Andes virus transmission and pathogenesis in Chile

描述(申请人提供)：汉坦病毒是美国国立卫生研究院A类病原体。新世界汉坦病毒导致汉坦病毒心肺综合征(HCPS)，这是一种在北美和南美洲死亡率接近40%的疾病病例。虽然HCPS最先在北美得到承认，但在南美洲，HCPS是一个更大的问题，智利、阿根廷和巴西的HCPS累计病例和死亡人数远远超过美国。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。人类从感染病毒的啮齿动物身上感染了安第斯病毒(ANDV)，这是智利HCPS的病原体，但ANDV是唯一可能在人与人之间传播的汉坦病毒。在智利，这导致家庭病例聚集性，特别是在性伴侣中。 在第二次竞争更新中，第一个目标是完善对HCPS指示病例的研究，并前瞻性地研究他们的密切家庭接触者，以评估人与人之间传播的危险因素。风险因素将通过问卷调查和RT-PCR检测唾液、牙龈沟液、呼吸道和生殖器分泌物、血液和尿液ANDV的存在以及RT-PCR阳性样本的病毒培养来评估。第二个目标是通过深度测序来加强ANDV的分离和鉴定，以评估患者和啮齿动物的病毒变异谱，并使用补充方法促进复制能力强的病毒的恢复。第一个目标是确定在从啮齿动物传播到人类以及从人传播到人的过程中，是否存在影响特定ANDV变种选择的生理和遗传瓶颈。第二是确定可导致更有效的病毒传播和便利病毒特性的易于处理的方法。第三个目标是通过a)开发试验点和b)开发和验证高通量中和抗体测定来建立抗ANDV疫苗的评估能力。将在农村高危地区建立试验点，在那里将确定血清阳性率和疫苗可接受性。BSL-2检测的验证将包括DOM和他的同事开发的检测的转移，以及更费力的BSL-3病灶减少检测的比较结果。 相关性：安第斯病毒是一种汉坦病毒，它会导致一种严重的疾病，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，这些信息可以用于教育和预防。这项研究还将开发测试地点，在那里可以测试预防安第斯病毒感染的疫苗，并进行血液测试，以观察人们对疫苗接种是否有反应。

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.