Mother-to-Child HIV Transmission Bottleneck Selects for Consensus Virus with Lower Gag-Protease-driven Replication Capacity.

2017 | J Virol

Program(s): Laboratory |

Abstract:

HIV infection is in the large majority of cases established by a single variant and understanding the characteristics of successfully transmitted variants is relevant to prevention strategies. Few studies have investigated the viral determinants of mother-to-child transmission. To determine the impact of Gag-protease driven viral replication capacity on mother-to-child transmission, the replication capacities of 148 recombinant viruses encoding plasma derived Gag-protease from 53 non-transmitter mothers, 48 transmitter mothers and 47 infected infants were assayed in an HIV-1 inducible green fluorescent protein reporter cell line. All study participants were infected with HIV-1 subtype C. There was no significant difference in replication capacity between the non-transmitter (n=53) and transmitter mothers (n=44) (p = 0.48). Infant-derived Gag-protease NL4-3 recombinant viruses (n = 41) were found to have a significantly lower Gag-protease-driven replication capacity than those derived from their mothers (p < 0.0001; paired T test). Higher percent similarity to consensus C Gag, p17, p24 and protease was also found in the infants (n = 28) in comparison to their mothers (p = 0.07, p = 0.002, p = 0.03 and p = 0.02 respectively; paired T test). These data suggest that of the viral quasispecies found in the mother, the HIV mother-to-child transmission bottleneck favours the transmission of consensus-like viruses with lower viral replication capacities.IMPORTANCE Understanding the characteristics of successfully transmitted HIV variants has important implications for preventative interventions. Little is known about the viral determinants of HIV mother-to-child transmission (MTCT). We addressed the role of viral replication capacity driven by Gag - a major structural protein that is a significant determinant of overall viral replicative ability and an important target of the host immune response - on the MTCT bottleneck. This study advances our understanding of the genetic bottleneck in MTCT by revealing that viruses transmitted to infants have a lower replicative ability, as well as a higher similarity to the population consensus (in this case HIV subtype C), than that of their mothers. Furthermore, the observation that "consensus-like" virus sequences correspond to lower in vitro replication ability yet appear to be preferentially transmitted suggest that viral characteristics favouring transmission are decoupled from those that enhance replicative capacity.

Text or Node

Naidoo VL

BC Centre for Excellence in HIV/AIDS

Search form

Mother-to-Child HIV Transmission Bottleneck Selects for Consensus Virus with Lower Gag-Protease-driven Replication Capacity.

Search form