title: HIV genetic variation is directed and restricted by DNA precursor availability.
abstract: The effects of deoxynucleoside triphosphate (dNTP) imbalances on the fidelity of human immunodeficiency virus type 1 (HIV-1) replication were investigated. Using detergent permeabilized virions and biased dNTP concentrations different types of hypermutants were readily produced. However, the mutant spectrum was different from naturally occurring hypermutants demonstrating that the host cell may restrict variation. Using a genetic screen based on the blue/white beta-galactosidase complementation assay, G --> A hypermutants were recovered from HIV-infected thymidine treated U937 cells. Furthermore, hypermutants were recovered from 1 to 2% of resting or activated peripheral blood mononuclear cells indicating that small proportions of primary cells had distorted intracellular [dTTP] and [dCTP]. Such imbalances may underlie a proportion of somatic and germline point mutations and shape to some extent the evolution of mammalian and viral genomes.
authors.affiliation: Unité de Rétrovirologie Moléculaire, Institut Pasteur, Paris, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Vartanian
authors.forename: U
authors.initials: U
authors.lastname: Plikat
authors.forename: M
authors.initials: M
authors.lastname: Henry
authors.forename: R
authors.initials: R
authors.lastname: Mahieux
authors.forename: L
authors.initials: L
authors.lastname: Guillemot
authors.forename: A
authors.initials: A
authors.lastname: Meyerhans
authors.forename: S
authors.initials: S
authors.lastname: Wain-Hobson
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D003854:Deoxyribonucleotides / Q000235:genetics; D014644:Genetic Variation; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D016296:Mutagenesis; D009694:Nucleic Acid Precursors / Q000235:genetics*; D014771:Virion / Q000235:genetics
chemical_list: D003854:Deoxyribonucleotides; D009694:Nucleic Acid Precursors