Metagenomic Analysis of Fever, Thrombocytopenia and Leukopenia Syndrome (FTLS) in Henan Province, China: Discovery of a New Bunyavirus

PLoS Pathogens

Licheng Liu¹  Pengzhi Wang¹  Weijun Chen¹  Feng Mu¹  Xueyong Huang²  Haomin Chen²  Haifeng Wang²  Xiaoyan Tang²  Kai Kang²  Hong Ma²  Yanhua Du²  Bianli Xu²  Guohua Zhao³  Shiqiang Zhang³  Weili Wu⁴  Yuan Zhang⁴  Yinhui Yang⁵ 

[1] Beijing Genomics Institute in Wuhan, Wuhan, China;Center for Disease Control and Prevention of Henan Province, Zhengzhou, China;Center for Disease Control and Prevention of Xinyang City, Xinyang, China;Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China;State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China

关键词: Bunyaviruses;    Hepatitis B virus;    Rift Valley fever virus;    Crimean-Congo hemorrhagic fever virus;    Reverse transcriptase-polymerase chain reaction;    Fevers;    Hemorrhagic fever viruses;    Polymerase chain reaction;   

DOI  :  10.1371/journal.ppat.1002369

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Since 2007, many cases of fever, thrombocytopenia and leukopenia syndrome (FTLS) have emerged in Henan Province, China. Patient reports of tick bites suggested that infection could contribute to FTLS. Many tick-transmitted microbial pathogens were tested for by PCR/RT-PCR and/or indirect immunofluorescence assay (IFA). However, only 8% (24/285) of samples collected from 2007 to 2010 tested positive for human granulocytic anaplasmosis (HGA), suggesting that other pathogens could be involved. Here, we used an unbiased metagenomic approach to screen and survey for microbes possibly associated with FTLS. BLASTx analysis of deduced protein sequences revealed that a novel bunyavirus (36% identity to Tehran virus, accession: HQ412604) was present only in sera from FTLS patients. A phylogenetic analysis further showed that, although closely related to Uukuniemi virus of the Phlebovirus genus, this virus was distinct. The candidate virus was examined for association with FTLS among samples collected from Henan province during 2007–2010. RT-PCR, viral cultures, and a seroepidemiologic survey were undertaken. RT-PCR results showed that 223 of 285 (78.24%) acute-phase serum samples contained viral RNA. Of 95 patients for whom paired acute and convalescent sera were available, 73 had serologic evidence of infection, with 52 seroconversions and 21 exhibiting a 4-fold increase in antibody titer to the virus. The new virus was isolated from patient acute-phase serum samples and named Henan Fever Virus (HNF virus). Whole-genome sequencing confirmed that the virus was a novel bunyavirus with genetic similarity to known bunyaviruses, and was most closely related to the Uukuniemi virus (34%, 24%, and 29% of maximum identity, respectively, for segment L, M, S at maximum query coverage). After the release of the GenBank sequences of SFTSV, we found that they were nearly identical (>99% identity). These results show that the novel bunyavirus (HNF virus) is strongly correlated with FTLS.

【 授权许可】

CC BY