Intrinsic DNA synthesis fidelity of xenotropic murine leukemia virus-related virus reverse transcriptase.

The FEBS Journal
Verónica BarrioluengoLuis Menéndez-Arias

Abstract

Although recent reports have provided strong evidence to suggest that xenotropic murine leukemia virus-related virus (XMRV) is unlikely to be the causative agent of prostate cancer and chronic fatigue syndrome, this recombinant retrovirus can nonetheless infect human cells in vitro and induce a chronic infection in macaques. In the present study, we determined the accuracy of DNA synthesis of the reverse transcriptases (RTs) of XMRV and Moloney murine leukemia virus (MoMLV) using a combination of pre-steady-state kinetics of nucleotide incorporation and an M13mp2-based forward mutation assay. The results obtained were compared with those previously reported for the HIV type 1 BH10 strain (HIV-1(BH10)) RT. MoMLV and XMRV RTs were 13.9 and 110 times less efficient [as determined by the catalytic rate constant of the nucleotide incorporation reaction ((pol))/equilibrium constant (K(d))] than the HIV-1(BH10) RT in incorporating correct nucleotides. Misinsertion and mispair extension kinetic studies demonstrated that MoMLV RT was more accurate than the HIV-1(BH10) RT. In comparison with the MoMLV RT, the XMRV RT showed decreased mispair extension fidelity and was less faithful when misincorporating C or A opposite A. However, the XM...Continue Reading

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Citations

Nov 28, 2013·The FEBS Journal·Mar Álvarez, Luis Menéndez-Arias
May 12, 2015·Protein Expression and Purification·Kosaku NishimuraKiyoshi Yasukawa
Jul 28, 2018·PLoS Pathogens·Jayna RaghwaniKatrina A Lythgoe
Jul 13, 2020·Trends in Biotechnology·Samara Martín-AlonsoLuis Menéndez-Arias

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