Chapter category: Viruses
The Fusion Cofactors/Coreceptors
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
The principal cell types targeted by HIV-1 in vivo are helper T lymphocytes and cells of the monocyte-macrophage lineage via the CD4 receptor pathway, the primary high affinity receptor for HIV-1.1-3 The HIV-1 envelope glycoprotein serves two functions that are critical in the replication cycle of the virus; binding to CD4 and mediating membrane fusion, as detailed in chapter 4. The high-affinity interaction between envelope glycoprotein and CD4 is the first step in what is most likely a complex set of discrete events that ultimately results in the fusion of the virion and host cell membranes, thus permitting virus entry, for review see references 4-6. HIV-1 Env, as well as the Envs of the related viruses HIV-2 and SIV, mediates a pH-independent fusion event, a common feature of most mammalian retroviruses.7 An analogous mechanism mediates cell-cell fusion between HIV Env-expressing and CD4-expressing cells, resulting in the formation of multinucleated giant cells (syncytia). The ability of syncytia formation has been, and remains, an invaluable assay tool for the study of HIV-1 envelope function although it does have limitations which will be discussed. The post CD4-binding molecular interactions that occur in the envelope-receptor mediated fusion process remain obscure. However, there have been several notable observations that suggest that specific conformational changes occur in the Env-CD4 complex following binding; increased exposure of antibody epitopes on gp120 and gp41,8,9 increased cleavage of the V3 loop by exogenous proteinases,8,10,11 dissociation of gp120 from the surface of virions and Env-expressing cells,12a-16 as well as alterations in CD4 structure as detected by immunological and biochemical techniques.17-19 These observations are discussed in chapter 8.
Additional chapters from this book:
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