Preferential replication of FIV in activated CD4(+)CD25(+)T cells independent of cellular proliferation.
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.
Joshi
Anjali
A
Immunology Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Vahlenkamp
Thomas W
TW
Garg
Himanshu
H
Tompkins
Wayne A F
WA
Tompkins
Mary B
MB
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002415:Cats; D002455:Cell Division / Q000276:immunology; D004195:Disease Models, Animal; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D016089:Immunodeficiency Virus, Feline / Q000502:physiology*; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000032:analysis; D017735:Virus Latency; D014779:Virus Replication
D015375:Receptors, Interleukin-2