HIV transmission

Abstract

HIV-1 is transmitted by sexual contact across mucosal surfaces, by maternal-infant exposure, and by percutaneous inoculation. For reasons that are still incompletely understood, CCR5-tropic viruses (R5 viruses) are preferentially transmitted by all routes. Transmission is followed by an orderly appearance of viral and host markers of infection in the blood plasma. In the acute phase of infection, HIV-1 replicates exponentially and diversifies randomly, allowing for an unambiguous molecular identification of transmitted/founder virus genomes and a precise characterization of the population bottleneck to virus transmission. Sexual transmission of HIV-1 most often results in productive clinical infection arising from a single virus, highlighting the extreme bottleneck and inherent inefficiency in virus transmission. It remains to be determined if HIV-1 transmission is largely a stochastic process whereby any reasonably fit R5 virus can be transmitted or if there are features of transmitted/founder viruses that facilitate their transmission in a biologically meaningful way. Human tissue explant models of HIV-1 infection and animal models of SIV/SHIV/HIV-1 transmission, coupled with new challenge virus strains that more closely reflect transmitted/founder viruses, have the potential to elucidate fundamental mechanisms in HIV-1 transmission relevant to vaccine design and other prevention strategies.

Figure 1.

Laboratory staging and natural history of acute and early HIV-1 infection. The average durations and 95% confidence intervals (parentheses) of the eclipse phase and Fiebig stages (Fiebig et al. 2003) of acute infection are shown in the inset.

Figure 2.

HIV-1 transmission model. HIV-1 virions that breach the mucosa may have different fates. Empirical measurements of virus replication and diversification, together with a mathematical model of random virus evolution, allow for a precise molecular identification of transmitted/founder viruses that are responsible for productive clinical infection (Keele et al. 2008; Lee et al. 2009). R₀ is the reproductive ratio. R₀ > 1 leads to productive clinical infection, whereas R₀ < 1 results in an extinguished infection.

Figure 3.

Model of cervicovaginal infection by HIV-1. Preferential R5 HIV-1 transmission is illustrated along with potential roles for Langerhans cells, dendritic cells, and tissue macrophages. Most HIV-1 transmitted/founder viruses replicate efficiently in CD4⁺ T cells but not in monocyte-derived macrophages (Salazar-Gonzalez et al. 2009; Li et al. 2010), raising questions about the role of macrophages in HIV-1 transmission. Virus-host cell interactions in the initial days of infection have been elucidated primarily in the SIV-Indian rhesus macaque infection model (Haase 2010) and in human tissue explants (Hladik and McElrath 2008). (Adapted from Pope and Haase 2003.)