TRIM5-alpha
From Biocrawler, the free encyclopedia.
TRIM5α (also written as TRIM5alpha or TRIM5-alpha) is a protein that is found in the cells of many mammals and fends off various retrovirus infections. It protects monkeys from infection with HIV-1, and humans from infection with some other viruses.
If a retrovirus has entered a cell, it needs to shed its capsid in order to reversely transcribe its genes, so that they can be expressed by the host cell. It is believed that TRIM5α, which is present in the cytoplasm, somehow recognizes the capsid and blocks its shedding, thereby stopping the virus in its tracks. It thus represents an intracellular defense completely separate from the rest of the body's immune system.
Old World monkeys cannot be infected with HIV-1, the virus that causes AIDS in humans; they can be infected with SIV however, a related virus that can cause similar symptoms but does not infect humans. In 2004, the reason was discovered by Stremlau et al.: the human version of TRIM5α recognizes the capsid of SIV much better than that of HIV-1; the monkey version of TRIM5α does the opposite. If one interferes with the expression of TRIM5α in rhesus monkeys, then those monkeys can be efficiently infected with HIV-1.
Later that year, a group of articles showed that some other retroviruses are restricted by TRIM5α as well, and that the previously known lentivirus susceptibility factor 1 (LV1) and restriction factor 1 (Ref1), which also prevent retrovirus infection, are actually identical to TRIM5α.
Sayah and Luban found in 2004 that Ref1 (i.e. TRIM5α) fails to protect humans against HIV infection because the virus capsid interacts with an intracellular protein called cyclophilin A.
TRIM5α belongs to the TRIM protein family (TRIM stands for TRIpartite Motif); this family was first identified by Reddy in 1992 as the proteins that contain the three motives of a RING finger zinc binding domain, a B-box zinc binding domain, followed by a coiled-coil region. Human TRIM5α consists of 493 amino acids and is encoded on chromosome 11.
References
- Stremlau et al.: "The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys." Nature 2004 Feb 26; volume 427(6977), pages 848-853, PubMed ID 14985764 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14985764)
- K. Lee and V.N. KewalRamani: "In defense of the cell: TRIM5alpha interception of mammalian retroviruses." Proceedings of the National Academy of Sciences U S A. 2004 Jul, volume 20;101(29), pages 10496-10497, PubMed ID 15252204 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15252204)
- D.M. Sayah and J. Luban: "Selection for loss of Ref1 activity in human cells releases human immunodeficiency virus type 1 from cyclophilin A dependence during infection." Journal of Virology 2004 Nov, volume 78(21), pages 12066-12070, PubMed ID 15479848 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15479848)
External links
- Swiss-Prot entry (http://us.expasy.org/cgi-bin/niceprot.pl?Q6BC81)
- sequence data (http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=protein&val=48994821) from the ENTREZ Protein database
