Orthohantaviruses are zoonotic viruses that are naturally maintained by persistent infection in specific reservoir species. Although these viruses mainly circulate among rodents worldwide, spill-over infection to humans occurs. Orthohantavirus infection in humans can result in two distinct clinical outcomes: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). While both syndromes develop following respiratory transmission and are associated with multi-organ failure and high mortality rates, little is known about the mechanisms that result in these distinct clinical outcomes. Therefore, it is important to identify which cell types and tissues play a role in the differential development of pathogenesis in humans. Here, we review current knowledge on cell tropism and its role in pathogenesis during orthohantavirus infection in humans and reservoir rodents. Orthohantaviruses predominantly infect microvascular endothelial cells (ECs) of a variety of organs (lungs, heart, kidney, liver, and spleen) in humans. However, in this review we demonstrate that other cell types (e.g., macrophages, dendritic cells, and tubular epithelium) are infected as well and may play a role in the early steps in pathogenesis. A key driver for pathogenesis is increased vascular permeability, which can be direct effect of viral infection in ECs or result of an imbalanced immune response in an attempt to clear the virus. Future studies should focus on the role of identifying how infection of organ-specific endothelial cells as well as other cell types contribute to pathogenesis.

直汉坦病毒是人畜共患病毒，通过在特定的水库物种中持续感染而自然保持。尽管这些病毒主要在世界各地的啮齿动物中传播，但仍发生向人的溢出感染。人类中的正汉坦病毒感染可导致两种不同的临床结果：肾综合征出血热（HFRS）和汉坦病毒性心肺综合征（HCPS）。虽然这两种综合征都在呼吸道传播后发展，并与多器官衰竭和高死亡率相关，但对导致这些明显临床结果的机制知之甚少。因此，重要的是要确定哪些细胞类型和组织在人类发病机理的差异发展中起作用。这里，我们回顾了有关人类和储藏啮齿动物正汉坦病毒感染期间细胞向性及其在发病机理中的作用的当前知识。甲型汉坦病毒主要感染人的各种器官（肺，心脏，肾脏，肝脏和脾脏）的微血管内皮细胞（EC）。但是，在这篇综述中，我们证明了其他类型的细胞（例如，巨噬细胞，树突状细胞和肾小管上皮细胞）也被感染，并且可能在发病机理的早期阶段起作用。致病机理的关键驱动因素是血管通透性的提高，这可能是EC中病毒感染的直接作用，或者是试图清除病毒的免疫反应失衡的结果。未来的研究应侧重于确定器官特异性内皮细胞以及其他细胞类型的感染如何导致发病机理的作用。