Clinical characteristics and molecular epidemiology of hepatitis E in Shenzhen, China: a shift toward foodborne transmission of hepatitis E virus infection

Sridhar, Siddharth; Lo, Stephen T.H.; Xing, Fanfan; Yang, Jin; Yé, Haiyan; Chan, Jasper Fuk‐Woo; Teng, Jade L. L.; Huang, Chuiguo; Yip, Cyril C. Y.; Lau, Susanna K.P.; Woo, Patrick C. Y.

doi:10.1038/emi.2017.107

Cited by 37 publications

(38 citation statements)

References 26 publications

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“…So far, isolates of both HEV genotypes 3 and 4 have been isolated from pigs and hence are commonly known as swine HEV (23). In China, genotype 4 is the predominant HEV genotype found in pig herds (24,25).…”

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confidence: 99%

Characterization of Three Novel Linear Neutralizing B-Cell Epitopes in the Capsid Protein of Swine Hepatitis E Virus

Chen

Liu

Sun

et al. 2018

J Virol

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Hepatitis E virus (HEV) causes liver disease in humans and is thought to be a zoonotic infection, with domestic animals, including swine and rabbits, being a reservoir. One of the proteins encoded by the virus is the capsid protein. This is likely the major immune-dominant protein and a target for vaccination. Four monoclonal antibodies (MAbs), three novel, 1E4, 2C7, and 2G9, and one previously characterized, 1B5, were evaluated for binding to the capsid protein from genotype 4 swine HEV. The results indicated that DFCP, PSRPF, and EPTV peptides on the capsid protein comprised minimal amino acid sequence motifs recognized by 1E4, 2C7, and 2G9, respectively. The data suggested that 2C7 and 2G9 epitopes were partially exposed on the surface of the capsid protein. Truncated genotype 4 swine HEV capsid protein (sp239, amino acids 368 to 606) can exist in multimeric forms. Preincubation of swine HEV with 2C7, 2G9, or 1B5 before addition to HepG2 cells partially blocked sp239 cell binding and inhibited swine HEV infection. The study indicated that 2C7, 2G9, and 1B5 partially blocked swine HEV infection of rabbits better than 1E4 or normal mouse IgG. The cross-reactivity of antibodies suggested that capsid epitopes recognized by 2C7 and 2G9 are common to HEV strains infecting most host species. Collectively, MAbs 2C7, 2G9, and 1B5 were shown to recognize three novel linear neutralizing B-cell epitopes of genotype 4 HEV capsid protein. These results enhance understanding of HEV capsid protein structure to guide vaccine and antiviral design. Genotype 3 and 4 HEVs are zoonotic viruses. Here, genotype 4 HEV was studied due to its prevalence in human populations and pig herds in China. To improve HEV disease diagnosis and prevention, a better understanding of the antigenic structure and neutralizing epitopes of HEV capsid protein are needed. In this study, the locations of three novel linear B-cell recognition epitopes within genotype 4 swine HEV capsid protein were characterized. Moreover, the neutralizing abilities of three MAbs specific for this protein, 2C7, 2G9, and 1B5, were studied and Collectively, these findings reveal structural details of genotype 4 HEV capsid protein and should facilitate development of applications for the design of vaccines and antiviral drugs for broader prevention, detection, and treatment of HEV infection of diverse human and animal hosts.

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confidence: 99%

Characterization of Three Novel Linear Neutralizing B-Cell Epitopes in the Capsid Protein of Swine Hepatitis E Virus

Chen

Liu

Sun

et al. 2018

J Virol

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“…Although food-borne infections in Asian cities have been mainly linked to genotype 4 Jeong et al, 2017;Sridhar et al, 2017;Wibawa et al, 2004), except for China and Japan where genotypes 3 and 4 were both detected (Table S3), we identified only one genotype 4 human case. Quite clearly, our study shows genotype 3a to be the main aetiological agent for most of the indigenous HEV cases in Singapore.…”

Section: Non-residentmentioning

confidence: 85%

Seroepidemiology and genotyping of hepatitis E virus in Singapore reveal rise in number of cases and similarity of human strains to those detected in pig livers

