Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques
Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques
复制标题
戊型肝炎病毒新基因型从双峰驼到食蟹猴的传播
DOI：
10.1128/jvi.02014-18
复制
发表时间：
2019-04-01
影响因子：
5.4
通讯作者：
Wang, Ling
中科院分区：
文献类型：
--
作者：
Wang, Lin;Teng, Jade L. L.;Wang, Ling
据估计，世界上三分之一的人口接触过戊型肝炎病毒(HEV)。在发达国家和中国，人畜共患病的HEV毒株几乎是所有急性和慢性HEV感染病例的罪魁祸首。研究新的HEV毒株的人畜共患病潜力总是迫在眉睫的。2016年，我们在双峰驼身上发现了一种新的HEV基因型HEV8，但该病毒的流行病学、人畜共患病潜力和致病性尚不清楚。在本研究中，我们证明了HEV8在中国的多个地区流行，并能够感染人类的替代品食蟹猴，构成人畜共患病的高风险。观察慢性肝炎、全身感染和肾脏病理改变。总体而言，这些数据表明HEV8具有很高的人畜共患病传播潜力。考虑到双峰驼作为家畜的重要性，应对骆驼肉和奶消费者等危险群体进行HEV8感染筛查。摘要戊型肝炎病毒(HEV)是人畜共患病，是世界范围内急性病毒性肝炎的主要原因。最近，我们在新疆双峰驼中发现了一种新的戊型肝炎病毒8型，中国。然而，HEV8的流行病学、致病性和人畜共患潜力尚不清楚。在这里，我们介绍了戊型肝炎病毒8型在中国的流行情况，并调查了其在食蟹猴中的致病性和跨物种传播。采用逆转录聚合酶链式反应(RT-PCR)对采自中国地区4个省区的双峰驼新鲜粪便和乳样进行HEVRNA检测。HEV8阳性样本被用来接种两只食蟹猴，以检查跨物种感染的可能性。通过检测研究期间的戊型肝炎病毒标志物和肝功能，以及接种后3、13和25 周的肝组织病理学检查来分析HEV8型肝炎病毒的致病性。用逆转录定量聚合酶链式反应(RT-qPCR)和免疫荧光方法检测肝外复制情况。中国双峰驼中HEV8RNA总感染率为1.4%(4/2 95)，中国地区有3个省区检出阳性标本。组织病理学证实了这两只猴子的急性和慢性HEV8感染。多个组织中HEV RNA和ORF2蛋白呈阳性。本文观察了慢性肝炎猴的肾脏病理变化。全基因组测序显示，与骆驼的粪便样本相比，两只猴子的粪便样本中只有1到3个HEV8突变。HEV8正在中国的多个地区传播。感染HEV8的两只猴子引起慢性和系统性感染，表明HEV8具有很高的人畜共患病风险。重要性据估计，世界上三分之一的人口曾接触过戊型肝炎病毒(HEV)。在发达国家和中国，人畜共患病的HEV毒株几乎是所有急性和慢性HEV感染病例的罪魁祸首。研究新的HEV毒株的人畜共患病潜力总是迫在眉睫的。2016年，我们在双峰驼身上发现了一种新的HEV基因型HEV8，但该病毒的流行病学、人畜共患病潜力和致病性尚不清楚。在本研究中，我们证明了HEV8在中国的多个地区流行，并能够感染人类的替代品食蟹猴，构成人畜共患病的高风险。观察慢性肝炎、全身感染和肾脏病理改变。总体而言，这些数据表明HEV8具有很高的人畜共患病传播潜力。考虑到双峰驼作为家畜的重要性，应对骆驼肉和奶消费者等危险群体进行HEV8感染筛查。
It is estimated that one-third of the world population have been exposed to hepatitis E virus (HEV). In developed countries and China, zoonotic HEV strains are responsible for almost all acute and chronic HEV infection cases. It is always of immediate interest to investigate the zoonotic potential of novel HEV strains. In 2016, we discovered a novel HEV genotype, HEV8, in Bactrian camels, but the epidemiology, zoonotic potential, and pathogenicity of the virus were unknown. In the present study, we demonstrated that HEV8 was circulating in multiple regions in China and was capable of infecting cynomolgus macaques, a surrogate for humans, posing high risk of zoonosis. Chronic hepatitis, systemic infection, and renal pathology were observed. Collectively, these data indicate that HEV8 exhibits a high potential for zoonotic transmission. Considering the importance of Bactrian camels as livestock animals, risk groups, such as camelid meat and milk consumers, should be screened for HEV8 infection. ABSTRACT Hepatitis E virus (HEV) is zoonotic and a major cause of acute viral hepatitis worldwide. Recently, we identified a novel HEV genotype 8 (HEV8) in Bactrian camels in Xinjiang, China. However, the epidemiology, pathogenicity, and zoonotic potential of HEV8 are unclear. Here, we present the prevalence of HEV8 in China and investigate its pathogenicity and cross-species transmission in cynomolgus macaques. Fresh fecal and milk samples from Bactrian camels collected from four provinces/regions in China were screened for HEV RNA by reverse transcriptase PCR (RT-PCR). An HEV8-positive sample was used to inoculate two cynomolgus macaques to examine the potential for cross-species infection. The pathogenicity of HEV8 was analyzed by testing HEV markers and liver function during the study period and histopathology of liver biopsy specimens at 3, 13, and 25 weeks postinoculation. Extrahepatic replication was tested by using reverse transcriptase quantitative PCR (RT-qPCR) and immunofluorescence assays. The overall prevalence of HEV8 RNA in Chinese Bactrian camels was 1.4% (4/295), and positive samples were found in three different provinces/regions in China. Histopathology confirmed acute and chronic HEV8 infections in the two monkeys. Multiple tissues were positive for HEV RNA and ORF2 proteins. Renal pathology was observed in the monkey with chronic hepatitis. Whole-genome sequencing showed only 1 to 3 mutations in the HEV8 in the fecal samples from the two monkeys compared to that from the camel. HEV8 is circulating in multiple regions in China. Infection of two monkeys with HEV8 induced chronic and systemic infections, demonstrating the high potential zoonotic risk of HEV8. IMPORTANCE It is estimated that one-third of the world population have been exposed to hepatitis E virus (HEV). In developed countries and China, zoonotic HEV strains are responsible for almost all acute and chronic HEV infection cases. It is always of immediate interest to investigate the zoonotic potential of novel HEV strains. In 2016, we discovered a novel HEV genotype, HEV8, in Bactrian camels, but the epidemiology, zoonotic potential, and pathogenicity of the virus were unknown. In the present study, we demonstrated that HEV8 was circulating in multiple regions in China and was capable of infecting cynomolgus macaques, a surrogate for humans, posing high risk of zoonosis. Chronic hepatitis, systemic infection, and renal pathology were observed. Collectively, these data indicate that HEV8 exhibits a high potential for zoonotic transmission. Considering the importance of Bactrian camels as livestock animals, risk groups, such as camelid meat and milk consumers, should be screened for HEV8 infection.