title: Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir.
abstract: HIV-1 possesses a viral protein, integrase (IN), which is necessary for its efficient integration in target cells. However, it has been reported that an IN-defective HIV strain is still capable of integration. Here, we assessed the ability of wild type (WT) HIV-1 to establish infection in the presence of IN inhibitors. We observed a low, yet clear infection of inhibitor-incubated cells infected with WT HIV which was identical to cells infected with IN-deficient HIV, D64A. Furthermore, the IN-independent integration could be enhanced by the pretreatment of cells with DNA-damaging agents suggesting that integration is mediated by a DNA repair system. Moreover, significantly faster viral replication kinetics with augmented viral DNA integration was observed after infection in irradiated cells treated with IN inhibitor compared to nonirradiated cells. Altogether, our results suggest that HIV DNA has integration potential in the presence of an IN inhibitor and may serve as a virus reservoir.
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, 53 Shogoin-kawara-cho, Sakyo-ku, Kyoto 606-8507, Japan. hebina@virus.kyoto-u.ac.jp
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ebina
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanemura
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Kozue
authors.initials: K
authors.lastname: Urata
authors.forename: Naoko
authors.initials: N
authors.lastname: Misawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D018076:DNA, Complementary / Q000235:genetics* / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D057809:HEK293 Cells; D015658:HIV Infections / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics; D016662:Virus Integration / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D014764:Viral Proteins; D019427:HIV Integrase