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The control of viral infection by tripartite motif proteins and cyclophilin A

Towers, GJ; (2007) The control of viral infection by tripartite motif proteins and cyclophilin A. [Review]. Retrovirology , 4 , Article 40. 10.1186/1742-4690-4-40. Green open access

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Abstract

The control of retroviral infection by antiviral factors referred to as restriction factors has become an exciting area in infectious disease research. TRIM5 alpha has emerged as an important restriction factor impacting on retroviral replication including HIV- 1 replication in primates. TRIM5a has a tripartite motif comprising RING, B- Box and coiled coil domains. The antiviral a splice variant additionally encodes a B30.2 domain which is recruited to incoming viral cores and determines antiviral specificity. TRIM5 is ubiquitinylated and rapidly turned over by the proteasome in a RING dependent way. Protecting restricted virus from degradation, by inhibiting the proteasome, rescues DNA synthesis, but not infectivity, indicating that restriction of infectivity by TRIM5a does not depend on the proteasome but the early block to DNA synthesis is likely to be mediated by rapid degradation of the restricted cores. The peptidyl prolyl isomerase enzyme cyclophilin A isomerises a peptide bond on the surface of the HIV- 1 capsid and impacts on sensitivity to restriction by TRIM5a from Old World monkeys. This suggests that TRIM5a from Old World monkeys might have a preference for a particular capsid isomer and suggests a role for cyclophilin A in innate immunity in general. Whether there are more human antiviral TRIMs remains uncertain although the evidence for TRIM19' s ( PML) antiviral properties continues to grow. A TRIM5- like molecule with broad antiviral activity in cattle suggests that TRIM mediated innate immunity might be common in mammals. Certainly the continued study of restriction of viral infectivity by antiviral host factors will remain of interest to a broad audience and impact on a variety of areas including development of animal models for infection, development of viral vectors for gene therapy and the search for novel antiviral drug targets.

Type: Article
Title: The control of viral infection by tripartite motif proteins and cyclophilin A
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1742-4690-4-40
Publisher version: http://dx.doi.org/10.1186/1742-4690-4-40
Language: English
Additional information: © 2007 Towers; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Immunodeficiency-virus type-1, murine leukemia-virus, restriction factor trim5-alpha, old-world monkey, zinc-binding domain, cd4(+) t-cells, retroviral restriction, simian immunodeficiency, hiv-1 infection, reverse transcription
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/140734
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