Viral Molecular Machines pp 223-242

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 726)

Molecular Mechanisms of HIV Entry

  • Craig B. Wilen
  • John C. Tilton
  • Robert W. Doms
Chapter

Abstract

Human immunodeficiency virus (HIV) entry is a complex and intricate process that facilitates delivery of the viral genome to the host cell. The only viral surface protein, Envelope (Env), is composed of a trimer of gp120 and gp41 heterodimers. It is essentially a fusion machine cloaked in a shroud of carbohydrate structures and variable loops of amino acids that enable it to evade the humoral immune response. For entry to occur gp120 sequentially engages the host protein CD4 and then one of two chemokine coreceptors, either CCR5 or CXCR4. CD4 binding facilitates exposure and formation of the coreceptor-binding site, and coreceptor binding then triggers the membrane fusion machinery in the gp41 subunit. Our understanding of HIV entry has led to the development of successful small molecule inhibitors for the clinical treatment of HIV infection as well as insights into viral tropism and pathogenesis.

Abbreviations

6HB

Six-helix bundle

AIDS

Acquired immunodeficiency syndrome

CD4bs

CD4-binding site

Cryo-EM

Cryo-electron microscopy

ECL

Extracellular loop

Env

Envelope

ER

Endoplasmic reticulum

HIV

Human immunodeficiency virus

HR-C

C-terminal heptad repeat

HR-N

N-terminal heptad repeat

R5 HIV

CCR5-tropic HIV

R5X4 HIV

Dual-tropic HIV

SIV

Simian immunodeficiency virus

V3

Variable loop 3

X4 HIV

CXCR4-tropic HIV

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Craig B. Wilen
    • 1
  • John C. Tilton
    • 1
  • Robert W. Doms
    • 1
  1. 1.Department of MicrobiologyUniversity of PennsylvaniaPhiladelphiaUSA

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