ABSTRACT
HIV binds specifically to the human mannose receptor (hMR) on vaginal epithelial cells that are devoid of a conventional CD4 receptor. HIV binding to hMR on vaginal epithelial cells induces the production of matrix metalloproteinase 9 (MMP9) leading to degradation of the extracellular matrix, which may increase the risk of HIV entry into vaginal epithelial cells and further transmission into distal cells. Immunofluorescent localization of hMR on vaginal epithelial cells of seronegative females from the general population included the control group (n=52) and seronegative females from serodiscordant couples. There was PCR amplification of DNA from peripheral blood mononuclear cells (PBMCs) of the serodiscordant females for the CCR5 gene flanking the CCR5-Δ32 region; PCR amplification and sequencing of the C2-V3 region of HIV variants in PBMCs and sperm of the infected male partners of the serodiscordant couples; and the presence of hMR on 0-11% of the vaginal epithelial cells of seronegative females (n=39) from serodiscordant couples and 90-95% that of a control group of females (n=52). Nine of these serodiscordant females did not show a CCR5-Δ32 deletion. The translated amino acid sequence of the C2-V3 region of the env gene of HIV-1C in PBMCs (n=9) and sperm (n=5) of the male partners showed the presence of distinct variants and the variation in PBMCs and sperm of serodiscordant males was almost similar to that of infected males from concordant couples. The presence of hMR in a smaller number of vaginal epithelial cells of serodiscordant females prevented binding and HIV entry into these cells and therefore prevented sexual transmission of HIV.
Subject(s)
HIV Infections/transmission , Lectins, C-Type/genetics , Mannose-Binding Lectins/genetics , Receptors, Cell Surface/genetics , Amino Acid Sequence , Base Sequence , Female , Fluorescent Antibody Technique , Genetic Predisposition to Disease/genetics , Genetic Variation , Genotype , HIV Infections/genetics , HIV-1/genetics , Humans , Leukocytes, Mononuclear/metabolism , Male , Mannose Receptor , Polymerase Chain Reaction , Receptors, CCR5/genetics , Sex Factors , Vagina/virologyABSTRACT
The potential risk of HIV-1 infection following human bite although epidemiologically insignificant, but it is biologically possible. There are anecdotal reports of HIV transmission by human bites particularly if saliva is mixed with blood. The oral tissues support HIV replication and may serve as a previously unrecognized HIV reservoir. The HIV infected individuals have more viruses in blood than saliva, possibly due to the potent HIV-inhibitory properties of saliva. The case presented here is of a primary HIV infections following a human bite where in the saliva was not blood stained but it got smeared on a raw nail bed of a recipient. The blood and saliva of the source and blood of the recipient showed a detectable viral load with 91% sequence homology of C2-V3 region of HIV gp120 between the two individuals. The recipient did not receive PEP [post exposure prophylaxis] as his family physician was unaware of salivary transmission. The family physician should have taken PEP decision after proper evaluation of the severe and bleeding bite. Hence it is necessary to treat the HIV infected human bites with post exposure prophylaxis.
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.
