Figure 1. Model of the viral genetic-bottleneck following mucosal challenge.

Despite exposing animals mucosally with a large number of genetically distinguishable variants, the systemic dissemination of a single genetic unit can be obtained in NHP models thereby recapitulating HIV-1 infection. Genetic analyses of variants that are transmitted to the inoculum allows for enumerating the number of variants systemically replicating and potentially identifying unique features of these lineages. However, a precise molecular description of how this genetic constraint is accomplished is still largely unknown with the earliest events of viral infection still within a metaphorical black-box. Additional experiments are needed to assess the various contributions of anatomic and other host barriers to infection and current NHP models provide the necessary sensitivity and tissue availability to describe these early events.