Low Replication Capacity Virus Is Preferentially Transmitted In Mother-To-Child-Transmission But Not In Adult-To-Adult-Transmission Of HIV-1

Previous studies of the transmitted/founder virus compared to viral quasispecies in the donor have yielded conflicting results. In heterosexual adult-to-adult transmission (ATAT), the viral replicative capacity (VRC) of transmitted virus is reportedly either similar to, or somewhat higher than, that of donor virus, whilst transmitted virus in mother-to-child transmission (MTCT) has a significantly lower VRC than that of maternal virus. These discrepancies may be explained by the different methodologies used in these studies, or they may reflect true differences in the transmission bottleneck. To resolve this question, we here use the same methodology to compare transmitted versus donor virus in MTCT and ATAT. We show that, in a South African mother-child cohort, infant virus samples obtained at 1-2 days after birth had VRC significantly lower than in the mothers (p=0.0003). By contrast, in Zambian ATAT transmission pairs, VRC of transmitted virus was similar to or somewhat higher than donor virus (p=ns). The VRC of virus transmitted to the recipient, compared to that in the donor, was significantly lower in MTCT versus heterosexual ATAT (p=0.01). These studies demonstrate that fundamental differences exist between the viruses transmitted via the MTCT and ATAT bottlenecks that are not explained by methodological factors. This result is of importance since transmission of low replicative capacity virus results in low immune activation and a small viral reservoir, and therefore the preferential transmission of low fitness viruses in MTCT might be expected to increase cure potential in in utero infected infants and children.