Oral Presentation 8th Australasian Virology Society Meeting and 11th Annual Meeting of the Australian Centre for Hepatitis & HIV Virology Meeting 2015

Female-to-male sexually transmitted HIV-1 strains are less susceptible to inactivation by vaginal short chain fatty acids compared with matched non-transmitted strains. (#47)

Muriel Aldunate 1 2 , David Tyssen 1 , Cath F Latham 1 , Paul A Ramsland 1 2 3 4 , Eric Hunter 5 6 , Gilda Tachedjian 1 2 3
  1. Burnet Institute, Melbourne, VIC, Australia
  2. Monash University, Melbourne, VIC, Australia
  3. University of Melbourne, Melbourne, VIC, Australia
  4. School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Perth, WA, Australia
  5. Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA, U.S.A
  6. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, U.S.A

The majority of HIV-1 infections result from heterosexual transmission and are established by a single viral variant known as a transmitter/founder (T/F) virus. A major risk factor for HIV infection in women is bacterial vaginosis (BV), an imbalance in vaginal microflora. BV alters the pH (>4.5) and short chain fatty acid (SCFA) profile to predominantly acetic acid (BV) vs lactic acid (non-BV). Interestingly, BV in HIV positive women increases HIV acquisition in their male partners by ~3-fold. It is hypothesized that increased vaginal pH and loss of virucidal lactic acid enable the survival of HIV being shed in the female reproductive tract (FRT), enabling transmission from female-to-male and/or mother-to-child, during vaginal birth.  Here, we investigate the susceptibility of female-to-male transmitted subtype C T/F and non-transmitted donor strains to vaginal SCFAs.

Virucidal activity of physiologically relevant SCFAs, at the same pH and active protonated concentrations, were assessed against subtype B and C strains. These included the T/F strain Z3618M, from the male recipient, and matched non-transmitted donor clones Z3618F_5, Z3618F_6, Z3618F_11 and Z3618F_15, with a range of particle infectivities.

Lactic acid exhibited potent virucidal activity against all HIV-1 strains, relative to BV-associated SCFAs. Representative subtype B T/Fs (RHPA and CH058) and subtype C Z3618M_T/F were less susceptible to inactivation by all vaginal SCFAs, showing a 2-log reduction in infectivity. In contrast, treatment of non-transmitted HIV-1 subtypes B and C resulted in a 4-log reduction in virus infectivity or complete inactivation.

We show that lactic acid, a non-BV SCFA, is a more potent HIV virucide than SCFAs produced during BV, suggesting that BV-associated SCFAs are not as protective for the FRT. The reduced susceptibility of T/F strains to vaginal SCFAs may be a trait that enables the survival of HIV-1 shed into the FRT and increases transmission probability from female-to-male and/or mother-to-child.