Department of Microbiology & Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, 27834, USA.
Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, SK-842 15, Bratislava, Slovak Republic.
Sci Rep. 2018 Sep 20;8(1):14105. doi: 10.1038/s41598-018-32350-0.
The oncogenic gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV), are etiologically associated with a variety of human cancers, including Burkitt's lymphoma (BL), Hodgkin lymphoma (HL), Kaposi's sarcoma (KS), and primary effusion lymphoma (PEL). Recently, we demonstrated KSHV infection of B- and endothelial cells to significantly upregulate the expression of interferon induced transmembrane protein 1 (IFITM1) which in turn enhances virus entry. This is an extension of the above study. In here, we determined EBV infection of cells to trigger IFITM1 expression, in vitro. Silencing IFITM1 expression using siRNA specifically lowered gammaherpesvirus infection of cells at a post binding stage of entry. A natural model system to explore the effect of IFITM1 on gammaherpesvirus infection in vivo is infection of BALB/c mice with murine gammaherpesvirus 68 (MHV-68). Priming mice with siRNA specific to IFITM1 significantly lowered MHV-68 titers in the lung specimens compared to priming with (NS)siRNA or PBS. MHV-68 titers were monitored by plaque assay and qPCR. Taken together, for the first time, this study provides insight into the critical role of IFITM1 to promoting in vivo gammaherpesvirus infections.
致癌的γ疱疹病毒，如 EBV（Epstein-Barr 病毒）和 KSHV（卡波西肉瘤疱疹病毒），与多种人类癌症的病因有关，包括 Burkitt 淋巴瘤（BL）、霍奇金淋巴瘤（HL）、卡波西肉瘤（KS）和原发性渗出性淋巴瘤（PEL）。最近，我们发现 KSHV 感染 B 细胞和内皮细胞可显著上调干扰素诱导跨膜蛋白 1（IFITM1）的表达，进而增强病毒进入。这是上述研究的延伸。在这里，我们确定了 EBV 感染细胞会触发 IFITM1 的表达，这是在体外进行的。使用 siRNA 沉默 IFITM1 的表达会特异性降低细胞中 γ疱疹病毒的感染，在病毒进入的结合后阶段。体内研究 IFITM1 对 γ疱疹病毒感染影响的天然模型系统是用鼠 γ疱疹病毒 68（MHV-68）感染 BALB/c 小鼠。用针对 IFITM1 的 siRNA 对小鼠进行预刺激，与用（NS）siRNA 或 PBS 预刺激相比，可显著降低肺组织中的 MHV-68 滴度。通过噬菌斑测定和 qPCR 监测 MHV-68 的滴度。综上所述，本研究首次提供了 IFITM1 促进体内 γ疱疹病毒感染的关键作用的见解。
