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| 1 | Hemorrhagic Fever with Renal Syndrome — Liaoning Province, China, 1999−2018显示文摘Summary What is already known on this topic?Hemorrhagic fever with renal syndrome(HFRS)is endemic in Liaoning Province.Both Seoul and Hantaan virus are circulating in rodents,and epidemic outbreaks and sporadic cases have been recorded every year since the disease was recognized. | Cui Shang Yingwei Sun Qiangling Yin Xiaoxia Huang Xuesheng Liu Quanfu Zhang Lingling Mao Chuan Li Aqian Li Qin Wang Lina Sun Mifang Liang Shiwen Wang Dexin Li Jiandong Li | 2020 | China CDC weekly2020，2，20： | 6 |
| 2 | Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants显示文摘Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing antibodies.This highlights a critical need to discover new therapeutic agents to overcome the variants mutations.Despite the availability of vaccines against coronavirus disease 2019(COVID-19),the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-Co V-2 variants infection.Here,we show that the nasal delivery of two previously characterized broadly neutralizing antibodies(F61 and H121)protected K18-h ACE2 mice against lethal challenge with SARS-Co V-2 variants.The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain(WIV04)and multiple variants,including beta(B.1.351),delta(B.1.617.2),and omicron(B.1.1.529)at 200or 1000 TCID_(50),and the minimum antibody administration doses(5-1.25 mg/kg body weight)were also evaluated with delta and omicron challenge.Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight,and corresponding mice lung viral RNA showed negative,with almost all alveolar septa and cavities remaining normal.Furthermore,low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants,whereas the F61/H121 combination showed excellent results against omicron infection.Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-Co V-2 variants infection. | Jia Lu Qiangling Yin Rongjuan Pei Qiu Zhang Yuanyuan Qu Yongbing Pan Lina Sun Ding Gao Cuiqin Liang Jingwen Yang Wei Wu Jiandong Li Zongqiang Cui Zejun Wang Xinguo Li Dexin Li Shiwen Wang Kai Duan Wuxiang Guan Mifang Liang Xiaoming Yang | 2022 | Virologica Sinica2022，37，2： | 4 |
| 3 | Molecular evolution and genetic diversity analysis of SFTS virus based on next-generation sequencing显示文摘SFTS virus(SFTSV)is a novel bunyavirus,which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome(SFTS)in China in 2009,and was now prevalent in at least 25 provinces in China.SFTS was subsequently identified in South Korea and Japan in 2012.To explore themolecular evolution and genetic characteristics of this newly identified pathogen,we reported 72 whole genome sequences of SFTSV,and built a dataset of SFTSV genome sequences containing 292 L-segment,302 M-segment and 502 S-segment.We clearly divided SFTSV into six genotypes,Genotype A-F.It was found that genotype F was the dominant epidemic genotype of Japan,South Korea,and Zhejiang province of China.The coalescent analysis supported that SFTSV originated in the early 18th century from Zhejiang province,and Genotype F was the most primitive one.Henan,Hubei,and Anhui provinces which are located in Dabie Mountain area weremainly epidemic of Genotype A,which emerged relatively late but distributed widely.A total of 37 recombination events were identified,making SFTSV with a high recombination frequency(L segment 5.1%,Msegment 3.6%,S segment 0.8%)among negative-strand segmented RNA viruses.It was identified that 19 reassortant strains belonged to 12 reassortment forms of SFTSV genome containing 6 newly identified forms.The reassortment virus and recombination in tick were both found for the first time.We also found many of genotype-specific mutation sites,7 of which could be considered as potential molecular marker for genotype classification.This study promoted a more comprehensive understanding of the phylogeny and origin,and the genetic diversity of SFTSV,and it could help the studies of other newly discovered tick-borne bunyavirus as reference data and research ideas. | Aqian Li Lin Liu Wei Wu Yang Liu Xiaoxia Huang Chuan Li Di Liu Jiandong Li Shiwen Wang Dexin Li Mifang Liang | 2021 | Biosafety and Health2021，3，2： | 4 |
