Masking of the contribution of V protein to sendai virus pathogenesis in an infection model with a highly virulent field isolate

Abstract

Sendai virus V protein is not essential for virus replication in cultured cells but is essential for efficient virus replication and pathogenesis in mice, indicating that the V protein has a luxury function to facilitate virus propagation in mice. This was discovered in the Z strain, an egg-adapted avirulent laboratory strain. In the present study, we reexamined the function of Sendai virus V protein by generating a V-knockout Sendai virus derived from the Hamamatsu strain, a virulent field isolate, which is an appropriate model for studying the natural course of Sendai virus infection in mice. We unexpectedly found that the V-knockout virus propagated efficiently in mice and was as virulent as the wild-type virus. Switching of the functionally important V unique region demonstrated that this region of the Hamamatsu strain was also functional in a Z strain background. It thus appears that the V protein is nonsense in a field isolate of Sendai virus. However, the V protein was required for virus growth and pathogenesis of the Hamamatsu strain in mice when the virulence of the virus was attenuated by introducing mutations that had been found in an egg-adapted, avirulent virus. The V protein therefore seems to be potentially functional in the highly virulent Hamamatsu strain and to be prominent if virus replication is restricted.

Illumination of Parainfluenza Virus Infection and Transmission in Living Animals Reveals a Tissue-Specific Dichotomy

“…While inoculation with only a few PFU of unpassaged Hamamatsu strain SeV results in mortality in mice, the MLD 50 of the virus was attenuated by as much as 400-fold after 50 passages in eggs [80]. When the highly pathogenic Ohita and Hamamatsu strains were adapted to LLC-MK2 cells and chicken eggs, they were found to have selected for mutations in the C protein and untranslated leader region, respectively, which increase replication in cultured cells but attenuate replication and pathogenesis in the lungs of mice [81]–[83]. The bioluminescence imaging system described here would be useful in determining whether the mutations that attenuate replication in the lungs also attenuate replication in the URT and trachea, thereby reducing transmission, or whether they actually promote sustained transmission by supporting nasal and tracheal shedding of virus while reducing pathogenesis in the lungs.…”