while the remaining two, derived from HIV-1 co-infected women, showed a notable genetic divergence (> 1%). MAIN CONCLUSION The results reveal novel HHV-2 variants. The impact of these novel variants on HHV-2 pathogenesis and HIV/HHV-2 coinfection need to be investigated.

Key words:
Brazil; clade; co-infection; glycoprotein B; HSV-2; HIV

Authorship

Lyana Rodrigues Pinto Lima

Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Virologia Molecular, Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz-FiocruzBrazilRio de Janeiro, RJ, BrazilFundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Virologia Molecular, Rio de Janeiro, RJ, Brasil

Nathália Alves de Araújo

Alexandro Guterres

Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hantaviroses e Rickettsioses, Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz-FiocruzBrazilRio de Janeiro, RJ, BrazilFundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hantaviroses e Rickettsioses, Rio de Janeiro, RJ, Brasil

José Henrique Pilotto

Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de AIDS e Imunologia Molecular, Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz-FiocruzBrazilRio de Janeiro, RJ, BrazilFundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de AIDS e Imunologia Molecular, Rio de Janeiro, RJ, Brasil

Hospital Geral, Nova Iguaçu, RJ, BrasilHospital GeralBrasilNova Iguaçu, RJ, BrasilHospital Geral, Nova Iguaçu, RJ, Brasil

Christian Niel

Vanessa Salete de Paula ⁺+ Corresponding author: vdepaula@ioc.fiocruz.br

+ Corresponding author: vdepaula@ioc.fiocruz.br

Lima wrote this article and performed the laboratorial tests; Araújo performed the laboratorial tests; Guterres performed the phylogenetic analyse; Pilotto collected the blood samples; Niel and de Paula revised the article.

SCIMAGO INSTITUTIONS RANKINGS

Hospital Geral, Nova Iguaçu, RJ, BrasilHospital GeralBrasilNova Iguaçu, RJ, BrasilHospital Geral, Nova Iguaçu, RJ, Brasil

Figures | Tables

Figures (1)
Tables (2)

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Phylogenetic relationships
among human herpesvirus 2 (HHV-2) based on Bayesian analysis of genetic distances generated from comparisons of a 2,250-bp fragment of the glycoprotein B (gB) sequences. The scale bar indicates an evolutionary distance of 0.003 substitutions per position. Numerical values (≥ 0.7) at the nodes indicate posterior probability replicates that supported by the interior branch. The Tamura 3-parameter model with gamma-distributed rate heterogeneity (T92 + G) was selected as the best-fit evolutionary model. Clades A and B are in accordance with previous studies.⁸8. Norberg P, Kasubi MJ, Haarr L, Bergström T, Liljeqvist JA. Divergence and recombination of clinical herpes simplex virus type 2 isolates. J Virol. 2007; 81(23): 13158-67.^,⁹9. Schmidt-Chanasit J, Bialonski A, Heinemann P, Ulrich RG, Günther S, Rabenau HF, et al. A 12-year molecular survey of clinical herpes simplex virus type 2 isolates demonstrates the circulation of clade A and B strains in Germany. J Clin Virol. 2010; 48(3): 208-11.

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TABLE I
Oligonucleotide primers used in this study

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TABLE II
Specific mutations found in the glycoprotein B (gB) coding regions of two human herpesvirus 2 (HHV-2) isolates derived from Brazilian HIV co-infected women

Phylogenetic relationships among human herpesvirus 2 (HHV-2) based on Bayesian analysis of genetic distances generated from comparisons of a 2,250-bp fragment of the glycoprotein B (gB) sequences. The scale bar indicates an evolutionary distance of 0.003 substitutions per position. Numerical values (≥ 0.7) at the nodes indicate posterior probability replicates that supported by the interior branch. The Tamura 3-parameter model with gamma-distributed rate heterogeneity (T92 + G) was selected as the best-fit evolutionary model. Clades A and B are in accordance with previous studies.⁸8. Norberg P, Kasubi MJ, Haarr L, Bergström T, Liljeqvist JA. Divergence and recombination of clinical herpes simplex virus type 2 isolates. J Virol. 2007; 81(23): 13158-67.^,⁹9. Schmidt-Chanasit J, Bialonski A, Heinemann P, Ulrich RG, Günther S, Rabenau HF, et al. A 12-year molecular survey of clinical herpes simplex virus type 2 isolates demonstrates the circulation of clade A and B strains in Germany. J Clin Virol. 2010; 48(3): 208-11.

TABLE I Oligonucleotide primers used in this study

Primer	Genome position^*	Sequence (5´ → 3´)	Reference
gB1 For		CCCATCCCCTCGAAGAAC	Abrão et al.⁽¹⁹⁾
gB1 Rev	577	CAGACCCCCTTGGCGTTAAT	This study
gB2 For	424	TTCAAGGAGAACATCGCCCC	This study
gB2 Rev	744	GGGGTTGTACTTGAGGTCGG	This study
gB3 For	557	ATTAACGCCAAGGGGGTCTG	This study
gB3 Rev	885	GTAGCCGTAAAACGGGGACA	This study
gB4 For	725	CCGACCTCAAGTACAACCCC	This study
gB4 Rev	1164	GGTGAAGGTGGTCGAGATGG	This study
gB5 For	1008	GCTGACGACCCCAAGTTTA	This study
gB5 Rev	1487	TCGATCGAGGAGGTGGTCTT	This study
gB6 For	1158	CCTTCACCACCAACCTGACC	This study
gB6 Rev	1532	CGTGGCGCTGTATGTGGTTA	This study
gB7 For	1464	GCATCAAGACCACCTCCTCG	This study
gB7 Rev	1912	GAAGATGAAGTAGCGCCGGT	This study
gB8 For	1604	CGAGCTGACTCTCTCGGAACG	This study
gB8 Rev	2035	CACAAACTCGTGGTCCTCCA	This study
gB9 For	1916	GGGGCTACGTGTACTTCGAG	This study
gB9 Rev	2410	ACAGGGCCTTCATGGGATTG	This study
gB10 For	2391	CAATCCCATGAAGGCCCTGT	This study
gB10 Rev	2606	GTTGGTGACCTTGGAGCTGA	This study

*: numbering from the initiation codon of the glycoprotein B (gB) coding region.

TABLE II Specific mutations found in the glycoprotein B (gB) coding regions of two human herpesvirus 2 (HHV-2) isolates derived from Brazilian HIV co-infected women

Nucleotide change^a	Presence in ChHV prototype^b	Amino acid change
G1254C	No	-
C1323G	No	-
G1411C	No	A471P
C1617G	No	-
C1668G	No	-
C1683G	No	-
G1731C	No	-
G1734A	Yes	-
G1747A	No	V583I
G1761C	Yes	-
G1767C	No	-
C1816T	Yes	-
C1836G	No	-
C1857G	No	-
G1972A	Yes	-
G2001C	No	-

a: numbering from the initiation codon of the gB coding region; b: number access of chimpanzee alphaherpesvirus (ChHV) prototype: NC_023677.1.

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[1] + Corresponding author: vdepaula@ioc.fiocruz.br