mutation rates and intrinsic fidelity of retroviral reverse transcriptases逆转录病毒反转录酶的变异率和内在的忠诚.pdfVIP

Viruses 2009, 1, 1137-1165; doi:10.3390/v1031137 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Mutation Rates and Intrinsic Fidelity of Retroviral Reverse Transcriptases Luis Menéndez-Arias Centro de Biología Molecular “Severo Ochoa” [Consejo Superior de Investigaciones Científicas (CSIC) Universidad Autónoma de Madrid], Campus de Cantoblanco, 28049 Madrid, Spain; E-Mail: lmenendez@cbm.uam.es; Tel.: +34 91 196 4494; Fax: +34 91 196 4420 Received: 20 October 2009; in revised form: 3 December 2009 / Accepted: 3 December 2009 / Published: 4 December 2009 Abstract: Retroviruses are RNA viruses that replicate through a DNA intermediate, in a process catalyzed by the viral reverse transcriptase (RT). Although cellular polymerases and host factors contribute to retroviral mutagenesis, the RT errors play a major role in retroviral mutation. RT mutations that affect the accuracy of the viral polymerase have been identified by in vitro analysis of the fidelity of DNA synthesis, by using enzymological (gel-based) and genetic assays (e.g., M13mp2 lacZ forward mutation assays). For several amino acid substitutions, these observations have been confirmed in cell culture using viral vectors. This review provides an update on studies leading to the identification of the major components of the fidelity center in retroviral RTs. Keywords: reverse transcriptase; fidelity; retroviruses; HIV; DNA po