Andes virus transmission and pathogenesis in Chile

性状（由申请方提供）：汉坦病毒是NIH A类病原体。新世界汉他病毒引起汉他病毒心肺综合征（HCPS），这是一种在北美和南美致死率接近40%的疾病病例。虽然HCPS首先在北美被认识到，但它在南美洲是一个更大的问题，智利、阿根廷和巴西的HCPS病例和死亡累积人数远远超过美国。智利的人口是美国的二十分之一，智利报告的病例总数（604例）比美国（约500例）多，智利每年发生的病例和死亡人数比美国多。人类获得安第斯山脉病毒（ANDV），在智利HCPS的病原体，从病毒感染的啮齿动物，但ANDV是唯一的汉他病毒，然后可以在人与人之间传播。在智利，这导致家庭病例聚集，特别是在性伴侣之间。 在第二次竞争性更新中，第一个目标是改进对HCPS指示病例的研究，并前瞻性地研究其密切的家庭接触者，以评估人与人之间传播的风险因素。将通过问卷调查和通过RT-PCR检测唾液、龈沟液、呼吸道和生殖器分泌物、血液和尿液中ANDV的存在以及通过RT-PCR阳性样本中的病毒培养来评估风险因素。第二个目的是使用深度测序来增强ANDV分离和表征，以评估来自患者和啮齿动物的病毒变体谱，并使用互补方法来促进复制能力病毒的回收。第一个目标是确定是否存在生理和遗传瓶颈影响特定ANDV变体在从啮齿动物到人和从人到人的传播中的选择。第二是确定易于处理的方法，导致更有效的病毒繁殖和促进病毒表征。第三个目的是通过a）开发试验地点和B）开发和验证用于测量中和抗体的高通量测定法来建立抗ANDV疫苗评价能力。将在农村高风险地区建立试验点，以确定血清阳性率和疫苗可接受性。BSL-2测定法的验证将包括转移Doms及其同事开发的测定法，并比较更费力的BSL-3病灶减少测定法的结果。 相关性：安第斯山脉病毒是一种汉他病毒，可引起一种严重的疾病，导致近40%的感染者死亡。这项研究旨在帮助我们了解病毒是如何传播的，这些信息可用于教育和预防。该研究还将开发试验场所，在那里可以测试预防安第斯山脉病毒感染的疫苗，并进行血液测试，以确定人们是否对疫苗接种有反应。

DESCRIPTION (provided by applicant): Hantaviruses are NIH category A pathogens. New World hantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a disease case with fatality rates that approach 40% in both North and South America. Although first recognized in North America, HCPS is a much larger problem in South America where cumulative numbers of cases and deaths from HCPS in Chile, Argentina and Brazil far exceed those in the United States. In a population one-twentieth that of the US, more total cases (604) have been in reported in Chile than in the US (~500 cases), and more cases and deaths occur each year in Chile than in the US. Humans acquire Andes virus (ANDV), the etiologic agent of HCPS in Chile, from virus-infected rodents, but ANDV is the only hantavirus that may then be transmitted from person to person. In Chile, this results in household case clusters, particularly among sex partners. In this second competitive renewal, the first aim is to refine the study of index cases with HCPS and prospectively study their close household contacts to evaluate risk factors for person to person transmission. Risk factors will be assessed through a questionnaire and through testing saliva, gingival crevicular fluid, respiratory and genital secretions, blood and urine for the presence of ANDV by RT-PCR and by viral culture in RT-PCR positive samples. The second aim is to enhance ANDV isolation and characterization using deep sequencing to evaluate the spectrum of viral variants from patients and rodents and use complementary approaches to facilitate recovery of replication-competent virus. The first goal is to determine whether there are physiological and genetic bottlenecks influencing the selection of particular ANDV variants in transmission from rodents to humans and from human to human. The second is to identify tractable approaches that lead to more efficient virus propagation and facilitate virus characterization. The third aim is to establish anti-ANDV vaccine evaluation capacity by a) developing test sites and b) developing and validating a high throughput assay for measurement of neutralizing antibody. Test sites will be established in rural, high-risk areas where both seroprevalence and vaccine acceptability will be determined. Validation of the BSL-2 assay will include transfer of an assay developed by Doms and colleagues and comparison results from the more laborious BSL-3 focus reduction assay. RELEVANCE: Andes virus is a hantavirus that causes a serious disease that kills almost 40% of those who become infected. This research is designed to help us learn how the virus is transmitted, information that could be used for education and prevention. The research will also develop test sites where a vaccine to prevent Andes virus infection could be tested and a blood test to see whether people respond to vaccination.