Diaz-Griffero Felipe, Perron Michel, McGee-Estrada Kathleen, Hanna Robert, Maillard Pierre V, Trono Didier, 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. 2008 Sep 1;378(2):233-42. doi: 10.1016/j.virol.2008.05.008. Epub 2008 Jun 30.
Human TRIM5alpha restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5alpha that acquire the ability to inhibit B-MLV infection prior to reverse transcription without losing the ability to restrict N-MLV infection. Remarkably, these mutants gain the ability to decrease the amount of particulate B-MLV capsids in the cytosol of infected cells. In addition, these mutants gain the ability to restrict SIV(mac) and HIV-2 infection. B-MLV and SIV(mac) infections were blocked by the mutant TRIM5alpha proteins prior to reverse transcription. Thus, the range of retroviruses restricted by human TRIM5alpha can be increased by changes in the B30.2/SPRY domain, which also result in the ability to cause premature uncoating of the restricted retroviral capsid.
人类TRIM5α可限制N型嗜性鼠白血病病毒（N-MLV）的感染，但不能限制B型嗜性MLV（B-MLV）的感染。在此，我们研究了人类TRIM5α的B30.2/SPRY结构域突变体，这些突变体在逆转录之前就获得了抑制B-MLV感染的能力，同时又不丧失限制N-MLV感染的能力。值得注意的是，这些突变体获得了减少感染细胞胞质中颗粒状B-MLV衣壳数量的能力。此外，这些突变体还获得了限制SIV（mac）和HIV-2感染的能力。在逆转录之前，突变的TRIM5α蛋白就能阻断B-MLV和SIV（mac）的感染。因此，通过改变B30.2/SPRY结构域，可以扩大人类TRIM5α所限制的逆转录病毒范围，这也导致了其具有使受限制的逆转录病毒衣壳过早脱壳的能力。
