Diaz-Griffero Felipe, Kar Alak, Lee Mark, Stremlau Matthew, Poeschla Eric, Sodroski Joseph
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
Virology. 2007 Dec 20;369(2):400-10. doi: 10.1016/j.virol.2007.08.032. Epub 2007 Oct 24.
The restriction factors, TRIM5alpha in most primates and TRIMCyp in owl monkeys, block infection of various retroviruses soon after virus entry into the host cell. Rhesus monkey TRIM5alpha (TRIM5alpha rh) inhibits human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV) more potently than human TRIM5alpha (TRIM5alpha hu). TRIMCyp restricts infection of HIV-1, simian immunodeficiency virus of African green monkeys (SIV agm) and FIV. Early after infection, TRIMCyp, like TRIM5alpha rh and TRIM5alpha hu, decreased the amount of particulate viral capsid in the cytosol of infected cells. The requirements for the TRIMCyp and TRIM5alpha domains in restricting different retroviruses were investigated. Potent restriction of FIV by TRIMCyp occurred in the complete absence of RING and B-box 2 domains; by contrast, efficient FIV restriction by TRIM5alpha rh required these domains. Variable region 1 of the TRIM5alpha rh B30.2 domain contributed to the potency of HIV-1, FIV and equine infectious anemia virus restriction. Thus, although differences exist in the requirements of TRIMCyp and TRIM5alpha for RING/B-box 2 domains, both restriction factors exhibit mechanistic similarities.
限制因子,大多数灵长类动物中的TRIM5α和夜猴中的TRIMCyp,在病毒进入宿主细胞后不久就能阻断多种逆转录病毒的感染。恒河猴TRIM5α(TRIM5αrh)对人类免疫缺陷病毒(HIV-1)和猫免疫缺陷病毒(FIV)的抑制作用比人类TRIM5α(TRIM5αhu)更强。TRIMCyp可限制HIV-1、非洲绿猴猿猴免疫缺陷病毒(SIVagm)和FIV的感染。感染后早期,TRIMCyp与TRIM5αrh和TRIM5αhu一样,会减少感染细胞胞质溶胶中病毒衣壳颗粒的数量。研究了TRIMCyp和TRIM5α结构域在限制不同逆转录病毒方面的要求。在完全没有RING和B-box 2结构域的情况下,TRIMCyp对FIV有强大的限制作用;相比之下,TRIM5αrh对FIV的有效限制则需要这些结构域。TRIM5αrh B30.2结构域的可变区1对HIV-1、FIV和马传染性贫血病毒的限制作用有影响。因此,尽管TRIMCyp和TRIM5α对RING/B-box 2结构域的要求存在差异,但这两种限制因子在作用机制上具有相似性。