Temperature-sensitive viral infection: inhibition of hemagglutinating virus of Japan (Sendai virus) infection at 41 degrees

While investigating myoblast fusion using enveloped viruses, we unexpectedly found that the production of hemagglutinating virus of Japan (HVJ; Sendai virus) was suppressed temperature dependently in quail myoblasts transformed with a temperature-sensitive Rous sarcoma virus, which proliferate at 35.5 degrees but differentiate at 41 degrees; viral production was normal at 35.5 degrees but suppressed at 41 degrees irrespective of the species of host cells. The production of some viruses, i.e. measles virus, influenza virus, herpes simplex virus type 1 and poliovirus, was also markedly suppressed at 41 degrees, suggesting that a temperature of 41 degrees affects viral infection generally. To clarify the mechanism of the suppression, the infectious pattern of HVJ was examined both at 37 degrees and at 41 degrees in LLC-MK2 cells. The synthesis of HVJ-specific proteins was inhibited at the transcriptional level at 41 degrees, although viral penetration by envelope fusion was not affected. The transcriptional inhibition was also seen in quail fibroblasts, which do not express a 70-kD heat shock protein (HSP70), suggesting that HSP70 is dispensable for the inhibition of viral gene transcription at 41 degrees. Further, when the infected cells were incubated at 41 degrees after the viral proteins had been synthesized at 37 degrees, viral production was also inhibited. Immunofluorescent staining of the cells exposed to 41 degrees showed that HVJ envelope proteins formed large aggregates on the cell surface, into which both M and NP proteins were assembled. Under the electron microscope, HVJ virions appeared normal even at 41 degrees, but were detected in clusters on the cell surface, unlike at 37 degrees. These observations suggested that the release of HVJ virions from the cell surface was inhibited for some reason at 41 degrees. Consequently, it was indicated that two steps, viral gene transcription and the release of virions, were inhibited at 41 degrees.