HIV-1 (co)receptors: implications for vaccine and therapy design.
The ultimate aim of therapy or vaccine design against HIV is to eliminate ongoing virus replication or prevent HIV infection. The task at hand is daunting given the wide array of HIV variants circulating and the immense degree of variation found within the virus, especially in the envelope glycoprotein. HIV utilizes the CD4 receptor and a range of 7 transmembrane chemokine coreceptors for cell entry, specifically CCR5 and CXCR4. These receptors provide a number of targets for therapy design, however, the finding that multiple receptors allow for viral entry suggest that targeting one may cause the virus to swirch to using another receptor. The molecular interactions directing coreceptor usage are complex and can involve the same modifications associated with escape from the effect of neutralizing antibodies (NAbs), indicating that they are not unrelated and can in all liklihood impact on each other. Furthermore, a large array of other receptors, other than CD4, CCR5 and/or CXCR4 can interact with HIV with consequences for HIV tranmssion as well as disease progression.
Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105AZ, Amsterdam, The Netherlands. g.pollakis@amc.uva.nl
Georgios
G
Pollakis
William A
WA
Paxton
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000627:therapeutic use; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D058990:Molecular Targeted Therapy; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015728:Receptors, HIV / Q000037:antagonists & inhibitors* / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
D016915:AIDS Vaccines; D000891:Anti-Infective Agents, Local; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens; C527276:CXCR4 protein, human; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D054299:env Gene Products, Human Immunodeficiency Virus