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: 6). 08/2000; 182(1):79-87. DOI: 10.1086/315644
Source: PubMed


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 · 2.35 Impact Factor
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    • "Previous studies have already shown that intermittent HIV RNA shedding can occur in semen from treated patients with undetectable HIV viral load in blood [9], [13], [17]. Our results confirm those of Marcelin et al. on 257-paired blood and semen samples followed for greater than 6 months [12]. "
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    ABSTRACT: The risk of male-to-female intravaginal HIV-1 transmission is estimated at about 1 event per 200-2000 coital acts. The aim of this study was to assess the residual risk of HIV presence in semen in patients under HAART therapy. The study took place in France from October 2001 to March 2009. 394 paired blood and semen samples were provided from 332 HIV-1 infected men. The Roche Cobas AMPLICOR Monitor HIV assay was used to quantify HIV-1 RNA in blood and in seminal plasma. Three percent of 394 HIV-1 infected men enrolled in an assisted reproductive technology program harbored detectable HIV-1 RNA in semen, although they had no other sexually transmitted disease and their blood viral load was undetectable for at least 6 months under antiretroviral treatment. These data suggest that undetectable plasma HIV RNA means a lower risk of viral transmission through seminal fluid on a population level, but not necessarily at the level of the individual.
    PLoS ONE 05/2010; 5(5):e10569. DOI:10.1371/journal.pone.0010569 · 3.23 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.
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