4.6 Article

Functional Evidence for the Involvement of Microtubules and Dynein Motor Complexes in TRIM5α-Mediated Restriction of Retroviruses

Journal

JOURNAL OF VIROLOGY
Volume 88, Issue 10, Pages 5661-5676

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.03717-13

Keywords

-

Categories

Funding

  1. Canadian Institutes of Health Research [MOP-56974, MOP-110960, MOP-102712]

Ask authors/readers for more resources

The tripartite motif (TRIM) family of proteins includes theTRIM5 alpha antiretroviral restriction factor. TRIM5 alpha from many Old World and some New World monkeys can restrict the human immunodeficiency virus type 1 (HIV-1), while human TRIM5 alpha restricts N-tropic murine leukemia virus (N-MLV). TRIM5 alpha forms highly dynamic cytoplasmic bodies (CBs) that associate with and translocate on microtubules. However, the functional involvement of microtubules or other cytoskeleton-associated factors in the viral restriction process had not been shown. Here, we demonstrate the dependency of TRIM5 alpha-mediated restriction on microtubule-mediated transport. Pharmacological disruption of the microtubule network using nocodazole or disabling it using paclitaxel (originally named taxol) decreased the restriction of N-MLV and HIV-1 by human or simian alleles of TRIM5 alpha, respectively. In addition, pharmacological inhibition of dynein motor complexes using erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and small interfering RNA-mediated depletion of the dynein heavy chain (DHC) similarly decreased TRIM5 alpha-mediated restriction. The loss in restriction resulting from either the disassembly of microtubules or the disruption of dynein motor activity was seen for both endogenous and overexpressed TRIM5 alpha and was not due to differences in protein stability or cell viability. Both nocodazole treatment and DHC depletion interfered with the dynamics of TRIM5 alpha CBs, increasing their size and altering their intracellular localization. In addition, nocodazole, paclitaxel, and DHC depletion were all found to increase the stability of HIV-1 cores in infected cells, providing an alternative explanation for the decreased restriction. In conclusion, association with microtubules and the translocation activity of dynein motor complexes are required to achieve efficient restriction by TRIM5 alpha.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available