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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. pgupta1+@pitt.edu
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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    • "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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    • "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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