HIV Coreceptors and Their Roles in Leukocyte Trafficking During Neuroinflammatory Diseases

Due to the increasing resistance of HIV-1 to antiretroviral therapies, there has been much emphasis on the discovery and development of alternative therapeutics for HIV-1-infected individuals. The chemokine receptors CXCR4 (Bleul et al. 1996a; Feng et al. 1996; Nagasawa et al. 1996; Oberlin et al. 1996) and CCR5 (Alkhatib et al. 1996; Deng et al. 1996; Dragic et al. 1996) were identified as target molecules from the time their role as coreceptors for HIV-1 entry into leukocytes was first discovered 10 years ago. Initial studies focused on the use of the chemokine ligands, or altered derivatives, of CXCR4 and CCR5 to prevent the entrance of HIV-1 into immune cells (Schols 2006). While these studies showed some initial promise, there was evidence of significant caveats to their use, including selection of alternative coreceptor utilizing strains (Marechal et al. 1999; Mosier et al. 1999) and the potential to cause inflammatory side effects. These data prompted the development and study of small molecule inhibitors of CXCR4 and CCR5, which have also been used to examine the roles of these molecules in a variety of inflammatory and infectious diseases.