Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission

Abstract

To explore the mechanism of sexual transmission of human immunodeficiency virus type 1 (HIV-1), we compared HIV-1 gp120 sequences in longitudinal samples from five acute seroconvertors with those from their corresponding sexual partners (transmitters). We used a quantitative homoduplex tracking assay to compare the overall genetic composition of HIV-1 quasispecies in each transmission pair and to track the transmitted viruses during the acute and asymptomatic stages of HIV-1 infection. In the chronically infected transmitters, HIV-1 variants in genital secretions differed from those in blood and variants in cells differed from those in cell-free plasma, indicating remarkable sequence heterogeneity in these subjects as well as compartmentalization of the virus in different bodily sites. Conversely, two of five seroconvertors had only a few related variants and three of five harbored only one viral population, indicating that in these subjects the transmitted viruses were typically homogeneous. Transmitted viruses were evident in the donor's seminal plasma (one of five cases) and even more so in their seminal cells (three of five cases), suggesting that both cell-associated and cell-free viruses can be transmitted. In every pair studied, the transmitted variant(s) represents only a minor population in the semen of the corresponding transmitter, thereby providing evidence that HIV-1 selection indeed occurs during sexual transmission.

Full-length complementary DNA of hepatitis C virus genome from an infectious blood sample

“…As in cases of HIV infection, the quasispecies of infectious source of HCV converged to one clone, possibly by selection after transmission. 57 In our study, the same source of HCV that contained infectious virus clones was transmitted to a human and a chimpanzee, and both developed hepatitis. The selection of viral population occurred in both hosts, and the resulting converged clone was different.…”

HIV infection of the male genital tract – consequences for sexual transmission and reproduction

“…It was originally believed that the only source of HIV in semen was infected lymphocytes and macrophages coming from the blood. It has now been shown that the HIV strains present in semen evolve separately from the strains in the blood or in other anatomical compartments (Kroodsma et al, 1994;Vernazza et al, 1994;Zhu et al, 1996;Byrn et al, 1997;Coombs et al, 1998;Eron et al, 1998;Hecht et al, 1998;Kiessling et al, 1998;Eyre et al, 2000;Gupta et al, 2000;Ping et al, 2000;Ghosn et al, 2004b;Pillai et al, 2005). This indicates that the MGT constitutes a viral compartment distinct from the blood and locally produces viral particles that are under a specific selective pressure.…”

Effect of Semen Sampling Frequency on Seminal Antiretroviral Drug Concentration

“…Cell-free HIV may infect CD4 þ cells within the male genital tract, and HIV transmission may be through both cell-free and cellassociated virus. [5][6][7] The fact that each drug in combination antiretroviral therapy may not distribute from the blood into the male genital tract to a similar extent [8][9][10] may result in suboptimally suppressive antiretroviral concentrations with incomplete suppression of seminal HIV and possibly selection of antiretroviral-resistant strains. 11 Thus, the optimal drug combinations for systemic treatment may not be optimal for inhibition of seminal HIV, as the male genital tract may behave as a pharmacological sanctuary.…”