title: Cytoplasmic body component TRIM5{alpha} requires lipid-enriched microdomains for efficient HIV-1 restriction.
abstract: TRIM5α is a member of the tripartite motif (TRIM) family of proteins and affects both early and late phases of the retroviral life cycle. Although TRIM5α multimerizes to form cytoplasmic bodies, which are thought to play an important role in viral restriction, the identity of TRIM5α-containing cytoplasmic bodies remains elusive. To better understand TRIM5α cytoplasmic body constituents and the cellular proteins that could be involved in the TRIM5α-mediated antiviral activities, we sought TRIM5α-binding factors. We identified a lipid microdomain protein flotillin-1/Reggie-2 as an interacting partner of TRIM5α via co-immunoprecipitation. Immunohistochemistry studies confirmed the co-localization of rhesus monkey TRIM5α (TRIM5αrh) cytoplasmic bodies with flotillin-1/Reggie-2. Caveolin-1, another lipid microdomain-associated protein, also co-localized with TRIM5α cytoplasmic bodies. Intriguingly, disruption of cellular cholesterol by cyclodextrin perturbed TRIM5α cytoplasmic body formation. Furthermore, lipid starvation partially relieved the endogenous post-entry restriction of HIV-1 infection, which could be subsequently restored by lipid repletion. These observations indicate the involvement of cellular lipids in TRIM5α-mediated antiviral activities. Given that many viruses utilize cellular lipid microdomains for viral entry and assembly, it is plausible that lipid-enriched domains provide microenvironments where TRIM5α recognizes retroviral components.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Seiga
authors.initials: S
authors.lastname: Ohmine
authors.forename: Ryuta
authors.initials: R
authors.lastname: Sakuma
authors.forename: Toshie
authors.initials: T
authors.lastname: Sakuma
authors.forename: Tayaramma
authors.initials: T
authors.lastname: Thatava
authors.forename: Gonzalo P
authors.initials: GP
authors.lastname: Solis
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003505:Cyclodextrins / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D053586:Virus Internalization
chemical_list: D000090103:Antiviral Restriction Factors; C495540:CAV1 protein, human; D002352:Carrier Proteins; D051242:Caveolin 1; D003505:Cyclodextrins; D008565:Membrane Proteins; D000070584:Tripartite Motif Proteins; C106354:flotillins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases
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