hiv-1 entry, inhibitors, and resistancehiv - 1进入、抑制剂和阻力.pdfVIP

Viruses 2010, 2, 1069-1105; doi:10.3390/v2051069 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review HIV-1 Entry, Inhibitors, and Resistance Michael A. Lobritz, Annette N. Ratcliff and Eric J. Arts * Department of Molecular Biology and Microbiology and Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA; E-Mails: michael.lobritz@ (M.A.L.); anr16@ (A.N.R.) * Author to whom correspondence should be addressed; E-Mail: eja3@; Tel.: +1-216-368-8904; Fax: +1-216-368-2034. Received: 23 February 2010; in revised form: 16 April 2010 / Accepted: 18 April 2010 / Published: 29 April 2010 Abstract: Entry inhibitors represent a new class of antiretroviral agents for the treatment of infection with HIV-1. While resistance to other HIV drug classes has been well described, resistance to this new class is still ill defined despite considerable clinical use. Several potential mechanisms have been proposed: tropism switching (utilization of CXCR4 instead of CCR5 for entry), increased affinity for the coreceptor, increased rate of virus entry into host cells, and utilization of inhibitor-bound receptor for entry. In this review we will address the development of attachment, fusion, and coreceptor entry inhibitors and explore recent studies describing potential mechanisms of resistance. Keywords: HIV-1; envelope; gp120; V3 loop; gp41; CCR5; maraviroc; vicriviroc 1. Overview of HIV-1 Antiretroviral Ther