title: Metagenomic analysis of fever, thrombocytopenia and leukopenia syndrome (FTLS) in Henan Province, China: discovery of a new bunyavirus.
abstract: 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.
authors: Center for Disease Control and Prevention of Henan Province, Zhengzhou, China.
authors: Bianli
authors: B
authors: Xu
authors: Licheng
authors: L
authors: Liu
authors: Xueyong
authors: X
authors: Huang
authors: Hong
authors: H
authors: Ma
authors: Yuan
authors: Y
authors: Zhang
authors: Yanhua
authors: Y
authors: Du
authors: Pengzhi
authors: P
authors: Wang
authors: Xiaoyan
authors: X
authors: Tang
authors: Haifeng
authors: H
authors: Wang
authors: Kai
authors: K
authors: Kang
authors: Shiqiang
authors: S
authors: Zhang
authors: Guohua
authors: G
authors: Zhao
authors: Weili
authors: W
authors: Wu
authors: Yinhui
authors: Y
authors: Yang
authors: Haomin
authors: H
authors: Chen
authors: Feng
authors: F
authors: Mu
authors: Weijun
authors: W
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002043:Bunyaviridae / Q000235:genetics* / Q000302:isolation & purification; D002044:Bunyaviridae Infections / Q000821:virology*; D002681:China; D021821:Communicable Diseases, Emerging / Q000821:virology*; D005260:Female; D005334:Fever; D006801:Humans; D007970:Leukopenia; D008297:Male; D056186:Metagenomics; D008875:Middle Aged; D008969:Molecular Sequence Data; D016856:Phlebovirus / Q000235:genetics; D016036:Seroepidemiologic Studies; D013577:Syndrome; D013921:Thrombocytopenia