| 4 | SNX11 Identified as an Essential Host Factor for SFTS Virus Infection by CRISPR Knockout Screening显示文摘Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in humans.The molecular mechanisms and host cellular factors required for SFTSV infection remain uncharacterized.Using a genome-wide CRISPR-based screening strategy,we identified a host cellular protein,sorting nexin 11(SNX11)which is involved in the intracellular endosomal trafficking pathway,as an essential cell factor for SFTSV infection.An SNX11-KO HeLa cell line was established,and SFTSV replication was significantly reduced.The glycoproteins of SFTSV were detected and remained in later endosomal compartments but were not detectable in the endoplasmic reticulum(ER)or Golgi apparatus.pH values in the endosomal compartments of the SNX11-KO cells increased compared with the pH of normal HeLa cells,and lysosomal-associated membrane protein 1(LAMP1)expression was significantly elevated in the SNX11-KO cells.Overall,these results indicated that penetration of SFTSV from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking SNX11.Our study for the first time provides insight into the important role of the SNX11 as an essential host factor in the intracellular trafficking and penetrating process of SFTSV infection via potential regulation of viral protein sorting,membrane fusion,and other endocytic machinery. | Tiezhu Liu Jiajia Li Yang Liu Yuanyuan Qu Aqian Li Chuan Li Quanfu Zhang Wei Wu Jiandong Li Yan Liu Dexin Li Shiwen Wang Mifang Liang | 2019 | Virologica Sinica2019，34，5： | 3 |
| 5 | Antibody Cocktail Exhibits Broad Neutralization Activity Against SARS-CoV-2 and SARS-CoV-2 Variants显示文摘Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic antibodies.In this study,12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries.Of them,two RBD-binding antibodies(F61 and H121)showed high-affinity neutralization against SARS-Co V-2,whereas three S2-target antibodies failed to neutralize SARS-Co V-2.Following structure analysis,F61 identified a linear epitope located in residues G446–S494,which overlapped with angiotensinconverting enzyme 2(ACE2)binding sites,while H121 recognized a conformational epitope located on the side face of RBD,outside from ACE2 binding domain.Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-Co V-2.Importantly,these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351,and reacted with mutations of N501 Y,E484 K,and L452 R,indicated that it may also neutralize the recent India endemic strain B.1.617.The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants,which mitigated the risk of viral escape.Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-Co V-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-Co V-2 variants. | Yuanyuan Qu Xueyan Zhang Meiyu Wang Lina Sun Yongzhong Jiang Cheng Li Wei Wu Zhen Chen Qiangling Yin Xiaolin Jiang Yang Liu Chuan Li Jiandong Li Tianlei Ying Dexin Li Faxian Zhan Youchun Wang Wuxiang Guan Shiwen Wang Mifang Liang | 2021 | Virologica Sinica2021，36，5： | 3 |
| 6 | Development of a reverse transcription quantitative polymerase chain reaction-based assay for broad coverage detection of African and Asian Zika virus lineages显示文摘The Zika virus(ZIKV) is an arbovirus that has spread rapidly worldwide within recent times. There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome(GBS) and microcephaly in humans. The ZIKV is genetically diverse and can be separated into Asian and African lineages. A rapid, sensitive, and specific assay is needed for the detection of ZIKV across various pandemic regions. So far, the available primers and probes do not cover the genetic diversity and geographic distribution of all ZIKV strains. To this end, we have developed a one-step quantitative reverse transcription polymerase chain reaction(qRT-PCR) assay based on conserved sequences in the ZIKV envelope(E) gene. The detection limit of the assay was determined to be five RNA transcript copies and 2.94 × 10^(–3) 50% tissue culture infectious doses(TCID50) of live ZIKV per reaction. The assay was highly specific and able to detect five different ZIKV strains covering the Asian and African lineages without nonspecific amplification, when tested against other flaviviruses. The assay was also successful in testing for ZIKV in clinical samples. Our assay represents an improvement over the current methods available for the detection ZIKV and would be valuable as a diagnostic tool in various pandemic regions. | Yang Yang Gary Wong Baoguo Ye Shihua Li Shanqin Li Haixia Zheng Qiang Wang Mifang Liang George F Gao Lei Liu Yingxia Liu Yuhai Bi | 2017 | Virologica Sinica2017，32，3： | 3 |
