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J Virol. 2019 Jun 14;93(13). pii: e01769-18. doi: 10.1128/JVI.01769-18. Print 2019 Jul 1.

Comparisons of Human Immunodeficiency Virus Type 1 Envelope Variants in Blood and Genital Fluids near the Time of Male-to-Female Transmission.

Author information

1
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.
2
Department of Medicine, University of Washington, Seattle, Washington, USA.
3
Department of Microbiology, University of Washington, Seattle, Washington, USA.
4
Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
5
Department of Epidemiology, University of Washington, Seattle, Washington, USA.
6
Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Institute, Seattle, Washington, USA.
7
Department of Molecular Medicine and Haematology, University of Witwatersrand, Johannesburg, South Africa.
8
Contract Laboratory Services, University of Witwatersrand, Johannesburg, South Africa.
9
Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
10
Department of Global Health, University of Washington, Seattle, Washington, USA.
11
Reproductive Health & HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
12
Department of Medicine, University of Washington, Seattle, Washington, USA lingappa@uw.edu lfrenkel@uw.edu.
13
Department of Pediatrics, University of Washington, Seattle, Washington, USA.
14
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA lingappa@uw.edu lfrenkel@uw.edu.

Abstract

To better understand the transmission of human immunodeficiency virus type 1 (HIV-1), the genetic characteristics of blood and genital viruses from males were compared to those of the imputed founding virus population in their female partners. Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genital specimens collected near the time of transmission were studied. Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 env gp160. Eight of 29 couples examined yielded viral sequences from both tissues. Analysis of these couples' sequences demonstrated, with one exception, that the women's founding viral populations arose from a single viral variant and were CCR5 tropic, even though CXCR4 variants were detected within four males. The median genetic distance of the imputed most recent common ancestor of the women's founder viruses showed that they were closer to the semen viruses than to the blood viruses of their transmitting male partner, but this finding was biased by detection of a greater number of viral clades in the blood. Using multiple assays, the blood and genital viruses were consistently found to be compartmentalized in only two of eight men. No distinct amino acid signatures in the men's viruses were found to link to the women's founders, nor did the women's env sequences have shorter variable loops or fewer N-linked glycosylation sites. The lack of selective factors, except for coreceptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions. The infrequent compartmentalization between the transmitters' blood and semen viruses suggests that cell-free blood virus likely includes HIV-1 sequences representative of those of viruses in semen.IMPORTANCE Mucosal transmissions account for the majority of HIV-1 infections. Identification of the viral characteristics associated with transmission would facilitate vaccine design. This study of HIV strains from transmitting males and their seroconverting female partners found that the males' genital tract viruses were rarely distinct from the blood variants. The imputed founder viruses in women were genetically similar to both the blood and genital tract variants of their male partners, indicating a lack of evidence for genital tract-specific lineages. These findings suggest that targeting vaccine responses to variants found in blood are likely to also protect from genital tract variants.

KEYWORDS:

HIV; N-linked glycosylation; coreceptor usage; genetic bottleneck; heterosexual transmission; viral compartmentalization

PMID:
30996101
PMCID:
PMC6580966
[Available on 2019-12-14]
DOI:
10.1128/JVI.01769-18

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