Role of Bacterial Vaginosis associated bacterial sialidase in HIV infection
Riley Traviss and Zenda Woodman University of Cape Town, Integrative Biomedical Sciences, Cape Town, South Africa
Studies suggest that women with Bacterial Vaginosis (BV) are at a higher risk of being infected by HIV-1 than those with a microbiome dominated by Lactobacillus spp.. A potential mechanism is the secretion of sialidase by BV-associated bacteria (BVAB) that modify either host cell and/or viral N-glycans, facilitating binding of Envelope (Env) to CD4 and/or CCR5 and thus enhance viral entry. When TZM-bl cells were infected with pseudovirus in the presence of sialidase, infection increased 2-fold and this effect was reduced upon addition of N-Acetyl-2,3-dehydro-2-deoxyneuraminic acid (DMM), an inhibitor of sialidase. Therefore, the addition of bacterial sialidase enhanced HIV infection. When TZM-bl cells were infected with pseudovirus in the presence of brain heart infusion (BHI) medium used to culture the BVAB, Gardnerella vaginalis (GV), abiotic GV culture medium inhibited pseudovirus entry without affecting TZM-bl cell viability. This suggested that either sialidase was not secreted by the GV strain and/or another factor was influencing pseudovirus infection. When the abiotic BHI medium was adjusted to pH 7.48, the inhibitory effect of GV was reduced 2-fold and when the abiotic BHI medium was boiled, GV culture no longer inhibited pseudovirus entry. Therefore, GV secreted a heat labile factor that inhibited pseudovirus infection without being toxic to TZM-bl cells. GV secretes Vaginolysin, a member of the cholesterol-dependent cytolysin family believed to contribute to BV pathogenesis. As the MTT test indicated that TZM-bl cells remained viable during incubation with abiotic GV culture medium, they are unlikely to have lysed. Although we cannot discount the effect of Vaginolysin in our assay, it is possible that anaerobic culture of GV in BHI might stimulate the secretion of a compound that inhibits HIV-1 infection in vivo and that other mitigating factors such as inflammation could negate the protective effect.
Credits: None available.
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