Mucosal challenge with cell-associated or cell-free feline immunodeficiency virus induces rapid and distinctly different patterns of phenotypic change in the mucosal and systemic immune systems

The majority of human immunodeficiency virus type 1 (HIV-1) infections occur via mucosal transmission through contact with genital secretions containing cell-associated and cell-free virus. However, few studies have assessed whether exposure to cells, HIV-1 infected or uninfected, plays a role in the sexual transmission of HIV-1. This study examined phenotypic changes in mucosal and systemic lymphoid tissue 24 hr after vaginal exposure to in vitro equilibrated infectious doses of cell-associated or cell-free feline immunodeficiency virus, uninfected heterologous cells, or medium alone. We found that even at this early time-point, mucosal exposure to virus induced substantial alterations in the phenotype and distribution of leucocytes, particularly in the tissues of the mucosal immune system. Second, we found that the type of virus inoculum directly influenced the phenotypic changes seen. Vaginal exposure to cell-free virus tended to induce more generalized phenotypic changes, typically in the peripheral immune system (blood and systemic lymph nodes). In contrast, exposure to cell-associated virus was primarily associated with phenotypic shifts in the mucosal immune system (gut and mucosal/draining lymph nodes). In addition, we found that exposure to uninfected heterologous cells also induced alterations in the mucosal immune system. These data suggest that significant immune changes occur within the first 24 hr of virus exposure, well before substantial replication would be anticipated. As the mucosal immune system, and particularly the gut, is an early and persistent target for lentiviral replication, these findings have substantial implications for HIV-1 pathogenesis and vaccine development.