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West Nile virus (WNV) was first isolated in mainland China from mosquitoes in Jiashi County, Kashgar Region, Xinjiang in 2011, following local outbreaks of viral meningitis and encephalitis caused by WNV. To elaborate the epidemiological characteristics of the WNV, surveillance of WNV infection in Kashgar Region, Xinjiang from 2013 to 2016 were carried out. Blood and CSF samples from surveillance human cases, blood of domestic chicken, cattle, sheep and mosquitoes in Kashgar Region were collected and detected. There were human 65 WNV Immunoglobulin M (IgM) antibody positive cases by ELISA screening, 6 confirmed WNV cases by the plaque reduction neutralization test (PRNT) screening. These cases occurred mainly concentrated in August to September of each year, and most of them were males. WNV-neutralizing antibodies were detected in both chickens and sheep, and the positive rates of neutralizing antibodies were 15.5% and 1.78%, respectively. A total of 15,637 mosquitoes were collected in 2013–2016, with Culex pipiens as the dominant mosquito species. Four and 1 WNV-positive mosquito pools were detected by RT-qPCR in 2013 and 2016 respectively. From these data, we can confirm that Jiashi County may be a natural epidemic foci of WNV disease, the trend highlights the routine virology surveillance in WNV surveillance cases, mosquitoes and avian should be maintained and enhanced to provide to prediction and early warning of outbreak an epidemic of WNV in China. [ABSTRACT FROM AUTHOR]