Correction of a Carboxyl Terminal Simian Immunodeficiency Virus Nef Frameshift Mutation Restores Virus Replication in Macaques

Overview

Journal Virology

Specialty Microbiology

Date 2010 Mar 23

PMID 20303562

Authors

Yanfang Zheng

Ilnour Ourmanov

Robert M Goeken

Sonya Whitted

Charles R Brown

Alicia Buckler-White

Ranjini Iyengar

Ronald J Plishka

Vanessa M Hirsch

Affiliations

Soon will be listed here.

Abstract

Previous studies demonstrated that the nef gene is a critical determinant of the pathogenicity of simian immunodeficiency virus (SIV) in macaques. In the present study, we evaluated the effect of a spontaneous frameshift mutation in the C-terminus of the nef gene of the minimally pathogenic SIVsmH4i clone. This clone exhibited a single nucleotide deletion in the nef gene relative to pathogenic SIV clones that resulted in a frameshift and addition of 46 amino acids to the C-terminus of Nef. We generated a corrected version of this clone, SIVsmH4i Nef+ that restored Nef protein expression. Inoculation of macaques with SIVsmH4i resulted in delayed and low levels of peak viremia. This contrasted with improved kinetics and robust peak viremia in macaques inoculated with the corrected version. Despite the restoration of in vivo replication ability, neither clone resulted in memory CD4+ T cell loss or disease in a period of two years.

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