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Molecular Mechanisms of HIV Entry

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Viral Molecular Machines

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

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.

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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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  1. Department of Microbiology, University of Pennsylvania, 3610 Hamilton Walk, Johnson Pavilion, Philadelphia, PA, 19104, USA

    Craig B. Wilen, John C. Tilton & Robert W. Doms

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  2. John C. Tilton
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  1. Dept. Biological Sciences, Purdue University, W. State St. 915, West Lafayette, 47907-2054, Indiana, USA

    Michael G. Rossmann

  2. Dept. Biology, Catholic University of America, Washington, 20064, District of Columbia, USA

    Venigalla B. Rao

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Wilen, C.B., Tilton, J.C., Doms, R.W. (2012). Molecular Mechanisms of HIV Entry. In: Rossmann, M., Rao, V. (eds) Viral Molecular Machines. Advances in Experimental Medicine and Biology, vol 726. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0980-9_10

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