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Inhibitors that target gp120 interactions with coreceptor

  • Julie M. Strizki
  • Donald E. Mosier
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

Until 1996, when HIV-1 infection was discovered to involve chemokine receptors (reviewed in [1, 2]), virus isolates were characterized by biological assays on human cell lines as syncytium inducing (SI) or non-syncytium inducing (NSI) [3]. NSI viruses predominate early after transmission, are capable of growth in primary macrophages (macrophage tropism), and fail to grow in most established human T cell lines. SI viruses, by contrast, are found in only a subset of patients after chronic infection, are usually not macrophage tropic, and infect established T cell lines [4]. NSI viruses were found to use CCR5 as the coreceptor for virus entry into target cells, and SI viruses to use CXCR4 for entry, either alone or, more commonly, in addition to CCR5. Since CCR5 and CXCR4 are differentially expressed on the surface of naïve and memory T cells, dendritic cells, and macrophages, coreceptor preference largely explains cell tropism. The importance of CCR5 in viral transmission and as a target for therapeutic intervention was underscored by the discovery of a 32-base pair deletion in the human CCR5 coding region (Δ32 mutation) which, when homozygous, prevents CCR5 surface expression and HIV-1 infection [5, 6]. Individuals with the CCR5 Δ32/Δ32 genotype appear to suffer no clinically obvious detriment, although recent data suggest that they may be more susceptible to West Nile virus encephalitis [7]. The cell tropism of CCR5-using viruses (R5 isolates) probably helps explain their selective transmission [8], although it is still difficult to understand why R5 isolates predominate after parenteral exposure [9].

Keywords

CCR5 Antagonist CXCR4 Antagonist CCR5 Inhibitor Primary Human Immunodeficiency Virus Type Coreceptor Switching 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag/Switzerland 2007

Authors and Affiliations

  • Julie M. Strizki
    • 1
  • Donald E. Mosier
    • 2
  1. 1.Department of VirologySchering-Plough Research InstituteKenilworthUSA
  2. 2.Department of ImmunologyThe Scripps Research InstituteLa JollaUSA

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