Host DNA repair enzymes have long been assumed to play a role in HIV replication,
and many different DNA repair factors have been associated with HIV. In order to
identify DNA repair pathways required for HIV infection, we conducted a targeted
siRNA screen using 232 siRNA pools for genes associated with DNA repair. Mapping
the genes targeted by effective siRNA pools to well-defined DNA repair pathways
revealed that many of the siRNAs targeting enzymes associated with the short
patch base excision repair (BER) pathway reduced HIV infection. For six siRNA
pools targeting BER enzymes, the negative effect of mRNA knockdown was rescued
by expression of the corresponding cDNA, validating the importance of the gene
in HIV replication. Additionally, mouse embryo fibroblasts (MEFs) lacking
expression of specific BER enzymes had decreased transduction by HIV-based
retroviral vectors. Examining the role BER enzymes play in HIV infection
suggests a role for the BER pathway in HIV integration.
Publisher: Public Library of Science
Date Published: 23-March-2011
Author(s): Espeseth A., Fishel R., Hazuda D., Huang Q., Xu M., Yoder K., Zhou H.