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Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry
Published on: June 26, 2019
TRIM5alpha association with cytoplasmic bodies is not required for antiretroviral activity
Byeongwoon Song1, Felipe Diaz-Griffero, Do Hyun Park
1Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
The tripartite motif (TRIM) protein, TRIM5alpha, restricts infection by particular retroviruses. Many TRIM proteins form cytoplasmic bodies of unknown function. We investigated the relationship between cytoplasmic body formation and the structure and antiretroviral activity of TRIM5alpha. In addition to diffuse cytoplasmic staining, the TRIM5alpha proteins from several primate species were located in cytoplasmic bodies of different sizes; by contrast, TRIM5alpha from spider monkeys did not form cytoplasmic bodies. Despite these differences, all of the TRIM5alpha proteins exhibited the ability to restrict infection by particular retroviruses. Treatment of cells with geldanamycin, an Hsp90 inhibitor, resulted in disappearance or reduction of the TRIM5alpha-associated cytoplasmic bodies, yet exerted little effect on the restriction of retroviral infection. Studies of green fluorescent protein-TRIM5alpha fusion proteins indicated that no TRIM5alpha domain is specifically required for association with cytoplasmic bodies. Apparently, the formation of cytoplasmic bodies is not required for the antiretroviral activity of TRIM5alpha.
Insights
Tripartite motif (TRIM) protein TRIM5alpha restricts retroviruses. Cytoplasmic body formation by TRIM5alpha is not essential for its antiretroviral activity, even when bodies are disrupted.
Area of Science:
- Virology
- Cell Biology
- Protein Biochemistry
Background:
- The tripartite motif (TRIM) protein TRIM5alpha is known to restrict infection by certain retroviruses.
- Many TRIM proteins form cytoplasmic bodies, but their function remains unclear.
- Understanding TRIM5alpha's structure and antiretroviral activity is crucial.
Purpose of the Study:
- To investigate the relationship between TRIM5alpha's cytoplasmic body formation and its antiretroviral activity.
- To determine if specific TRIM5alpha domains are required for cytoplasmic body association.
- To assess the impact of disrupting cytoplasmic bodies on TRIM5alpha's antiviral function.
Main Methods:
- Comparative analysis of TRIM5alpha localization and antiretroviral activity across primate species.
- Treatment of cells with geldanamycin, an Hsp90 inhibitor, to disrupt cytoplasmic bodies.
- Studies using green fluorescent protein-TRIM5alpha fusion proteins to identify domains involved in body formation.
Main Results:
- TRIM5alpha formed cytoplasmic bodies of varying sizes in most primate species, but not in spider monkeys.
- All tested TRIM5alpha proteins demonstrated antiretroviral activity.
- Geldanamycin treatment reduced or eliminated cytoplasmic bodies with minimal impact on retroviral restriction.
- No specific TRIM5alpha domain was found to be essential for cytoplasmic body association.
Conclusions:
- Cytoplasmic body formation is not a prerequisite for TRIM5alpha's antiretroviral activity.
- The structural organization of TRIM5alpha into cytoplasmic bodies does not directly correlate with its ability to restrict retroviral infection.
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