title: Retroviral restriction factors TRIM5α: therapeutic strategy to inhibit HIV-1 replication.
abstract: Tripartite motif protein 5-alpha (TRIM5α) is a cytoplasmic protein that efficiently recognizes the incoming capsid (CA) protein of retroviruses and potently inhibits virus infection in a species-specific manner. Through directly recognizing and interacting with HIV CA, TRIM5α is capable of disrupting the ordered process of viral uncoating, eventually interfering with HIV-1 reverse transcription and virus replication. TRIM5α protein contains four domains: RING domain, B-box 2 domain, coiled-coil domain, and B30.2 domain (SPRY) domain. All of the domains are necessary for efficient retrovirus restriction and the B30.2 domain has been shown to be the determinant of the specificity of restriction. Species-specific innate resistance against viral infections offers novel avenues for antiviral therapeutics. Various mutants of TRIM5α have been described which differently affect the HIV-1 reverse transcription process. This makes the establishment of new and improved models for HIV replication and AIDS pathogenesis by monitoring endogenous TRIM5α an attractive approach. TRIM5α-mediated restriction is modulated by the host protein Cyclophilin A (Cyp A) which could effectively interact with the CA of HIV-1. Here we will review the structure and roles of TRIM5α protein, the interaction between Cyp A and TRIM5α, as well as gene therapy strategies associated with TRIM5α to inhibit HIV-1 infection.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 250012, Jinan, Shandong, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Weiying
authors.initials: W
authors.lastname: Ge
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy; D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021984:Cyclophilin A / Q000378:metabolism; D015316:Genetic Therapy; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008253:Macaca mulatta; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication / Q000187:drug effects*; D057646:Virus Uncoating / Q000187:drug effects*
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A