Instituto de Virología "Dr. JM Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Centro de Investigación en Medicina Traslacional "Severo Amuchástegui" (CIMETSA), Instituto Universitario Ciencias Biomédicas Córdoba (IUCBC), Naciones Unidas 420, Córdoba, Argentina.
Sci Rep. 2022 Aug 25;12(1):14556. doi: 10.1038/s41598-022-18846-w.
Pixuna virus (PIXV) and Río Negro virus (RNV) are mosquito-borne alphaviruses belonging to the Venezuelan Equine Encephalitis (VEE) complex, which includes pathogenic epizootic and enzootic subtypes responsible for life-threatening diseases in equines. Considering that the first steps in viral infection are crucial for the efficient production of new progeny, the aim of this study was to elucidate the early events of the replication cycle of these two viruses. To this end, we used chemical inhibitors and the expression of dominant-negative constructs to study the dependence of clathrin and endosomal pH on PIXV and RNV internalization mechanisms. We demonstrated that both viruses are internalized primarily via clathrin-mediated endocytosis, where the low pH in endosomes is crucial for viral replication. Contributing knowledge regarding the entry route of VEE complex members is important to understand the pathogenesis of these viruses and also to develop new antiviral strategies.
皮昆那病毒（PIXV）和里奥内格罗病毒（RNV）是属于委内瑞拉马脑炎（VEE）病毒复合体的虫媒传播的甲病毒，该病毒复合体包括致病性流行亚型和地方性流行亚型，可导致马属动物罹患危及生命的疾病。鉴于病毒感染的最初步骤对于有效产生新的子代至关重要，本研究旨在阐明这两种病毒复制周期的早期事件。为此，我们使用化学抑制剂和显性负性构建体的表达来研究网格蛋白和内体 pH 值对 PIXV 和 RNV 内化机制的依赖性。我们证明这两种病毒主要通过网格蛋白介导的内吞作用内化，内体中的低 pH 值对于病毒复制至关重要。了解 VEE 病毒复合体成员的进入途径有助于理解这些病毒的发病机制，也有助于开发新的抗病毒策略。
