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HIV-1 Coreceptors and Viral Tropism

  • Chapter
Chemokines in Disease

Part of the book series: Contemporary Immunology ((CONTIM))

  • 64 Accesses

Abstract

The past two years have witnessed the rapid merging of the HIV and chemokine-receptor fields, no doubt to the surprise of all involved (reviewed in refs. 1–4). It became evident soon after the discovery of CD4 as the primary receptor for HIV-1 that one or more additional cell-surface molecules (coreceptors) were required in conjunction with CD4 to support entry of the virus into cells (5). The realization that HIV-1 strains exhibit distinct cellular tropisms indicated that strain-specific coreceptors might exist. Over the ensuing decade, numerous candidate coreceptors were proposed, none of which stood the test of time. Finally, the first significant step towards solving this problem came in late 1995 when Cocchi, Lusso, and co-workers identified the CC chemokines RANTES, MIP-1α, and MIP-1β as factors secreted by CD8+ T cells that were able to suppress some HIV-1 strains (6). However, the true significance of this finding was not fully apparent until Berger and colleagues independently identified the first bona fide HIV-1 coreceptor, termed fusin (7). This was an orphan seven transmembrane domain receptor first cloned in 1993 (8). Of significance for understanding HIV-1 tropism was that, whereas fusin was clearly shown to serve as a coreceptor for T-tropic virus strains, expression of fusin with CD4 did not allow entry of the more common M-tropic viruses (7). However, the homology of fusin to the chemokine receptor family indicated that a receptor competent to bind RANTES, MIP1-α, and MIP1-β would be an excellent candidate for the M-tropic virus coreceptor. The publication of a receptor with this binding profile, termed CCR5 (9) enabled five groups to simultaneously identify this molecule as the major HIV-1 coreceptor (10–14). Confirmation that CCR5 is the major HIV-1 coreceptor in vivo came from the finding that individuals who lack CCR5 because of an inherited polymorphism (D32-ccr5) are highly resistant to virus infection, and that individuals who have only one copy of this allele exhibit a delayed progression to AIDS (15–17). Subsequently, fusin was shown to be the receptor for the CXC chemokine SDF-1 and, as a result, was renamed CXCR4 (18,19).

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Authors
  1. Robert W. Doms
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  2. John P. Moore
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  1. Genentech, South San Francisco, CA, USA

    Caroline A. Hébert PhD (Senior Scientist) (Senior Scientist)

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Doms, R.W., Moore, J.P. (1999). HIV-1 Coreceptors and Viral Tropism. In: Hébert, C.A. (eds) Chemokines in Disease. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-706-2_17

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  • DOI: https://doi.org/10.1007/978-1-59259-706-2_17

  • Publisher Name: Humana Press, Totowa, NJ

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