Arch Virol (1999) 144: 1043–1055
Replication-incompetent Sendai virus can suppress
the antiviral action of type I interferon
, B. Gotoh
, T. Komatsu
, K. Takeuchi
, and T. Miyadai
Central Research Laboratories, Fukui Medical University, Matsuoka, Fukui, Japan
Department of Microbiology, Fukui Medical University, Matsuoka, Fukui, Japan
Accepted February 22, 1999
Summary. Altered baby hamster kidney (BHK-R) cells, which were established
by serial passage of BHK cells in the presence of Sendai virus (SeV), allowed
vesicular stomatitis virus (VSV) to replicate despite treatment with type I inter-
feron (IFN). We have analyzed here mechanisms of the unresponsiveness to IFN.
BHK-R cells cultured in the absence of SeV for 10 days under the conditions of
no cell division (BHK-R10D) became sensitive to IFN. Studies on induction of
unresponsiveness to IFN in BHK-R10D cells revealed that entry of SeV nucleo-
capsids into a cell was essential. Interestingly, even UV-inactivated SeV but not
Newcastle disease virus was found to be able to confer resistance to IFN on HeLa
or BHK cells as well as on BHK-R10D cells, suggesting that the IFN-resistance
resulted from functions of SeV independent of replication of the viral genome
but not from mutations of the cellular genome. Furthermore immunoﬂuorescent
experiments demonstrated that UV-inactivated SeV could rescue VSV replication
from the antiviral action of IFN without expression of SeV antigens, conﬁrming
that the secondary transcription resulting in synthesis of large amounts of viral
proteins was dispensable for the IFN-resistance. Thus we have revealed a unique
strategy of SeV against the antiviral action of IFN.
Isolation of mutant cell lines unresponsive to interferon (IFN) has made a great
contribution to identiﬁcation of molecules responsible for the signaling pathway
for IFN [3, 26, 27]. Genes involved in the signaling pathway have been cloned
by genetic complementation for the recessive phenotypes of mutants.
Present address: Department of Marine Bioscience, Fukui Prefectural University,
Obama, Fukui, Japan.