Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir

• Published in: Virology (New York, N.Y.) Vol. 427; no. 1; pp. 44 - 50
• Main Authors: Ebina, Hirotaka, Kanemura, Yuka, Suzuki, Yasutsugu, Urata, Kozue, Misawa, Naoko, Koyanagi, Yoshio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.05.2012
• Subjects: 60 APPLIED LIFE SCIENCES; AIDS VIRUS; DNA; DNA Damage; DNA DAMAGES; DNA REPAIR; DNA, Complementary - genetics; DNA, Complementary - metabolism; DNA, Viral - genetics; GENETIC RADIATION EFFECTS; HEK293 Cells; HIV Infections - virology; HIV Integrase - genetics; HIV Integrase - metabolism; HIV Integrase Inhibitors - pharmacology; HIV reservoir; HIV-1; HIV-1 - enzymology; HIV-1 - genetics; Human immunodeficiency virus 1; Humans; Infection; Infectious Disease; Integrase; Integrase inhibitor; Integration; IRRADIATION; Jurkat Cells; Kinetics; PROTEINS; Provirus; Replication; Viral Load; Viral Proteins - genetics; Virus Integration - genetics; Virus Replication - genetics; HIV-1; Integration; Integrase inhibitor; HIV reservoir; DNA repair; Provirus
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2012.02.004

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.