Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene.

Abstract:

:Little is known about virus-host cell interactions that regulate the lytic potential of viruses during productive replication. Sindbis virus (SV), a single-stranded positive-sense RNA virus in the alphavirus genus (family Togaviridae), results in lytic infection in most vertebrate cell lines, but persistent productive infection in post-mitotic neurons. The cellular oncogene bcl-2, which encodes an inner mitochondrial membrane protein of M(r) 26,000 (ref. 2), blocks programmed cell death (apoptosis) in neurons. We therefore investigated whether SV infection induces programmed cell death in non-neuronal cells, and if so, whether virus-induced programmed cell death can be blocked by transfection with bcl-2. We demonstrate that SV infection of baby hamster kidney (BHK-2), mouse neuroblastoma (N18), and rat prostatic adenocarcinoma (AT-3) cells results in programmed cell death, whereas SV infection of bcl-2-transfected AT-3 cells results in long-term persistent productive infection. Thus cellular bcl-2 oncogene expression plays a role in the establishment of persistent viral infection by blocking virus-induced programmed cell death.

journal_name

Nature

journal_title

Nature

authors

Levine B,Huang Q,Isaacs JT,Reed JC,Griffin DE,Hardwick JM

doi

10.1038/361739a0

subject

Has Abstract

pub_date

1993-02-25 00:00:00

pages

739-42

issue

6414

eissn

0028-0836

issn

1476-4687

journal_volume

361

pub_type

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