| 7 | Serological Investigation of Laboratory-Confirmed and Suspected Ebola Virus Disease Patients During the Late Phase of the Ebola Outbreak in Sierra Leone显示文摘This study aimed to investigate the serological characteristics of Ebola virus(EBOV) infection during the late phase of the Ebola outbreak in Sierra Leone. In total, 877 blood samples from 694 suspected Ebola virus disease(EVD) cases assessed from March to December 2015, were analyzed via real-time reverse transcription polymerase chain reaction(RT-PCR) for viral RNA and enzyme-linked immunosorbent assay(ELISA) and Luminex to detect antibodies against EBOV. Viral load and EBOV-specific IgM/IgG titers displayed a declining trend during March to December 2015. Viral RNA load decreased rapidly at earlier stages after disease onset, while EBOV-specific IgM and IgG still persisted in 58.1%(18/31) and 93.5%(29/31) of the confirmed EVD patients and in 3.8%(25/663) and 17.8%(118/663) of the RNA-negative suspected patients in the later phase, respectively. Dynamic analysis of longitudinally collected samples from eight EVD patients revealed typically reversed trends of declining viral load and increasing IgM and/or IgG titers in response to the EBOV infection.The present results indicate that certain populations of Sierra Leone developed immunity to an EBOV infection in the late phase of the outbreak, providing novel insights into the risk assessment of EBOV infections among human populations. | Yang Liu YuLan Sun Wei Wu AQian Li XianDa Yang Shuo Zhang Chuan Li QiuDong Su ShaoJian Cai DaPeng Sun HaiYang Hu Zhe Zhang XiuXu Yang Idrissa Kamara Sheku Koroma Gerald Bangura Alie Tia Abdul Kamara Matt Lebby Brima Kargbo Jiandong Li Shiwen Wang XiaoPing Dong YueLong Shu WenBo Xu George F. Gao GuiZhen Wu DeXin Li William J. Liu MiFang Liang | 2018 | Virologica Sinica2018，33，4： | 2 |
| 8 | Structure of Severe Fever with Thromboeytopenia Syndrome Virus Nucleocapsid protein in Complex with Suramin Reveals Therapeutic Potentials显示文摘 | Lianying Jiao Songying Ouyang Mifang Liang | 2014 | J Virol Aprilm2014，88，73： | 1 |
| 9 | Early diagnosis of novel SFTS bunyavirus infection by quantitative real-time RT-PCR assay显示文摘 | Yulan Sun Mifang Liang Jing Qu Cong Jin QuanFu Zhang Jiandong Li Xiaolin Jiang Qin Wang Jing Lu Wen Gu Shuo Zhang Chuan Li XianJun Wang Faxian Zhan Wenqing Yao Zhenqiang Bi Shiwen Wang Dexin Li | 2011 | Journal of Clinical Virology2011，，1： | 1 |
| 10 | Rift Valley Fever Virus and Yellow Fever Virus in Urine: A Potential Source of Infection显示文摘Dear Editor,In recent years,the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased.Diseases that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health(Weaver et al.2018).Yellow fever virus(YFV,family Flaviviridae,genus Flavivirus)is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years(Domingo et al.2018). | Meng Li Beibei Wang Liqiang Li Gary Wong Yingxia Liu Jinmin Ma Jiandong Li Hongzhou Lu Mifang Liang Ang Li Xiuqing Zhang Yuhai Bi Hui Zeng | 2019 | Virologica Sinica2019，34，3： | 1 |
| 11 | Antigenic and molecular characterization of hantavirus isolates from China显示文摘 | Mifang Lang Li DX Xiao SY | 1994 | Virus Research1994，31，： | 1 |
| 12 | Generation and characterization of neutralizing human recombinant antibodies against antigenic site II of rabies virus glycoprotein显示文摘 | Lina Sun Zhe Chen Li Yu Jingshuang Wei Chuan Li Jing Jin Xinxin Shen Xinjun Lv Qing Tang Dexin Li Mifang Liang | 2012 | Applied Microbiology and Biotechnology2012，，2： | 1 |
