Elsevier

Current Opinion in Virology

Volume 3, Issue 6, December 2013, Pages 692-699
Current Opinion in Virology

HIV accessory proteins versus host restriction factors

https://doi.org/10.1016/j.coviro.2013.08.004Get rights and content

Highlights

  • Host restriction factors are part of the innate immune system.

  • HIV encodes accessory proteins to control host restriction factors.

  • Vif degrades APOBEC3G and inhibits its encapsidation into virions.

  • Vpu degrades CD4 and downmodulates BST-2.

  • Vpx degrades SAMHD1.

Primate immunodeficiency viruses, including HIV-1, are characterized by the presence of accessory genes such as vif, vpr, vpx, vpu, and nef. Current knowledge indicates that none of the primate lentiviral accessory proteins has enzymatic activity. Instead, these proteins interact with cellular ligands to either act as adapter molecules to redirect the normal function of host factors for virus-specific purposes or to inhibit a normal host function by mediating degradation or causing intracellular mislocalization/sequestration of the factors involved. This review aims at providing an update of our current understanding of how Vif, Vpu, and Vpx control the cellular restriction factors APOBEC3G, BST-2, and SAMHD1, respectively.

Graphical abstract

HIV accessory proteins provide a shield that protects the virus from the activity of host restriction factors such as APOBEC3G, SAMHD1, or BST-2.

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Section snippets

Overview

Since its identification as the causative agent of AIDS, HIV-1 has been made responsible for the deaths of millions of people worldwide. And there is no light at the end of the tunnel just yet. One might think that viruses should not have an inherent interest in killing their hosts; after all, why bite the hand that feeds you? In fact, many viruses have adapted to their hosts in a manner that allows a relatively peaceful coexistence. In addition, many viral infections are effectively controlled

Vif

Vif (Viral infectivity factor) is critical for the production of infectious virus in vivo. While vif-deficient viruses can replicate unimpaired in many tissue culture systems, there are no known replication competent vif defective primary HIV or SIV isolates [9••]. Vif targets APOBEC3G, a cellular cytidine deaminase that in the absence of Vif is packaged into virions and causes severe damage to the viral genome by deaminating cytidine residues during reverse transcription of the viral genome [10

Vpu

Vpu is unique to HIV-1 and its predecessor SIV strains. The initial functional property attributed to Vpu was to facilitate virus release from infected cells [24]. It became apparent early on that this function of Vpu was host cell-dependent, suggesting the involvement of host cell factor(s). However, not until 20 years after the initial discovery of Vpu and its effect on virus release was the involvement of BST-2 unraveled [25, 26]. Before the identification of BST-2, different functional

Vpx

Vpx is an accessory protein unique to HIV-2 and SIV. It is believed to have originated by gene duplication from Vpr [52]. Indeed, Vpr and Vpx proteins share several common features: (i) they are both specifically packaged into viral particles through an interaction with the p6 domain of the viral Gag precursor; and (ii) they both assemble an E3 ubiquitin ligase complex consisting of DCAF1 (previously known as Vpr-binding protein, VprBP), DDB1 (damage-specific DNA binding protein1), Cul4

Conclusion

HIV accessory genes, which were once thought to play minor roles in the virus replication cycle have turned out to be key players in the control of the host's innate and intrinsic immune system. Among those, Vif is probably the most critical accessory protein since there are no primary HIV or SIV isolates that are defective in Vif. Vpu and Vpx, by contrast, appear to have more specialized functions that control the mode of virus transmission or facilitate the infection of non-dividing cells,

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgment

K Strebel is supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (1 Z01 AI000669).

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