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National Institute of Environmental Health Sciences

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Publication Detail

Title: Stabilized human TRIM5α protects human T cells from HIV-1 infection.

Authors: Richardson, Max W; Guo, Lili; Xin, Frances; Yang, Xiaolu; Riley, James L

Published In Mol Ther, (2014 Jun)

Abstract: Rhesus (rh) but not human (hu) TRIM5α potently restricts human immunodeficiency virus (HIV)-1 infection. It is not clear why huTRIM5α fails to effectively block HIV infection, but it is thought to have a lower affinity for the viral core. Using primary human CD4 T cells, we investigated the ability of huTRIM5α, rhTRIM5α, and the huTRIM5αR323-332 B30.2/SPRY patch-mutant to form cytoplasmic bodies, postulated as key components of the HIV-1 restriction apparatus. Both rhTRIM5α and huTRIM5αR323-332 formed pronounced cytoplasmic bodies, whereas cytoplasmic bodies in T cells overexpressing huTRIM5α were present but more difficult to detect. As expression of all three TRIM5α orthologs was similar at the RNA level, we next investigated the role of protein stability in conferring TRIM5α-mediated HIV-1 restriction. Both steady-state and pulse-chase experiments revealed that the huTRIM5α protein was much less stable than rhTRIM5α, and this difference correlated with higher self-ubiquitination activity. Using a stabilized form of huTRIM5α in which the steady-state expression level was more similar to rhTRIM5α, we observed comparable HIV-1 restriction activity in multi-round HIV-1 challenge assays. Lastly, primary human CD4 T cells expressing a stabilized huTRIM5α were protected from HIV-1-mediated destruction in vivo, indicating that efforts to stabilize huTRIM5α should have significant long-term therapeutic value.

PubMed ID: 24662946 Exiting the NIEHS site

MeSH Terms: Animals; CD4-Positive T-Lymphocytes/metabolism*; CD4-Positive T-Lymphocytes/transplantation; CD4-Positive T-Lymphocytes/virology; Carrier Proteins/genetics*; Carrier Proteins/metabolism*; Cells, Cultured; Cytoplasm/metabolism; Disease Models, Animal; HIV Infections/metabolism; HIV Infections/prevention & control*; HIV-1/growth & development; HIV-1/immunology*; Humans; Macaca mulatta; Mice; Protein Stability; Proteins/genetics*; Proteins/metabolism*; RNA/metabolism; Ubiquitin-Protein Ligases; Ubiquitination

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