Preferential replication of FIV in activated CD4 +CD25 +T cells independent of cellular proliferation

Abstract

Studies attempting to identify reservoirs of HIV-1 latency have documented that the virus persists as both a latent and productive infection in subsets of CD4 + cells. Reports regarding establishment of a stable HIV-1 infection in quiescent T cells in vitro, however, are controversial. In the present study, we investigated the susceptibility of naive and activated CD4 + cell subsets (distinguished by differential expression of CD25) to feline immunodeficiency virus (FIV) infection, their ability to replicate the virus, and potentially act as a reservoir for virus persistence in infected animals. While both CD4 +CD25 + and CD4 +CD25 − cells are susceptible to FIV infection in vitro and in vivo, only CD4 +CD25 + cells produce infectious virions when cultured with interleukin-2 (IL-2). Latently infected CD4 +CD25 − cells produce infectious virions following ConcanvalinA (ConA) stimulation, which correlates with upregulated surface expression of CD25. In contrast to CD4 +CD25 − cells, CD4 +CD25 + cells remain unresponsive to mitogen stimulation and are relatively resistant to apoptosis whether or not infected with FIV. The ability of CD4 +CD25 + cells to replicate FIV efficiently in the presence of IL-2 but remain anergic and unresponsive to apoptotic signaling suggests that these cells may provide a reservoir of productive FIV infection. On the contrary, CD4 +CD25 − cells seem to establish as latent viral reservoirs capable of being reactivated after stimulation.