the “connection” between hiv drug resistance and rnase h之间的u201c连接u201d艾滋病毒耐药性和核糖核酸酶h.pdfVIP

Viruses 2010, 2, 1476-1503; doi:10.3390/v2071476 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review The “Connection” Between HIV Drug Resistance and RNase H Krista A. Delviks-Frankenberry, Galina N. Nikolenko † and Vinay K. Pathak * Viral Mutation Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA; E-Mails: frankenk@ (K.A.D.-F.); gnikolenko@ (G.N.N.) † Present address: Meso Scale Diagnostics, LLC, Gaithersburg, Maryland 20877, USA. * Author to whom correspondence should be addressed; E-Mail: pathakv@; Tel.: +1-301-846-1710; Fax: +1-301-846-6013. Received: 21 June 2010; in revised form: 20 July 2010 / Accepted: 20 July 2010 / Published: 21 July 2010 Abstract: Currently, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are two classes of antiretroviral agents that are approved for treatment of HIV-1 infection. Since both NRTIs and NNRTIs target the polymerase (pol) domain of reverse transcriptase (RT), most genotypic analysis for drug resistance is limited to the first 300 amino acids of RT. However, recent studies have demonstrated that mutations in the C-terminal domain of RT, specifically the connection subdomain and RNase H domain, can also increase resistance to both NRTIs and NNRTIs. In this review we will present the potential mechanisms by which mutations in