title: Seroprevalence and evolutionary dynamics of genotype 4 hepatitis E virus in Shandong Province, China.
abstract: OBJECTIVE
  To investigate the seroprevalence and evolutionary dynamics of hepatitis E virus (HEV) and assess the ancestor of HEVs in China's Shandong Province.
  
  
  METHODS
  A total of 2028 serum, 60 fecal and 82 bile samples were collected from the general human population, patients and swine, respectively. This seroepidemiological study was conducted using an immunnosorbent assay and HEV RNA was detected by the reverse transcription-nested polymerase chain reaction (RT-nPCR) method. Complete genome sequences of the prevalent strains (CH-YT-HEV01, CH-YT-HEV02 and CH-YT-sHEV01) were determined, and the sequences were analyzed phylogenetically. In addition, the evolutionary dynamics of three HEV isolates were determined using the framework of coalescent analysis in the program package BEAST, and the time of the most recent common ancestors (TMRCAs) of China-indigenous genotype 4 HEV isolates was calculated.
  
  
  RESULTS
  The overall viral burden in the general human population was 0.1%, and the positive rates of anti-HEV IgG and IgM in the serum specimens were 25.1% (509/2028) and 2.3% (51/2028), respectively. In addition, IgG positivity increased with age. The phylogenetic analysis based on the full-length nucleotide sequences showed that the strain CH-YT-HEV02 was directly related to CH-YT-sHEV01 with a 94% identity, suggesting that they were involved in cross-species transmission. The isolate CH-YT-HEV01 was close to HB-3 and CHN-SD-sHEV with a bootstrap value of 100%, sharing a 96.1%-96.4% identity with each other. Surprisingly, the HB-3 strain was a representative strain prevalent in swine in Hubei, and the isolate CHN-SD-sHEV was obtained from swine in Shandong in a previous report. TMRCA for the clade of CH-YT-HEV01 and HB-3 was 2003, which was consistent with the TMRCA for the clade of CHN-SD-sHEV and HB-3, and they were both earlier than the TMRCA for the clade of CH-YT-HEV01 and CHN-SD-sHEV (2004).
  
  
  CONCLUSIONS
  The strains CH-YT-HEV01, CHN-SD-sHEV and HB-3 are involved in trans-regional transmission, and the ancestors of HEVs in Shandong come from Hubei Province.
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Dong
authors: D
authors: Yang
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Mei
authors: M
authors: Jiang
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Min
authors: M
authors: Jin
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Zhi-Gang
authors: ZG
authors: Qiu
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Zhi-Qiang
authors: ZQ
authors: Shen
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Wei-Hong
authors: WH
authors: Cui
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Da-Ning
authors: DN
authors: Wang
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Lian-Feng
authors: LF
authors: Gong
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Bo
authors: B
authors: Li
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Xin-Wei
authors: XW
authors: Wang
authors: Dong Yang, Min Jin, Zhi-Gang Qiu, Zhi-Qiang Shen, Da-Ning Wang, Xin-Wei Wang, Jun-Wen Li, Department of Environment and Health, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors: Jun-Wen
authors: JW
authors: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001646:Bile / Q000821:virology; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D003430:Cross-Sectional Studies; D019143:Evolution, Molecular; D005243:Feces / Q000821:virology; D005260:Female; D005838:Genotype; D006508:Hepatitis Antibodies / Q000097:blood; D016751:Hepatitis E / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000635:transmission / Q000821:virology*; D016752:Hepatitis E virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D010641:Phenotype; D010802:Phylogeny; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood; D016036:Seroepidemiologic Studies; D013552:Swine; D019562:Viral Load; D055815:Young Adult; D015047:Zoonoses
chemical_list: D015415:Biomarkers; D006508:Hepatitis Antibodies; D007074:Immunoglobulin G; D012367:RNA, Viral
keywords: Cross-species transmission; Evolutionary dynamics; Hepatitis E virus; Trans-regional transmission; Zoonotic