Cellular tropism of HIV-1 mediated and contrained by coreceptor dependencies
The ability of cells to migrate to specific sites is critical for the proper functioning of both innate and adaptive immune responses in primates. This selective responsiveness is largely orchestrated by small proteins known as chemokines, which direct immune cells expressing an array of chemokine receptors towards concentrations of intracellular and extracellular pathogens. Given the central role of chemokines and chemokine receptors in mediating immunity as well as homeostasis, it is perhaps not surprising that many pathogens, including HIV type 1 (HIV-1) and simian immunodeficiency virus (SIV), have targeted various aspects of chemokine biology. HIV-1 appears only able to use the chemokine receptors CCR5 and CXCR4 as coreceptors to CD4 to efficiently bind and infect cells in vivo . Interactions between HIV-1 and humans are thought to have evolved more recently than interactions between SIV and other primate species. Despite the ability of HIV-1 and SIV to readily mutate under immune pressure and the fact that CCR5 has undergone a range of adaptations in some primates that reduce the pathogenicity of HIV-1 infection, these viruses have maintained their dependency on the CCR5 coreceptor. This review discusses these issues of co-adaptation and the potential role and impact of coreceptor antagonists that are currently being developed for clinical use.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||Centre for Clinical Immunology and Biomedical Statistics|
|Copyright:||2005 Remedica Medical Education and Publishing|
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