A mutant murine leukemia virus with a single missense codon in pol is defective in a function affecting integration Academic Article uri icon

Overview

MeSH Major

  • Defective Viruses
  • Genes, Viral
  • Leukemia Virus, Murine
  • Viral Proteins

abstract

  • We have used site-directed mutagenesis of cloned Moloney murine leukemia virus (MuLV) DNA to define a function encoded in the 3' region of the viral pol gene and required for efficient integration of viral DNA. One mutant, MuLV-SF1, contained a single base substitution (C to T at base 4950) that resulted in an arginine to cysteine change in a region highly conserved among retroviruses. Mutant DNA, introduced into rat cells by cotransfection with a herpes simplex virus thymidine kinase gene (HSV tk), directed production of virus particles with reverse transcriptase activity. Infection of cells with these particles led to synthesis of full-length linear and circular forms of unintegrated viral DNA; however, integrated viral DNA was decreased at least by a factor of 10 when examined by DNA hybridization, and the mutant particles were less efficient then wild-type virus at establishing an infection by a factor of at least 300. Pseudotypes formed with the proteins of MuLV-SF1 and the genome of a replication defective marker MuLV, carrying the HSV tk gene, were less effective by at least a factor of 100 in producing tk+ colonies than pseudotypes formed with proteins encoded by wild-type virus. When the MuLV-SF1 pseudotypes did produce tk+ cells, most of the proviruses were integrated aberrantly. We conclude that the MuLV-SF1 pol gene is defective for a function that is required for normal integrative recombination and dissociable from DNA synthesis.

publication date

  • December 1984

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC391944

PubMed ID

  • 6208550

Additional Document Info

start page

  • 6461

end page

  • 5

volume

  • 81

number

  • 20 I