Poly(ADP-ribose) polymerase 1 is not strictly required for infection of murine cells by retroviruses.
The DNA-breaking and -joining steps initiating retroviral integration are well understood, but the later steps, thought to be carried out by cellular DNA repair enzymes, have not been fully characterized. Poly(ADP-ribose) polymerase 1 (PARP-1) has been proposed to play a role late during retroviral integration, because infection by human immunodeficiency virus (HIV)-based vectors was reported to be strongly inhibited in PARP-1-deficient fibroblasts. PARP-1, a nuclear enzyme, binds tightly to nicked DNA and synthesizes poly(ADP-ribose) as an early response to DNA damage. To investigate the role of PARP-1 in retroviral integration, we infected wild-type and PARP-1-deficient mouse embryonic fibroblasts (MEFs) separately with two HIV type 1-derived, vesicular stomatitis virus G-pseudotyped lentivirus vectors. Surprisingly, infection of both wild-type and PARP-1-deficient cells was observed with both vectors. Marker gene transduction and provirus formation by one vector was reduced by 45 to 75% compared to the wild type, but the other vector was unaffected by the PARP-1 mutant. In addition, PARP-1-deficient MEFs infected with Moloney murine leukemia virus showed no decrease in virus output after infection compared to the wild type. We conclude that PARP-1 cannot be strictly required for retroviral infection because replication steps, including integration, can proceed efficiently in its absence.
Siva
Amara C
AC
Infectious Disease Laboratory, The Salk Institute, La Jolla, California 92037, USA.
Bushman
Frederic
F
D000818:Animals; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D051379:Mice; D011065:Poly(ADP-ribose) Polymerases / Q000172:deficiency / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D012192:Retroviridae Infections / Q000209:etiology / Q000378:metabolism / Q000821:virology; D016662:Virus Integration; D014779:Virus Replication
D004279:DNA, Viral; D011065:Poly(ADP-ribose) Polymerases