-- Researchers in the United States have shed new light on a poorly understood step in the retroviral integration process.
"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," explained Amara C. Siva and colleagues working at the nonprofit Salk Institute in La Jolla, California.
However, Siva and coauthors found that presence or absence of PARP-1 had little impact on HIV DNA integration or on viral replication.
The researchers compared the course of HIV infection in wild-type and PARP-1-deficient mouse embryonic fibroblasts (MEFs). PARP-1 is a nuclear DNA repair enzyme, widely thought to be involved in the poorly characterized late stages of retroviral integration, they noted.
One of the vesicular stomatitis virus G-pseudotyped lentivirus vectors used in this study was unable to efficiently infect PARP-1-deficient cells, according to the report. However, a similar vector readily infected mutant MEFs despite the absence of PARP-1 expression.
Moreover, Moloney murine leukemia virus replicated with equal efficiency in wild-type and PARP-1-deficient MEFs (Poly(ADP-Ribose) polymerase 1 is not strictly required for infection of murine cells by retroviruses. J Virol 2002 Dec;76(23):11904-10.
Siva and colleagues concluded that "PARP-1 cannot be strictly required for retroviral infection because replication steps, including integration, can proceed efficiently in its absence."
The corresponding author for this report is Frederic Bushman, Infectious Disease Laboratory, The Salk Institute, 10010 N. Torrey Pines Rd., La Jolla, CA 92037, USA. E-mail: firstname.lastname@example.org.
Key points reported in this study include:
Poly(ADP-ribose) polymerase 1 (PARP-1) is not needed for efficient HIV replication
This DNA repair enzyme is thought to play a role in the late stages of viral DNA integration
However, integration and replication were possible in cells lacking PARP-1 expression
This article was prepared by AIDS Weekly editors from staff and other reports.
Siva AC, Bushman F., "Poly(ADP-ribose) polymerase 1 is not strictly required for infection of murine cells by retroviruses", J Virol 2002 Dec;76(23):11904-10.