Jamestown Canyon virus in Massachusetts: clinical case series and vector screening

Jamestown Canyon virus (JCV) is a neuroinvasive arbovirus that is found throughout North America and increasingly recognized as a public health concern. From 2004 to 2012, an average of 1.7 confirmed cases were reported annually in the United States, whereas from 2013 to 2018 this figure increased over seventeen-fold to 29.2 cases per year. The rising number of reported human infections highlights the need for better understanding of the clinical manifestations and epidemiology of JCV. Here, we describe nine patients diagnosed with neuroinvasive JCV infection in Massachusetts from 2013, the year of the first reported case in the state, to 2017. Because current diagnostic testing relies on serology, which is complicated by cross-reactivity with related orthobunyaviruses and can be negative in immunosuppressed patients, we developed and evaluated an RT-qPCR assay for detection of JCV RNA. We tested this on the available archived serum from two patients, but did not detect viral RNA. JCV is transmitted by multiple mosquito species and its primary vector in Massachusetts is unknown, so we additionally applied the RT-qPCR assay and confirmatory RNA sequencing to assess JCV prevalence in a vector candidate, <i>Ochlerotatus canadensis</i>. We identified JCV in 0.6% of mosquito pools, a similar prevalence to neighboring Connecticut. We assembled the first Massachusetts JCV genome directly from a mosquito sample, finding high identity to JCV isolates collected over a 60-year period. Further studies are needed to reconcile the low vector prevalence and low rate of viral evolutionary change with the increasing number of reported cases.

詹姆斯敦峡谷病毒（Jamestown Canyon virus, JCV）是一种侵入神经性虫媒病毒，广泛分布于北美大陆，且日益被认定为公共卫生领域的重点关注病原体。2004年至2012年间，美国年均报告确诊病例1.7例；而2013年至2018年，该数值增长逾17倍，达到年均29.2例。报告的人类感染病例数持续攀升，凸显了深入解析该病毒临床表现与流行病学特征的迫切需求。本研究纳入了2013年至2017年间马萨诸塞州确诊的9例侵入神经性JCV感染患者——2013年正是该州首例JCV感染病例的报告年份。由于当前主流的JCV诊断检测依赖血清学方法，该方法存在与相关正布尼亚病毒（orthobunyavirus）发生交叉反应的局限，且在免疫功能低下患者中可能呈现假阴性结果，因此我们开发并评估了一种用于检测JCV RNA的逆转录定量聚合酶链反应（reverse transcription quantitative polymerase chain reaction, RT-qPCR）检测体系。我们对2名患者的存档血清样本开展了该检测，但未检出病毒RNA。JCV可通过多种蚊类物种传播，但其在马萨诸塞州的主要传播媒介仍未明确，因此我们额外应用该RT-qPCR检测体系与验证性RNA测序技术，对候选媒介加拿大伊蚊（Ochlerotatus canadensis）的JCV流行率进行了评估。我们在0.6%的蚊群混合样本中检出了JCV，其流行率与邻近的康涅狄格州相近。我们直接从蚊样本中组装得到马萨诸塞州首例JCV全基因组序列，发现其与过去60年间采集的JCV分离株具有高度同源性。最后，仍需开展进一步研究，以阐明为何媒介携带率与病毒进化速率均处于较低水平，但报告的感染病例数却持续增长。