Department of Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL, 32610, USA.
Department of Oral Biology, University of Florida College of Dentistry, 1395 Center Drive, Gainesville, FL, 32610, USA; UF Genetics Institute, Gainesville, FL, 32610, USA; UF Health Cancer Center, Gainesville, FL, 32610, USA; UF Informatics Institute, Gainesville, FL, 32610, USA.
Virology. 2020 Feb;541:160-173. doi: 10.1016/j.virol.2019.12.011. Epub 2019 Dec 30.
Unique among human viruses, Kaposi's sarcoma-associated herpesvirus (KSHV) encodes several homologs of cellular interferon regulatory factors (vIRFs). Since KSHV expresses multiple factors that can inhibit interferon (IFN) signaling to promote virus production, it is still unclear to what extent vIRFs contribute to these specific processes during KSHV infection. To study the function of vIRFs during viral infection, we engineered 3xFLAG-tagged-vIRF and vIRF-knockout recombinant KSHV clones, which were utilized to test vIRF expression, as well as their requirement for viral replication, virus production, and inhibition of the type I IFN pathway in different models of lytic KSHV infection. Our data show that all vIRFs can be expressed as lytic viral proteins, yet were dispensable for KSHV production and inhibition of type I IFN. Nevertheless, as vIRFs were able to suppress IFN-stimulated antiviral genes, vIRFs may still promote the KSHV lytic cycle in the presence of an ongoing antiviral response.
在人类病毒中，卡波西肉瘤相关疱疹病毒（KSHV）编码几种细胞干扰素调节因子（vIRF）的同源物。由于 KSHV 表达多种可抑制干扰素（IFN）信号传导以促进病毒产生的因子，因此尚不清楚 vIRF 在 KSHV 感染期间对这些特定过程的贡献程度。为了研究 vIRF 在病毒感染期间的功能，我们设计了 3xFLAG 标记的 vIRF 和 vIRF 敲除重组 KSHV 克隆，用于检测 vIRF 的表达及其对病毒复制、病毒产生和 I 型 IFN 途径抑制的要求在不同的裂解型 KSHV 感染模型中。我们的数据表明，所有 vIRF 都可以作为裂解病毒蛋白表达，但对 KSHV 的产生和 I 型 IFN 的抑制是可有可无的。然而，由于 vIRF 能够抑制 IFN 刺激的抗病毒基因，因此在持续存在抗病毒反应的情况下，vIRF 仍可能促进 KSHV 的裂解周期。
