These cell lines and matched wild type littermate cells were infected with the gammaretrovirus Moloney MLV and the lentiviruses HIV and FIV. Only the lentiviruses showed reduced infection efficiency in the BER deletion cells. Quantitation of the HIV provirus shows that integration to the host genome is reduced in the absence of BER proteins. PICs derived from BER deficient cells showed reduced integration activity compared to PICs from wild type cells. PIC integration activity from Pol?deficient cells was rescued with the addition of recombinant POL?protein. Oxidative damage associated BER proteins appear to affect lentiviral infection efficiency at the integration step. To determine any effect of BER proteins on reverse transcription efficiency, we evaluated the accumulation of HIV cDNA over time. The BER WT and null cell lines were infected with an HIV vector, DNA fractions were collected at multiple time points, and analyzed by quantitative PCR for late reverse transcripts. The late reverse transcript primer set spans the reverse transcription primer binding site and amplifies all cDNA forms including complete linear cDNA, 1LTR and 2LTR circles, and integrated provirus. A previous report suggested that the BER protein Ape1, as part of the cytoplasmic SET complex, protects HIV from autointegration. Ape1 also plays an essential role in BER in the nucleus and a likely role in the mitochondria. To determine if the BER DNA glycosylases might also act by preventing HIV autointegration, DNA was analyzed by qPCR for autointegration BMS-764459 products at 24 hpi. There was no difference in HIV autointegration products between wild type and BER DNA glycosylase deletion cells. Retroviral 2LTR circles are only found in the nuclear compartment and are an indicator of successful nuclear import of the retroviral PIC. DNA from infected cells at 24 hpi was analyzed for 2LTR circles by qPCR. There was no significant difference in the accumulation of 2LTR circles between wild type and BER deletion cells, indicating that the BER proteins do not affect nuclear import of HIV cDNA. The integrated HIV provirus was also measured by qPCR in BER cell lines. DNA at 72 hpi was amplified by primers to HIV and host Alu elements and BML-210 further measured by qPCR. While there appears to be no difference in reverse transcription, autointegration, or nuclear import of HIV cDNA, the BER mutant cell lines show reduced integrated provirus compared to wild type cells. During the process of retroviral integration, the viral cDNA is covalently joined to the host chromosome but is flanked by 4�C6 base pair gaps of host DNA and a 59 dinucleotide flap of viral DNA.