Determining the Relative Transmission Fitness of HIV-1 Subtypes A, B, C, and D
Abstract
There is in vivo evidence that suggests the genetic diversity of HIV-1 subtypes influence heterosexual transmission efficiency. To recapitulate sexual transmission in vitro, blocks of genital tissue were exposed to mixtures of genetically different subtype viruses. Migrating immune cells were collected and co-cultured with a CD4+ T-cell line permissive to HIV infection (PM1) to measure dendritic cell virus transfer; HIV-exposed tissues were cultured separately. Next generation sequencing (NGS) of HIV-1 DNA was used to quantify relative infection rates of the various challenge viruses, and to assess fitness differences in infection of the tissue vs. migratory/T cell co-cultures. Our results suggest a HIV-1 subtype’s ability to replicate in susceptible T cells may be predictive of its ability to replicate in susceptible tissue-resident cell populations. However, this may not reflect the ability of a subtype to be transported out of the tissue for infection elsewhere in the body.