Ganaie Safder S, Leung Daisy W, Hartman Amy L, Amarasinghe Gaya K
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States; Department of Medicine, Washington University School of Medicine, St Louis, MO, United States.
Adv Virus Res. 2023;117:121-136. doi: 10.1016/bs.aivir.2023.09.001. Epub 2023 Oct 5.
Rift Valley Fever Virus (RVFV) is a negative sense segmented RNA virus that can cause severe hemorrhagic fever. The tri-segmented virus genome encodes for six (6) multifunctional proteins that engage host factors at a variety of different stages in the replication cycle. The S segment encodes nucleoprotein (N) and nonstructural protein S (NSs), the M segment encodes viral glycoproteins Gn and Gc as well as nonstructural protein M (NSm) and the L segment encodes the viral polymerase (L). Viral glycoproteins Gn and Gc are responsible for entry by binding to a number of host factors. Our recent studies identified a scavenger receptor, LDL receptor related protein 1 (Lrp1), as a potential pro-viral host factor for RVFV and related viruses, including Oropouche virus (OROV) infection. Coincidentally, several recent studies identified other LDL family proteins as viral entry factors and receptors for other viral families. Collectively, these observations suggest that highly conserved LDL family proteins may play a significant role in facilitating entry of viruses from several distinct families. Given the significant roles of viral and host factors during infection, characterization of these interactions is critical for therapeutic targeting with neutralizing antibodies and vaccines.
裂谷热病毒(RVFV)是一种负链分节段RNA病毒,可引起严重出血热。这种三分节段的病毒基因组编码六种多功能蛋白,这些蛋白在复制周期的不同阶段与宿主因子相互作用。S节段编码核蛋白(N)和非结构蛋白S(NSs),M节段编码病毒糖蛋白Gn和Gc以及非结构蛋白M(NSm),L节段编码病毒聚合酶(L)。病毒糖蛋白Gn和Gc通过与多种宿主因子结合来负责病毒进入。我们最近的研究确定一种清道夫受体,低密度脂蛋白受体相关蛋白1(Lrp1),是RVFV及相关病毒(包括奥罗普切病毒(OROV)感染)潜在的病毒促进宿主因子。巧合的是,最近的几项研究确定其他低密度脂蛋白家族蛋白作为其他病毒家族的病毒进入因子和受体。总体而言,这些观察结果表明,高度保守的低密度脂蛋白家族蛋白可能在促进几个不同病毒家族的病毒进入方面发挥重要作用。鉴于病毒和宿主因子在感染过程中的重要作用,表征这些相互作用对于用中和抗体和疫苗进行治疗靶向至关重要。