Characterizing a Murine Model for Astrovirus Using Viral Isolates from Persistently Infected Immunocompromised Mice
Characterizing a Murine Model for Astrovirus Using Viral Isolates from Persistently Infected Immunocompromised Mice
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DOI：
10.1128/jvi.00223-19
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发表时间：
2019-07-01
影响因子：
5.4
通讯作者：
Schultz-Cherry, Stacey
中科院分区：
文献类型：
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作者：
Cortez, Valerie;Sharp, Bridgett;Schultz-Cherry, Stacey
人星状病毒是单链RNA肠道病毒，其引起从无症状感染到全身性胃肠道外传播的疾病谱;然而，它们是特征最少的肠道病毒之一，并且缺乏充分表征的小动物模型。发现免疫功能低下的小鼠通过多种接种途径对人星状病毒感染具有抗性，我们的研究旨在确定小鼠星状病毒（MuAstV）是否可用于模拟人星状病毒疾病。我们用从免疫功能低下的小鼠中分离的MuAstV实验性感染野生型小鼠，发现在整个胃肠道（包括胃）中都检测到该病毒，但与腹泻无关。在肺部也检测到了病毒。虽然最近断奶的小鼠中病毒水平较高，但雄性和雌性成年小鼠中的水平相似。使用从不同免疫功能低下小鼠品系中分离的两种不同病毒，我们观察到野生型小鼠感染持续时间（3周与10周）的病毒株特异性差异，表明供体小鼠的宿主内免疫压力塑造了免疫活性受体宿主中的病毒动力学。两种病毒株引起最低限度的病理和缺乏持续的免疫力。总之，MuAstV代表了一个有用的模型，用于研究无症状的人类感染和深入了解星状病毒的发病机制和immunity.IMPORTANCE星状病毒是广泛存在于鸟类和哺乳动物，然而，鲜为人知的发病机制和免疫反应的病毒，由于缺乏一个良好的特点小动物模型。在这里，我们描述了两种不同的鼠星状病毒株，引起免疫活性小鼠感染，反映了人类无症状感染的方面，包括最小的病理和短暂的免疫。然而，我们注意到，感染的持续时间在菌株之间差异很大，突出了这些病毒的一个重要方面，这是以前没有认识到的。鼠星状病毒的普遍存在的性质和多样性，加上持续的再感染的可能性，提高了病毒干扰其他小鼠疾病模型的可能性。
Human astroviruses are single-stranded RNA enteric viruses that cause a spectrum of disease ranging from asymptomatic infection to systemic extragastrointestinal spread; however, they are among the least-characterized enteric viruses, and there is a lack of a well-characterized small animal model. Finding that immunocompromised mice were resistant to human astrovirus infection via multiple routes of inoculation, our studies aimed to determine whether murine astrovirus (MuAstV) could be used to model human astrovirus disease. We experimentally infected wild-type mice with MuAstV isolated from immunocompromised mice and found that the virus was detected throughout the gastrointestinal tract, including the stomach, but was not associated with diarrhea. The virus was also detected in the lung. Although virus levels were higher in recently weaned mice, the levels were similar in male and female adult mice. Using two distinct viruses isolated from different immunocompromised mouse strains, we observed virus strain-specific differences in the duration of infection (3 versus 10 weeks) in wild-type mice, indicating that the within-host immune pressure from donor mice shaped the virus kinetics in immunocompetent recipient hosts. Both virus strains elicited minimal pathology and a lack of sustained immunity. In summary, MuAstV represents a useful model for studying asymptomatic human infection and gaining insight into the astrovirus pathogenesis and immunity.IMPORTANCE Astroviruses are widespread in both birds and mammals; however, little is known about the pathogenesis and the immune response to the virus due to the lack of a well-characterized small-animal model. Here we describe two distinct strains of murine astrovirus that cause infections in immunocompetent mice that mirror aspects of asymptomatic human infections, including minimal pathology and short-lived immunity. However, we noted that the duration of infection differed greatly between the strains, highlighting an important facet of these viruses that was not previously appreciated. The ubiquitous nature and diversity of murine astroviruses coupled with the continuous likelihood of reinfection raise the possibility of viral interference with other mouse models of disease.