Semen-Specific Genetic Characteristics of Human Immunodeficiency Virus Type 1 env

University of California, San Diego, Division of Biological Sciences, 9500 Gilman Dr., MC 0679, La Jolla, CA 92093, USA.
Journal of Virology (Impact Factor: 4.44). 02/2005; 79(3):1734-42. DOI: 10.1128/JVI.79.3.1734-1742.2005
Source: PubMed


Human immunodeficiency virus type 1 (HIV-1) in the male genital tract may comprise virus produced locally in addition to virus
transported from the circulation. Virus produced in the male genital tract may be genetically distinct, due to tissue-specific
cellular characteristics and immunological pressures. HIV-1 env sequences derived from paired blood and semen samples from the Los Alamos HIV Sequence Database were analyzed to ascertain
a male genital tract-specific viral signature. Machine learning algorithms could predict seminal tropism based on env sequences with accuracies exceeding 90%, suggesting that a strong genetic signature does exist for virus replicating in the
male genital tract. Additionally, semen-derived viral populations exhibited constrained diversity (P < 0.05), decreased levels of positive selection (P < 0.025), decreased CXCR4 coreceptor utilization, and altered glycosylation patterns. Our analysis suggests that the male
genital tract represents a distinct selective environment that contributes to the apparent genetic bottlenecks associated
with the sexual transmission of HIV-1.

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Available from: Satish Pillai
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    • "High seminal viral load before treatment initiation is to date the only factor found to correlate with persistent release of HIV in semen despite HAART [3]. Several phylogenetic studies demonstrated that HIV in semen arises from local productive sources within the MGT and/or, depending on the individuals, from passive diffusion from the blood [8], [9], [10] (previous references in [7]). Compartmentalization of seminal strains was also recently shown in macaques [11]. "
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    ABSTRACT: The male genital tract is suspected to constitute a viral sanctuary as persistent HIV shedding is found in the semen of a subset of HIV-infected men receiving effective antiretroviral therapy (HAART). The origin of this persistent shedding is currently unknown. Phylogenetic studies indicated that HIV in semen from untreated men arises from local sources and/or passive diffusion from the blood. We previously demonstrated in human and macaque low levels and localized infection of several semen-producing organs by HIV/SIV. Using a macaque model, this study investigates the impact of short term HAART (2-4 weeks) initiated either during the asymptomatic chronic stage or 4 h post-intravenous inoculation of SIVmac251 on the infection of male genital organs. Short term HAART during the chronic stage decreased blood viral load. No major impact of HAART was observed on SIV DNA levels in male genital organs using a sensitive nested PCR assay. Using in situ hybridization, SIV RNA+ cells were detected in all male genital tract organs from untreated and treated animals with undetectable blood viral load following HAART. Infected CD68+ myeloid cells and CD3+ T lymphocytes were detected pre- and post-HAART. In contrast, short term HAART initiated 4 h post-SIV exposure led to a drastic decrease of the male genital tissues infection, although it failed to prevent systemic infection. In both cases, HAART tended to decrease the number of CD3+ T cells in the male organs. Our results indicate that the established infection of male genital organs is not greatly impacted by short term HAART, whereas the same treatment during pre-acute phase of the infection efficiently impairs viral dissemination to the male genital tract. Further investigations are now needed to determine whether infection of male genital organs is responsible for long term persistent HIV shedding in semen despite HAART.
    Full-text · Article · May 2012 · PLoS ONE
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    • "Of interest is that HIV shedding in semen may be intermittent, a phenomenon yet to be explained and not linked to variations in the blood viral load (Coombs et al., 1998; Gupta et al., 2000; Bujan et al., 2004). As infected leucocytes in semen produce viral strains that are different from those in blood leucocytes (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., 2004a, 2004b; Pillai et al., 2005), this indicates that the infected leucocytes and the free virions contaminating semen have distinct origins within the male genital tract, therefore suggesting that several semen-producing organs are infected and contribute either free virus or infected cells. The potential sources of virus in the MGT are discussed below. "
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    ABSTRACT: Despite semen being the main vector of human immunodeficiency virus (HIV) dissemination worldwide, the origin of the virus in this bodily fluid remains unclear. It was recently shown that several organs of the male genital tract (MGT) are infected by HIV/simian immunodeficiency virus (SIV) and likely to contribute to semen viral load during the primary and chronic stages of the infection. These findings are important in helping answer the following questions: (i) does the MGT constitute a viral reservoir responsible for the persistence of virus release into the semen of a subset of HIV-infected men under antiretroviral therapy, who otherwise show an undetectable blood viral load? (ii) What is the aetiology of the semen abnormalities observed in asymptomatic HIV-infected men? (iii) What is the exact nature of the interactions between the spermatozoa, their testicular progenitors and HIV, an important issue in the context of assisted reproductive techniques proposed for HIV-seropositive (HIV+) men? Answers to these questions are crucial for the design of new therapeutic strategies aimed at eradicating the virus from the genital tract of HIV+ men--thus reducing its sexual transmission--and for improving the care of serodiscordant couples wishing to have children. This review summarizes the most recent literature on HIV infection of the male genital tract, discusses the above issues in light of the latest findings and highlights future directions of research.
    Full-text · Article · Jul 2009 · International Journal of Andrology
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    • "Genetic differences between blood and semen-derived HIV-1 have been widely reported (Byrn and Kiessling, 1998; Delwart et al., 1998; Gupta et al., 2000; Vernazza et al., 1997; Zhu et al., 1996), due at least in part to the fact that male genital tract tissues can serve as distinct sites of replication leading to strains exhibiting specific characteristics (Kiessling et al., 1998; Paranjpe et al., 2002; Ping et al., 2000). Recent studies suggest that the male genital tract represents a selective reservoir that leads to genetic bottlenecks associated with sexual transmission of HIV-1 (Pillai et al., 2005). HIV isolates of mucosal origin, either free virus or cell-associated, are seldom used in in vitro studies of sexual transmission even though they are probably more representative and pertinent than adapted laboratory strains. "
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    ABSTRACT: Genetic differences between blood and mucosal-derived HIV-1 strains have been widely reported. As amplification of HIV-1 strains from mucosal samples including semen or saliva by co-culture has low sensitivity, we developed the construction of chimeric viruses expressing wild-type seminal HIV-1 envelope protein. Chimeric viruses were produced by co-transfection of a V1-V3 deleted pNL 43 vector and PCR fragments spanning the deleted region, amplified from HIV-1 RNA positive seminal plasma samples. After an initial testing of co-receptor usage by a tropism recombinant test, replication capacity and amplification of these recombinant viruses were assessed using PBMC. Four chimeric replicative strains, all using CXCR4 as coreceptor, were produced. The interaction between cell-free viral particles and reporter cell lines was assessed by confocal microscopy. These replicative chimeras exhibiting HIV-1 env from seminal strains represent useful tools for the in vitro study of the heterosexual transmission of HIV-1 and testing of microbicide activity.
    Full-text · Article · Mar 2009 · Virology
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