Human immunodeficiency virus type 1 shedding pattern in semen correlates with the compartmentalization of viral Quasi species between blood and semen

Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
The Journal of Infectious Diseases (Impact Factor: 5.78). 08/2000; 182(1):79-87. DOI: 10.1086/315644
Source: PubMed

ABSTRACT High levels of human immunodeficiency virus (HIV) type 1 have been detected in semen at all stages of disease. However, it is not clear whether HIV-1 is shed in semen continuously or intermittently. In a prospective longitudinal study, viral RNA was measured weekly for 10 weeks in semen and blood of HIV-seropositive subjects. Results showed three different patterns of HIV-1 shedding in semen: none (28%), continuous (28%), and intermittent (44%). In contrast, there was no change in blood plasma virus load during the study period. Phylogenetic analysis of the envelope sequences of HIV-1 RNA in semen and blood revealed distinct virus populations in semen and blood of intermittent shedders but similar virus populations in the semen and blood of continuous shedder. These results indicate for the first time that HIV-1 is shed primarily in an intermittent manner and that shedding patterns of HIV-1 in semen are related to compartmentalization of HIV-1 between semen and blood.

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    • "Following the entry in to the host cells, HIV undergoes extensive diversification during the natural course of infection due to poor proof reading activity of its reverse transcriptase enzyme. This results in the presence of distinct variants in different tissues and secretions including the lymph node, spleen, brain, lung, and semen [Connor and Ho, 1994; Dittmar et al., 1997; Gupta et al., 2000]. These variants may influence the affinity for host cells and also the biological phenotype "
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    ABSTRACT: The presence of distinct viral variants in different cells and secretions of the same person influences the transmission of HIV as well as the response to the host defense and to therapy. Sperm-associated virus is also a risk factor for sexual transmission of HIV. Characterization of the C2-V3 region of HIV1C env gene by the Heteroduplex Mobility Assay (HMA) and sequencing demonstrated the presence of distinct variants in the peripheral blood mononuclear cells (PBMCs) and the sperm of the same individual (n = 6). The translated amino acid sequences of HIV variants in the PBMCs of all the study participants (n = 12) and spermatozoa of the six participants characterized showed the presence of distinct variants with different numbers of N-linked glycosylation (NLG) sites. Infectivity of PBMCs of these persons by co-culture with PBMCs from healthy individuals as detected by the p24 levels in the culture supernatant did not show a correlation with the blood plasma viral load. Interestingly, the infectivity of the sperm samples from four of the five individuals showed positive correlation with the viral load in seminal plasma. The study suggests the presence of distinct viral variants in the sperm and PBMCs of the same person with differential infectivity, and the NLG sites may be associated with the affinity of HIV to receptor/co-receptor usages as well as affinity toward neutralizing antibodies which may influence the risk of sperm associated virus in sexual transmission of HIV and transmit the virus further to distal cells.
    Journal of Medical Virology 05/2011; 83(5):760-7. DOI:10.1002/jmv.22041 · 2.22 Impact Factor
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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.
    International Journal of Andrology 07/2009; 33(1):e98-108. DOI:10.1111/j.1365-2605.2009.00973.x · 3.21 Impact Factor
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    • "In each chronically infected individual, HIV exists as quasispecies of related genetic variants and anatomic compartmentalization of these variants has been described for blood, the central nervous system, the genital tract, rectal mucosa, lung and saliva (Di Stefano et al., 2001; Gunthard et al., 2001; Gupta et al., 2000; Kemal et al., 2003; Kiessling, 1992; Liuzzi et al., 1996; Paranjpe et al., 2002; Singh et al., 1999; Zhang et al., 2002). 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). "
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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.
    Virology 03/2009; 386(2):373-9. DOI:10.1016/j.virol.2009.01.028 · 3.28 Impact Factor
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