Temperature sensitivity of two different steps in the viral life cycle of feline immunodeficiency virus

Feline immunodeficiency virus (FIV) multiplication is totally blocked by incubation of infected cells at 41 degrees. This inhibition does not take place with a thermoresistant strain of FIV, designated m41, indicating the role played by the viral genome in temperature sensitivity. We have investigated the steps in the life cycle of wild-type FIV that are thermosensitive and found that they depend on the host cells infected. In CrFK cells, FIV replication was inhibited after the penetration step at 41 degrees. Synthesis of viral RNA and DNA was barely detectable and no viral antigen appeared in the extracellular medium. Nevertheless, viral multiplication resumed on incubation at 37 degrees, suggesting a state of latency at the elevated temperature. In peripheral blood mononuclear cells (PBMCs), the FIV cycle was inhibited at 41 degrees after the synthesis of viral DNA. Several viral mRNAs failed to appear as fully spliced products and no viral antigen was found in the extracellular medium. As in CrFK cells, viral multiplication occurred in PBMCs after a shift to the permissive temperature. These results suggest that at least two steps in the viral life cycle are sensitive to 41 degrees and that two different viral functions of the thermoresistant mutant m41 are modified to overcome temperature sensitivity.