Replication capacity of simian immunodeficiency virus in cultured macaque macrophages and dendritic cells is not prerequisite for intravaginal transmission of the virus in macaques

In order to test the hypothesis that macrophages and dendritic cells (DCs) in mucosal tissue play an important role in heterosexual transmission of hu man immunodeficiency virus, the replication capacities of two simian immuno deficiency viruses (SIVs) were examined in cultured macrophages and DCs as well as in cultured PBMCs in vitro. The virus strains were a T cell-tropic SIV, SIVmac239, and a T cell- and macrophage-tropic (dual-tropic) SIV, SIVm ac239/316E, The infectivities of these viruses to cynomolgus macaques by in travaginal inoculation were also compared. Although both virus strains repl icated well in cultured PBMCs, SIVmac239 did not replicate in cultured macr ophages, whereas SIVmac239/316E did. Both strains showed little replication in cultured DCs, but a high virus yield could be obtained when SIVmac239/3 1 6E-infected DCs were cocultured with uninfected PBMCs, A mixture of these SIVs was inoculated intravaginally to three monkeys and the virus strain t hat first appeared through the vaginal mucosa was determined. The virus clo nes detected first in PBMCs, inguinal lymph nodes and vaginal wash cells (V WCs) after the virus inoculation were of SIVmac239 in all cases, except for one clone of SIVmac239/316E in VWCs of one monkey at one time-point. These results show that the infectivity of the virus in intravaginal transmissio n did not depend on the cell tropism in vitro of the virus.