Uracil-DNA glycosylase-2 (UNG2) is a DNA repair protein that removes uracil from
single and double-stranded DNA through a basic excision repair process. UNG2 is packaged into
new virions by interaction with integrase (IN) and is needed during the early stages of the replication
cycle. UNG2 appears to play both a positive and negative role during HIV-1 replication; UNG2
improves the fidelity of reverse transcription but the nuclear isoform of UNG2 participates in the
degradation of cDNA and the persistence of the cellular genome by repairing its uracil mismatches.
In addition, UNG2 is neutralized by Vpr, which redirects it to the proteasome for degradation, suggesting
that UNG2 may be a new cellular restriction factor. So far, we have not understood why
HIV-1 imports UNG2 via its IN and why it causes degradation of endogenous UNG2 by redirecting
it to the proteasome via Vpr. In this review, we propose to discuss the ambiguous role of UNG2 during
the HIV-1 replication cycle.
Keywords: HIV-1, UNG2, Vpr, replication, BER, UDGs, uracil.
Friedberg EC, Walker GC, Siede W. DNA Repair and Mutagenesis. Washington, DC: ASM Press 1995.
Hrecka K, Hao C, Shun M-C, Kaur S, Swanson SK, Florens L, et al. HIV-1 and HIV-2 exhibit divergent interactions with HLTF and UNG2 DNA repair proteins. Proc Natl Acad Sci USA 2016; 113(27): E3921-30.
Rights & PermissionsPrintExport