Williams-Wietzikoski CA, Campbell MS, Payant R, Lam A, Zhao H, Huang H, Wald A, Stevens W, Gray G, Farquhar C, Rees H, Celum C, Mullins JI, Lingappa JR, Frenkel LM (2019). Comparisons of human immunodeficiency virus type 1 envelope variants in blood and genital fluids near the time of male-to-female transmission. Journal of virology (ePub ahead of print). (pubmed) (doi)
To better understand the transmission of human immunodeficiency virus type-1 (HIV-1), the genetic characteristics of male blood and genital viruses were compared to 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 genitial specimens 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 twenty-nine 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 despite X4-variants detected within four males. The median genetic distance of the imputed MRCA of the women’s founder viruses was closer to the semen 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 males' blood and genital viruses were consistently 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 have shorter variable loops or fewer N-linked glycosylation sites. The lack of selective factors, except for co-receptor tropism, is consistent with others' findings in male-to-female and high-risk transmissions. The infrequent compartmentization between transmitters' blood and semen viruses suggest that cell-free blood virus likely includes HIV-1 sequences representative of 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 males' genital tract viruses were rarely distinct from blood variants. The imputed founder viruses in women were genetically similar to both 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.