Chapter category: Viruses
HIV Receptors
HIV and Membrane Receptors
Edited by: Dimiter Dimitrov, Christopher Broder and Garry LynchISBN: 1-57059-464-3
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Chapter authors:
Dimitrov, Dimiter S. , Christopher C. Broder
AIDS is characterized by depletion of CD4 T lymphocytes; in 1984 it was shown that CD4 is the primary receptor for HIV-1.1,2 To characterize the HIV-1 receptor and to ascertain that the CD4 cell tropism is determined at the receptor level, it was demonstrated that (1) only CD4 expressing cells supported HIV-1 replication,3 infection by pseudotypes of vesicular stomatitis virus (VSV), bearing HIV-1 envelope,1 and syncytia formation by HIV-1;1 (2) anti-CD4 monoclonal antibodies blocked HIV-1 infection,2 infection by VSV pseudotypes and syncytia formation by HIV-1;1 the effect was observed only when the CD4 cells but not virus or virus-producing cells were preincubated with the antibodies; (3) infection by HIV- 1 reduced the CD4 expression on the surface of the infected cells;1,2 (4) expression of human CD4, by using a cDNA encoding the CD4 molecule,4 was sufficient to render both lymphoid and nonlymphoid human (but not mouse) cells susceptible to HIV-1 infection;5 (5) HIV-1 binds efficiently and specifically to cells expressing CD4, but not to cells lacking CD4 or those expressing CD8;5 and (6) the CD4 molecule coprecipitates with the HIV-1 SU envelope glycoprotein (gp120) after virus binding to CD4 expressing cells suggesting a direct physical association between these two molecules.5,6 It was later found that other molecules, the most notable of them being the galactosyl ceramide (GalC),7 could also mediate HIV-1 infection, albeit at low efficiency. The significance of infection pathways mediated by molecules other than CD4 for HIV pathogenesis is uncertain and we will consider those molecules as alternative receptors. The recent observation that CXCR4 (which in concert with CD4 is able to support HIV-1 entry (discussed in chapters 7 and 8)), can mediate CD4-independent infections by some isolates of HIV-2 ,8 suggests that CXCR4 can also serve as an alternative receptor (unless another unknown molecule serves as a primary receptor for these HIV-2 isolates) as well as a coreceptor depending on the structure of the HIV envelope glycoprotein. In this chapter we review the structure and function of CD4, as the primary HIV receptor, and its interactions with the HIV envelope glycoprotein, as wells as GalC and other molecules as alternative receptors. Several reviews9-21 describe in greater detail work related to CD4 and other retrovirus receptors, and can provide a source of earlier references.
Additional chapters from this book:
Receptors and Virus Infections
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Many (but not all) viruses have evolved to utilize a variety of cell surface molecules for gaining access into the cellular interior. A striking feature of virus adaptation to hosts under selective ...
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HIV Receptors
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AIDS is characterized by depletion of CD4 T lymphocytes; in 1984 it was shown that CD4 is the primary receptor for HIV-1.1,2 To characterize the HIV-1 receptor and to ascertain that the CD4 cell tro...
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The primary viral determinant which interacts with cellular receptors is the envelope glycoprotein (Env). Enveloped viruses encode one or more types of these integral membrane proteins. HIV is no ex...
HIV
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The acquired immunodeficiency syndrome (AIDS) was first recognized as a separate clinical entity (albeit initially under a different name) in 1981.1 It was characterized by immunologic abnormalities...
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Viruses are intracellular parasites whose nucleic acids are encapsulated in proteins encoded by their genomes and their evolutionary history is largely independent of that of their hosts.1 More than...
