Elsevier

Virology

Volume 222, Issue 2, 15 August 1996, Pages 391-400
Virology

Regular Article
The Mutation Rate of Human Immunodeficiency Virus Type 1 Is Influenced by thevprGene

https://doi.org/10.1006/viro.1996.0436Get rights and content
Under an Elsevier user license
open archive

Abstract

A system has been designed to study thein vivoforward rate of mutation of human immunodeficiency virus type 1 (HIV-1) during one round of replication. A HIV-1 shuttle vector was used that contained thelacZα peptide gene as a reporter for mutations. The forward mutation rate of HIV-1 was found to be 3 × 10−5mutations per target base pair per cycle, or about 20-fold lower than the error rates reported for purified HIV-1 reverse transcriptase with sense-strand RNA and DNA templates of thelacZα peptide gene in a cell-free system. To test the hypothesis that thevprgene product might, at least in part, account for the lower mutation rate observedin vivo,a HIV-1 vector was replicated to determine if the mutation rate was higher in the absence of the wild-typevprgene product. Avprshuttle vector had an overall mutation rate as much as 4-fold higher than that of the parental vector. A shuttle vector with an amino acid substitution in Vpr that prevents efficient incorporation of Vpr into virus particles was found to have a mutation frequency similar to that of thevprvector, and was interpreted to indicate a requirement for Vpr incorporation into the virus particle in order to observe the influence ofvpron the mutation rate. Replication of avprshuttle vector in the presence of a wild-typevprexpression plasmid led to a mutation frequency similar to that of the parental vector, suggesting that thevprmutation could be complementedin trans.Immunoprecipitation analysis indicated that Vpr virion incorporation coincided with the influence ofvpron the mutation rate.

Cited by (0)

This paper is dedicated to the memory of Howard M. Temin.

2

Fax: (608) 262-2824; E-mail: [email protected].