MinnCResT Program, Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455; USA.
Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455; USA.
J Gen Virol. 2014 Apr;95(Pt 4):960-967. doi: 10.1099/vir.0.057653-0. Epub 2013 Dec 6.
Trim 5α was the first member of the tripartite motif (TRIM) family of proteins that was identified to potently restrict human immunodeficiency virus type 1 (HIV-1) replication. The breadth of antiretroviral activity of TRIM family members is an active area of investigation. In this study, we demonstrate that human Trim 37 possesses anti-HIV-1 activity. This antiretroviral activity and the manner in which it was displayed were implicated by (1) decreased viral replication upon Trim 37 transient overexpression in virus-producing cells, (2) correlation of the reduction of viral infectivity with Trim 37 virion incorporation, (3) increased HIV-1 replication during siRNA depletion of Trim 37 expression, and (4) reduction in viral DNA synthesis upon Trim 37 transient overexpression. Our findings provide the first demonstration, to our knowledge, of the potent antiviral activity of human Trim 37, and implicate an antiviral mechanism whereby Trim 37 interferes with viral DNA synthesis.
Trim5α 是三部分基序 (TRIM) 蛋白家族中第一个被鉴定为能够有效抑制人类免疫缺陷病毒 1 型 (HIV-1) 复制的蛋白。TRIM 家族成员的抗病毒活性范围是一个活跃的研究领域。在这项研究中,我们证明人类 Trim37 具有抗 HIV-1 活性。这种抗病毒活性及其表现方式表现在以下几个方面:(1) 在产生病毒的细胞中转染 Trim37 后,病毒复制减少;(2) 病毒感染力的降低与 Trim37 病毒粒子的掺入相关;(3) Trim37 表达的 siRNA 耗竭期间 HIV-1 复制增加;(4) Trim37 瞬时过表达后病毒 DNA 合成减少。我们的发现首次证明了人类 Trim37 的强大抗病毒活性,并暗示了一种抗病毒机制,即 Trim37 干扰病毒 DNA 合成。