Viruses 2012, 4(2), 309-324; https://doi.org/10.3390/v4020309
Novel Approaches to Inhibit HIV Entry
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
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Received: 16 December 2011 / Revised: 17 January 2012 / Accepted: 7 February 2012 / Published: 21 February 2012
(This article belongs to the Special Issue Virus-Induced Membrane Fusion)
Abstract
Human Immunodeficiency Virus (HIV) entry into target cells is a multi-step process involving binding of the viral glycoprotein, Env, to its receptor CD4 and a coreceptor—either CCR5 or CXCR4. Understanding the means by which HIV enters cells has led to the identification of genetic polymorphisms, such as the 32 base-pair deletion in the ccr5 gene (ccr5∆32) that confers resistance to infection in homozygous individuals, and has also resulted in the development of entry inhibitors—small molecule antagonists that block infection at the entry step. The recent demonstration of long-term control of HIV infection in a leukemic patient following a hematopoietic stem cell transplant using cells from a ccr5∆32 homozygous donor highlights the important role of the HIV entry in maintaining an established infection and has led to a number of attempts to treat HIV infection by genetically modifying the ccr5 gene. In this review, we describe the HIV entry process and provide an overview of the different classes of approved HIV entry inhibitors while highlighting novel genetic strategies aimed at blocking HIV infection at the level of entry. View Full-TextKeywords:
HIV entry; gene therapy; CCR5
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MDPI and ACS Style
Didigu, C.A.; Doms, R.W. Novel Approaches to Inhibit HIV Entry. Viruses 2012, 4, 309-324.