| 13 | Lack of evolutionary changes identified in SARS-CoV-2 for the re-emerging outbreak of COVID-19 in Beijing,China显示文摘Although significant achievements have shown that the coronavirus disease 2019(COVID‐19)resurgence in Beijing,China,was initiated by contaminated frozen products and transported via cold chain transportation,international travelers with asymptomatic symptoms or false‐negative nucleic acid may have another possible transmission mode that spread the virus to Beijing.One of the key differences between these two assumptions was whether the virus actively replicated since,so far,no reports showed viruses could stop evolution in alive hosts.We studied severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)sequences in this outbreak by a modified leaf‐dating method with the Bayes factor.The numbers of single nucleotide variants(SNVs)found in SARS‐CoV‐2 sequences were significantly lower than those called from B.1.1 records collected at the matching time worldwide(P=0.047).In addition,results of the leaf‐dating method showed ages of viruses sampled from this outbreak were earlier than their recorded dates of collection(Bayes factors>10),while control sequences(selected randomly with ten replicates)showed no differences in their collection dates(Bayes factors<10).Our results which indicated that the re‐emergence of SARS‐CoV‐2 in Beijing in June 2020 was caused by a virus that exhibited a lack of evolutionary changes compared to viruses collected at the corresponding time,provided evolutionary evidence to the contaminated imported frozen food should be responsible for the reappearance of COVID‐19 cases in Beijing.The method developed here might also be helpful to provide the very first clues for potential sources of COVID‐19 cases in the future. | Yang Li Yunjun Zhang Mifang Liang Yi Zhang Xuejun Maa Yong Zhang Xiaohua Zhou | 2022 | Biosafety and Health2022，4，1： | 1 |
| 14 | Fever with thrombocytopenia associated with a novel bunyavirus in China 显示文摘 | Yu Xuejie Liang Mifang Zhang Shouyin | 2011 | N EnglJ Med2011，364，16： | 1 |
| 15 | Antigenic and charactertzation of hantavirus isolates from China 显示文摘 | Mifang L Dexin L Shuyuan X | 1994 | Virus Res1994，31，： | 1 |
| 16 | Intra-host Ebola viral adaption during human infection显示文摘The onsite next generation sequencing(NGS)of Ebola virus(EBOV)genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin,transmission,and evolution of this virus.Herein,we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015,during the late phase of the outbreak.The surviving EBOV patients had a recovery process characterized by decreasing viremia,fever,and biochemical parameters.EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection,including the previously described short stretches of 13 serial TNC mutations.Remarkably,within individual patients,samples collected during the early phase of infection possessed Ts at these nucleotide sites,whereas they were replaced by Cs in samples collected in the later phase,suggesting that these short stretches of TNC mutations could emerge independently.In addition,up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently.Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions. | William JLiu Weifeng Shi Wuyang Zhu Cong Jin Shumei Zou Ji Wang Yuehua Ke Xiaofeng Li Mi Liu Tao Hu Hang Fan Yigang Tong Xiang Zhao Wenbin Chen Yuhui Zhao Di Liu Gary Wong Chengchao Chen Chunyu Geng Weiwei Xie Hui Jiang Idrissa Laybor Kamara Abdul Kamara Matt Lebby Brima Kargbo Xiangguo Qiu Yu Wang Xiaofeng Liang Mifang Liang Xiaoping Dong Guizhen Wu George F.Gao Yuelong Shu | 2019 | Biosafety and Health2019，1，1： | 1 |
| 17 | Bacterial expression of neutralizing mouse monoclonal antibody Fab fragments to Hantaan virus显示文摘 | Mifang LN Yong-Kyu CH Schmaiohn C | 1996 | Virol1996，217，1： | 1 |
| 18 | Fever with Throm- bocytopenia Associated with a Novel Bunyavirus in China 显示文摘 | Yu Xuejie Liang Mifang Zhang Shouyin | 2011 | N Engl J Med2011，364，16： | 1 |
| 19 | Antigenic and charactertzation of hantavirus isolates from China显示文摘 | Mifang L Dexin L Shuyuan X | 1994 | Virus Res1994，31，： | 1 |
| 20 | Fever with thrombocytopenia associated with a novel bunyavirus in China 显示文摘 | Yu Xuejie Liang Mifang Zhang Shouyin | 2011 | N Engl J Med2011，364，16： | 1 |
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