Persistent Noncytocidal Vesicular Stomatitis Virus Infections Mediated by Defective T Particles that Suppress Virion Transcriptase

Abstract

Infectious B virions of vesicular stomatitis virus were 100% lethal to BHK(21) (baby hamster kidney) cells when infecting alone, and persistent noncytocidal infection could not be achieved with cloned B virions alone. However, a mixture of B virions and homologous, short, defective, interfering particles (T particles) of a temperature-sensitive mutant of the virus regularly established persistently infected, noncytocidal carrier cultures. A long T particle was generated during establishment of the carrier culture; we show that this long T particle can establish and maintain persistent noncytocidal infection even when it infects cells along with virulent wild-type B virions. This long T particle causes the production of wild-type B virions with greatly reduced virion transcriptase (EC 2.7.7.6; RNA nucleotidyltransferase) levels when coinfecting the same cells, so it appears to prevent cytopathology by regulating virus transcription. The implications of these findings for rabies and other slowly progressing noncytocidal infections are discussed.