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PMID: 9658088 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Brefeldin A inhibits cell-free, de novo synthesis of poliovirus.

Journal of virology ·Vol. 72 ·No. 8 ·1998-08-00 ·Pages 6456-64

Cuconati A, Molla A, Wimmer E

Abstract

Brefeldin A (BFA), an inhibitor of intracellular vesicle-dependent secretory transport, is a potent inhibitor of poliovirus RNA replication in infected cells. We have determined that the unknown mechanism of BFA inhibition of replication is reproduced in the cell-free poliovirus translation, replication, and encapsidation system. Furthermore, we provide evidence suggesting that the cellular mechanism targeted by BFA, the GTP-dependent synthesis of secretory transport vesicles, may be involved in viral RNA replication in the system via a soluble cellular GTP-binding and -hydrolyzing activity. This activity is related to the ARF (ADP-ribosylation factor) family of GTP-binding proteins. ARFs are required for the formation of several classes of secretory vesicles, and some family members are indirectly inactivated by BFA. Peptides that function as competitive inhibitors of ARF activity in cell-free transport systems also inhibit poliovirus RNA replication, and this inhibitory effect can be countered by the addition of exogenous ARF. We suggest that BFA inhibition of replication is diagnostic of a requirement for ARF activity in the cell-free system.

MeSH Terms
ADP-Ribosylation Factors Animals Anti-Bacterial Agents/pharmacology Antiviral Agents/pharmacology Binding, Competitive Brefeldin A Cell-Free System Cyclopentanes/pharmacology GTP-Binding Proteins/antagonists & inhibitors,metabolism Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology HeLa Cells Humans Macrolides Mice Poliovirus/drug effects,growth & development,metabolism,physiology Virus Replication/drug effects
Chemicals
Anti-Bacterial Agents Antiviral Agents Cyclopentanes Macrolides Brefeldin A Guanosine 5'-O-(3-Thiotriphosphate) GTP-Binding Proteins ADP-Ribosylation Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Cuconati A
Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794, USA.
Molla A
Wimmer E
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.8.6456-6464.1998
Published
1998-08-00
Pages
6456-64
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC109807
Subset
IM
Grants
NIAID NIH HHS · R37 AI015122 · United States
NIAID NIH HHS · 5R37AI15122 · United States
External Links
PubMed source DOI: 10.1128/JVI.72.8.6456-6464.1998 PMC Full Text View journal details
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