Wong

Thean

et al. 2019

Zoonoses and Public Health

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Hepatitis E virus (HEV) causes 20 million infections worldwide yearly, of which only about 3.3 million are symptomatic. In developed Asian countries, HEV strains detected in human sera and in food sources were genetically similar, suggesting that indigenous HEV infections may be largely food‐borne. To assess the burden of hepatitis E in Singapore, we performed a seroepidemiologic study of the infection. Additionally, we carried out HEV genotyping on archived, residual HEV IgM‐positive serum samples collected between 2014 and 2016 (n = 449), and on pig liver samples (n = 36) purchased from wet markets and supermarkets. Our study shows a rise in hepatitis E incidence (IgM) from 1.7 to 4.1 cases per 100,000 resident population from 2012 to 2016 and an increase in hepatitis E IgG positivity rate among residents from 14% in 2007 to 35% in 2016. Other findings also suggest the epidemiology of hepatitis E in Singapore has shifted, from it being mainly a disease imported from the Indian subcontinent, to one that is now increasingly prevalent in our resident population. Genotypes obtained from 143 human samples identified the majority to be genotype 3 (n = 121), 21 to be genotype 1 and one to be genotype 4. Further phylogenetic analyses suggest genotype 3a to be the cause of indigenous infections in residents, which showed genetic similarity to the genotype 3a strains detected in pig livers. This link between the strains in the majority of human samples and those in pig livers consumed by the public suggests a possible food‐borne route of HEV infection in Singapore.

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“…The discrepancy between our study and the European studies is likely due to the genotype differences. Despite an outbreak of 1989 was cause by GT1 HEV in Xinjiang province, China, the predominant circulating genotype in China has shifted towards GT4 over the decades, with occasional GT1 cases [16][17][18][19][20]. Several sporadic cases of neurological injury that possibly linked to HEV infection have been documented in China [12,[21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Hepatitis E Virus Infection in Acute Non-Traumatic Neuropathy: A Large Prospective Case-Control Study in China

Wang¹,

Wang

et al. 2018

SSRN Journal

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Neurological manifestations are potentially associated with hepatitis E virus (HEV) infection in Europe, mainly attributed to genotype (GT) 3 HEV infection. In this study, we determined the frequency and causal relationship of HEV in patients with non-traumatic neurological disorders in China, where GT4 HEV is prevalent. 1117 consecutive patients diagnosed with neurological illnesses in a hospital of eastern China and 1475 healthy controls who took routine examination in the same hospital were tested for HEV by serology and molecular methods. Anti-HEV IgM antibodies were detectable in 6 (0.54%) of the patients and 10 (0.68%) of the healthy controls (P = 0.651). Serum HEV RNA was detected in all of the 16 individuals with positive anti-HEV IgM. The six patients with HEV infection included two viral encephalitis, two posterior circulation ischemia, one peripheral neuropathy and one Guillian-Barré syndrome. They had no symptoms of acute viral hepatitis except two patients of viral encephalitis that showed mildly transaminitis. Additional, 39.51% patients and 35.63% controls without acute HEV infection were positive for anti-HEV IgG (P = 0.144). Anti-HEV IgG positivity was more frequent in male and elderly in both the patients and control groups, but unrelated to the incidence of any non-traumatic neurological illness, hospital stay or treatment outcome, except linking to better outcome of hemorrhagic stroke disease. These data demonstrated that HEV appears not to contribute to acute neurological disorders in China. Nevertheless, we cannot exclude a possible causative role, suggesting that testing HEV in this population, especially in situations of unexplained deregulated liver function would be warranted.a Student t-test for normally distributed continuous variables whereas other continuous variables were expressed in median (interquartile range [IQR]); the data with skewed distribution were compared using the Mann-Whitney U test; Chi-squared or the Fisher's exact test for categorical variables with excepted cell sizes less than five were used. b There is no treatment failure patient in both anti-HEV IgG positive and negative cohorts.Y. Wang et al. / EBioMedicine xxx (xxxx) xxx-xxx

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Clinical characteristics and molecular epidemiology of hepatitis E in Shenzhen, China: a shift toward foodborne transmission of hepatitis E virus infection

Cited by 37 publications

References 26 publications

Characterization of Three Novel Linear Neutralizing B-Cell Epitopes in the Capsid Protein of Swine Hepatitis E Virus

Characterization of Three Novel Linear Neutralizing B-Cell Epitopes in the Capsid Protein of Swine Hepatitis E Virus

Seroepidemiology and genotyping of hepatitis E virus in Singapore reveal rise in number of cases and similarity of human strains to those detected in pig livers

Hepatitis E Virus Infection in Acute Non-Traumatic Neuropathy: A Large Prospective Case-Control Study in China

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