title: Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages.
abstract: Human immunodeficiency virus type 1 is able to infect nondividing cells, such as macrophages, and the viral Vpr protein has been shown to participate in this process. Here, we investigated the impact of the recruitment into virus particles of the nuclear form of uracil DNA glycosylase (UNG2), a cellular DNA repair enzyme, on the virus mutation rate and on replication in macrophages. We demonstrate that the interaction of Vpr with UNG2 led to virion incorporation of a catalytically active enzyme that is directly involved with Vpr in modulating the virus mutation rate. The lack of UNG in virions during virus replication in primary monocyte-derived macrophages further exacerbated virus mutant frequencies to an 18-fold increase compared with the 4-fold increase measured in actively dividing cells. Because the presence of UNG is also critical for efficient infection of macrophages, these observations extend the role of Vpr to another early step of the virus life cycle, e.g. viral DNA synthesis, that is essential for replication of human immunodeficiency virus type 1 in nondividing cells.
authors.affiliation: Ohio State University Biochemistry Graduate Program, Columbus, OH 43210, USA.
authors.forename: Renxiang
authors.initials: R
authors.lastname: Chen
authors.forename: Erwann
authors.initials: E
authors.lastname: Le Rouzic
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Kearney
authors.forename: Louis M
authors.initials: LM
authors.lastname: Mansky
authors.forename: Serge
authors.initials: S
authors.lastname: Benichou
mesh_terms: D015153:Blotting, Western; D002384:Catalysis; D002460:Cell Line; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D016334:Genes, vpr; D005982:Glutathione Transferase / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D009000:Monocytes / Q000821:virology; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques; D051981:Uracil-DNA Glycosidase; D014779:Virus Replication
chemical_list: D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D045647:DNA Glycosylases; D051981:Uracil-DNA Glycosidase