Genetic interaction of flavivirus nonstructural proteins NS1 and NS4A as a determinant of replicase function.

Abstract:

:Nonstructural protein 1 (NS1) of yellow fever virus (YF) is a glycoprotein localized to extracytoplasmic compartments within infected cells. We have previously shown that NS1 can be supplied in trans and is required for viral RNA replication, a process thought to occur in membrane-bound cytoplasmic complexes. Here we report that the NS1 gene from a related virus, dengue virus (DEN), is unable to function in the process of YF RNA replication. This virus-specific incompatibility leads to a lack of initial minus-strand accumulation, suggesting that DEN NS1 is unable to productively interact with the YF replicase. Based on a YF deletion mutant that requires NS1 in trans, a genetic screen for suppressor mutants was used to select virus variants able to utilize DEN NS1. In three independent selections, a single mutation was mapped to the NS4A gene, which encodes a putative transmembrane replicase component. This mutation, as well as several additional mutations, was engineered into the NS1-deficient genome and confirmed a genetic interaction between NS1 and NS4A. These findings suggest a potential mechanism for integrating NS1 into the cytoplasmic process of RNA replication.

journal_name

J Virol

journal_title

Journal of virology

authors

Lindenbach BD,Rice CM

doi

10.1128/JVI.73.6.4611-4621.1999

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

4611-21

issue

6

eissn

0022-538X

issn

1098-5514

journal_volume

73

pub_type

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