Easterbrook Judith D, Klein Sabra L
The W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
PLoS Pathog. 2008 Nov;4(11):e1000172. doi: 10.1371/journal.ppat.1000172. Epub 2008 Nov 28.
Hantaviruses, similar to several emerging zoonotic viruses, persistently infect their natural reservoir hosts, without causing overt signs of disease. Spillover to incidental human hosts results in morbidity and mortality mediated by excessive proinflammatory and cellular immune responses. The mechanisms mediating the persistence of hantaviruses and the absence of clinical symptoms in rodent reservoirs are only starting to be uncovered. Recent studies indicate that during hantavirus infection, proinflammatory and antiviral responses are reduced and regulatory responses are elevated at sites of increased virus replication in rodents. The recent discovery of structural and non-structural proteins that suppress type I interferon responses in humans suggests that immune responses in rodent hosts could be mediated directly by the virus. Alternatively, several host factors, including sex steroids, glucocorticoids, and genetic factors, are reported to alter host susceptibility and may contribute to persistence of hantaviruses in rodents. Humans and reservoir hosts differ in infection outcomes and in immune responses to hantavirus infection; thus, understanding the mechanisms mediating viral persistence and the absence of disease in rodents may provide insight into the prevention and treatment of disease in humans. Consideration of the coevolutionary mechanisms mediating hantaviral persistence and rodent host survival is providing insight into the mechanisms by which zoonotic viruses have remained in the environment for millions of years and continue to be transmitted to humans.
汉坦病毒与几种新出现的人畜共患病毒相似，能持续感染其自然宿主，且不会引发明显的疾病症状。病毒传播到偶然感染的人类宿主身上会导致发病和死亡，这是由过度的促炎和细胞免疫反应介导的。介导汉坦病毒持续存在以及在啮齿动物宿主中不出现临床症状的机制才刚刚开始被揭示。最近的研究表明，在汉坦病毒感染期间，啮齿动物体内病毒复制增加的部位，促炎和抗病毒反应会减弱，而调节反应会增强。最近发现的抑制人类I型干扰素反应的结构和非结构蛋白表明，啮齿动物宿主中的免疫反应可能直接由病毒介导。另外，据报道，包括性类固醇、糖皮质激素和遗传因素在内的几种宿主因素会改变宿主易感性，并可能有助于汉坦病毒在啮齿动物中持续存在。人类和宿主在感染结果以及对汉坦病毒感染的免疫反应方面存在差异；因此，了解介导病毒持续存在以及啮齿动物不发病的机制可能会为人类疾病的预防和治疗提供思路。对介导汉坦病毒持续存在和啮齿动物宿主存活的共同进化机制的思考，正在为了解人畜共患病毒在环境中存在数百万年并继续传播给人类的机制提供思路。
