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Review
. 2012 May;2(5):a006940.
doi: 10.1101/cshperspect.a006940.

HIV Restriction Factors and Mechanisms of Evasion

Affiliations
Review

HIV Restriction Factors and Mechanisms of Evasion

Michael H Malim et al. Cold Spring Harb Perspect Med. 2012 May.

Abstract

Retroviruses have long been a fertile model for discovering host-pathogen interactions and their associated biological principles and processes. These advances have not only informed fundamental concepts of viral replication and pathogenesis but have also provided novel insights into host cell biology. This is illustrated by the recent descriptions of host-encoded restriction factors that can serve as effective inhibitors of retroviral replication. Here, we review our understanding of the three restriction factors that have been widely shown to be potent inhibitors of HIV-1: namely, APOBEC3G, TRIM5α, and tetherin. In each case, we discuss how these unrelated proteins were identified, the mechanisms by which they inhibit replication, the means used by HIV-1 to evade their action, and their potential contributions to viral pathogenesis as well as inter- and intraspecies transmission.

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Figures

Figure 1.
Figure 1.
Cell fusion studies can illustrate restriction factor activity.
Figure 2.
Figure 2.
Domain organization of the human APOBEC3G, TRIM5α, and tetherin proteins. Critical domains and motifs are highlighted in color, their functions and attributes are indicated above, and important sequence motifs are shown below. The number of amino acids in each protein is also indicated.
Figure 3.
Figure 3.
Mechanisms of restriction factor function and evasion. HIV-1 RNA is shown in light blue, HIV-1 cDNA in dark blue, and restriction factors in red. The sites of Vif, Vpu, and Nef antagonism are indicated. Refer to text for further details.
Figure 4.
Figure 4.
Components and intermolecular contacts in the cullin5-elonginBC-Vif ubiquitin ligase complex. HIV-1 Vif serves as a receptor protein that interacts with cullin5, elonginB (through a proline-rich motif), elonginC (through a BC box), and A3G. Refer to text for further details.
Figure 5.
Figure 5.
A structural model of how tetherin causes virion retention. In the scenario depicted here, tetherin transmembrane domains infiltrate the virion envelope, whereas the glycophosphatidylinositol anchors remain in the plasma membrane. The tetherin coiled-coil domain thereby physically links cell and virion membranes. Refer to Perez-Caballero et al. (2009) and Fitzpatrick et al. (2010) for alternative models.

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