Influenza A virus derived from persistently virus-infected cells shows attenuated cytotoxicity in cultured cells but virulent pathogenicity in mice

The IVpi-43 strain of influenza A virus, a progeny virus derived from persistently virus-infected Madin–Darby canine kidney (MDCK) cells, showed a more attenuated nature in cytopathology in cultured cells than the parental wild-type influenza virus (IVwt) that was used for establishment of the virus carrier culture. Upon infection of MDCK cells, growth of the IVpi-43 virus was restrained with an impaired synthesis of virus structural proteins in the cells. Apoptosis induced by IVpi-43 virus was confined at a low level. The IVpi-43 virus was able to easily cause persistent infection in fresh MDCK cells. In contrast to the in vitro phenotype, the IVpi-43 virus proved highly virulent in mice, with massive and broadly disseminated virus multiplication in the lungs. It was suggested that impaired activity of the neuraminidase molecule of the IVpi-43 virus was responsible for the delayed and faint appearance of apoptosis in the IVpi-43 virus-infected respiratory cells, which made it possible for the virus to replicate for a longer period and to spread to a broader area of the lungs and that abundant numbers of the virus-infected lung cells were killed within a short period by the subsequently established virus-specific immune responses, leading to unrecoverable serious pneumonia.