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Fever with thrombocytopenia associated with a novel bunyavirus in China.

ABSTRACT: Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing.We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolate the causal pathogen by inoculation of cell culture and for detection of viral RNA on polymerase-chain-reaction assay. The pathogen was characterized on electron microscopy and nucleic acid sequencing. We used enzyme-linked immunosorbent assay, indirect immunofluorescence assay, and neutralization testing to analyze the level of virus-specific antibody in patients' serum samples.We isolated a novel virus, designated SFTS bunyavirus, from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction. RNA sequence analysis revealed that the virus was a newly identified member of the genus phlebovirus in the Bunyaviridae family. Electron-microscopical examination revealed virions with the morphologic characteristics of a bunyavirus. The presence of the virus was confirmed in 171 patients with SFTS from six provinces by detection of viral RNA, specific antibodies to the virus in blood, or both. Serologic assays showed a virus-specific immune response in all 35 pairs of serum samples collected from patients during the acute and convalescent phases of the illness.A novel phlebovirus was identified in patients with a life-threatening illness associated with fever and thrombocytopenia in China. (Funded by the China Mega-Project for Infectious Diseases and others.).

SUBMITTER: Yu XJ

PROVIDER: S-EPMC3113718 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Fever with thrombocytopenia associated with a novel bunyavirus in China.

Yu Xue-Jie XJ Liang Mi-Fang MF Zhang Shou-Yin SY Liu Yan Y Li Jian-Dong JD Sun Yu-Lan YL Zhang Lihong L Zhang Quan-Fu QF Popov Vsevolod L VL Li Chuan C Qu Jing J Li Qun Q Zhang Yan-Ping YP Hai Rong R Wu Wei W Wang Qin Q Zhan Fa-Xian FX Wang Xian-Jun XJ Kan Biao B Wang Shi-Wen SW Wan Kang-Lin KL Jing Huai-Qi HQ Lu Jin-Xin JX Yin Wen-Wu WW Zhou Hang H Guan Xu-Hua XH Liu Jia-Fa JF Bi Zhen-Qiang ZQ Liu Guo-Hua GH Ren Jun J Wang Hua H Zhao Zhuo Z Song Jing-Dong JD He Jin-Rong JR Wan Tao T Zhang Jing-Shan JS Fu Xiu-Ping XP Sun Li-Na LN Dong Xiao-Ping XP Feng Zi-Jian ZJ Yang Wei-Zhong WZ Hong Tao T Zhang Yu Y Walker David H DH Wang Yu Y Li De-Xin DX

The New England journal of medicine 20110316 16

<h4>Background</h4>Heightened surveillance of acute febrile illness in China since 2009 has led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with an unknown cause. Infection with Anaplasma phagocytophilum has been suggested as a cause, but the pathogen has not been detected in most patients on laboratory testing.<h4>Methods</h4>We obtained blood samples from patients with the case definition of SFTS in six provinces in China. The blood samples were used to isolat ...[more]

PMID: 21410387

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Project description: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.

Dataset Information

Fever with thrombocytopenia associated with a novel bunyavirus in China.

Publications

Fever with thrombocytopenia associated with a novel bunyavirus in China.

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