Study on Biologic Activity for Membrane of Normal Bone Marrow Cells with Infection of Epidemic Hemorrhagic Fever Virus

Using DPH fluorescence probe, the membrane of normal bone marrow cells with infection of epidemic hemorrhagic fever virus (EHFV) was labeled. The membrane lipid fluidity was obviously decreased from the membrane lipid fluorescence polarization. The membrane lipid fluidity of lympho- cyte, monocyte and neutrophilic granulocyte was dynamically observed. After culturing the cells for 1, 6, 24 and 72 h, it was found that all the membrane lipid fluidity of the infected cells was de- creased obviously with the longer the culturing time, the more obvious it. Compared with the normal control groups, there was a significant difference statistically (P<0. 05-0. 01). It was suggested that the decrease of the membrane lipid fluidity of normal bone marrow cell with infection of EHFV had correlation with the degree of virus invading and cellfunction injury.

Transcriptome profiling highlights regulated biological processes and type III interferon antiviral responses upon Crimean-Congo hemorrhagic fever virus infection

Crimean-Congo hemorrhagic fever virus(CCHFV)is a biosafety level-4(BSL-4)pathogen that causes Crimean-Congo hemorrhagic fever(CCHF)characterized by hemorrhagic manifestation,multiple organ failure and high mortality rate,posing great threat to public health.Despite the recently increasing research efforts on CCHFV,host cell responses associated with CCHFV infection remain to be further characterized.Here,to better understand the cellular response to CCHFV infection,we performed a transcriptomic analysis in human kidney HEK293 cells by high-throughput RNA sequencing(RNA-seq)technology.In total,496 differentially expressed genes(DEGs),including 361 up-regulated and 135 down-regulated genes,were identified in CCHFV-infected cells.These regulated genes were mainly involved in host processes including defense response to virus,response to stress,regulation of viral process,immune response,metabolism,stimulus,apoptosis and protein catabolic process.Therein,a significant up-regulation of type III interferon(IFN)signaling pathway as well as endoplasmic reticulum(ER)stress response was especially remarkable.Subsequently,representative DEGs from these processes were well validated by RT-qPCR,confirming the RNA-seq results and the typical regulation of IFN responses and ER stress by CCHFV.Furthermore,we demonstrate that not only type I but also type III IFNs(even at low dosages)have substantial anti-CCHFV activities.Collectively,the data may provide new and comprehensive insights into the virus-host interactions and particularly highlights the potential role of type III IFNs in restricting CCHFV,which may help inform further mechanistic delineation of the viral infection and development of anti-CCHFV strategies.

Crimean-Congo hemorrhagic fever virus in Central,Eastern,and South-eastern Asia

Crimean-Congo hemorrhagic fever(CCHF),caused by Crimean-Congo hemorrhagic fever virus(CCHFV),is endemic in Africa,Asia,and Europe,but CCHF epidemiology and epizootiology is only rudimentarily defined for most regions.Here we summarize what is known about CCHF in Central,Eastern,and South-eastern Asia.Searching multiple international and country-specific databases using a One Health approach,we defined disease risk and burden through identification of CCHF cases,anti-CCHFV antibody prevalence,and CCHFV isolation from vector ticks.We identified 2313 CCHF cases that occurred in 1944–2021 in the three examined regions.Central Asian countries reported the majority of cases(2,026).In Eastern Asia,China was the only country that reported CCHF cases(287).In South-eastern Asia,no cases were reported.Next,we leveraged our previously established classification scheme to assign countries to five CCHF evidence levels.Six countries(China,Kazakhstan,Kyrgyzstan,Tajikistan,Turkmenistan,and Uzbekistan)were assigned to level 1 or level 2 based on CCHF case reports and the maturity of the countries’surveillance systems.Two countries(Mongolia and Myanmar)were assigned to level 3 due to evidence of CCHFV circulation in the absence of reported CCHF cases.Thirteen countries in Eastern and South-eastern Asia were categorized in levels 4 and 5 based on prevalence of CCHFV vector ticks.Collectively,this paper describes the past and present status of CCHF reporting to inform international and local public-health agencies to strengthen or establish CCHFV surveillance systems and address shortcomings.

Cryo-EM structure of glycoprotein C from Crimean-Congo hemorrhagic fever virus

Crimean-Congo hemorrhagic fever virus(CCHFV)is a causative agent of serious hemorrhagic diseases in humans with high mortality rates.CCHFV glycoprotein Gc plays critical roles in mediating virus-host membrane fusion and has been studied extensively as an immunogen.However,the molecular mechanisms involved in membrane fusion and Gc-specific antibody-antigen interactions remain unresolved largely because structural information of this glycoprotein is missing.We designed a trimeric protein including most of the ectodomain region of Gc from the prototype CCHFV strain,Ib Ar10200,which enabled the cryo-electron microscopy structure to be solved at a resolution of 2.8Å.The structure confirms that CCHFV Gc is a class Ⅱ fusion protein.Unexpectedly,structural comparisons with other solved Gc trimers in the postfusion conformation revealed that CCHFV Gc adopted hybrid architectural features of the fusion loops from hantaviruses and domain Ⅲ from phenuiviruses,suggesting a complex evolutionary pathway among these bunyaviruses.Antigenic sites on CCHFV Gc that protective neutralizing antibodies target were mapped onto the CCHFV Gc structure,providing valuable information that improved our understanding of potential neutralization mechanisms of various antibodies.

Crimean-Congo hemorrhagic fever from the immunopathogenesis, clinical, diagnostic, and therapeutic perspective: A scoping review

Crimean-Congo hemorrhagic fever virus(CCHFV) is responsible for widespread tick-borne zoonotic viral disease CCHF in African, Middle Eastern, Asian, and European countries. CCHFV can be spread to humans through tick bites or contact with infected animals or humans, and it often progresses from asymptomatic to severe/lethal illness, with fatality rates ranging from 10% to 40% in humans. Today, CCHF is growing into a significant public health concern due to its very high prevalence, severity of the condition, and lack of available vaccines and specific treatments. Recent research has been drawn towards a more accurate study of CCHFV characteristics, including the structure, genetic diversity, mechanisms involved in pathogenesis and immunopathogenesis, and clinical features. In addition, the use of animal models(mouse and non-human primates) and advanced diagnostic tools in recent years has resulted in a significant advance in CCHF related studies. In this context, we summarized the latest findings about CCHF research, its health complications, animal models, current diagnosis, vaccination, and CCHF treatments, and therapeutic strategies. Furthermore, we discussed existing deficiencies and problems in CCHFV analysis, as well as areas that still need to yield conclusive answers.

Prevalence of Crimean-Congo hemorrhagic fever in Pakistan and its new research progress

Crimean-Congo hemorrhagic fever is a deadly and life-threatening viral sickness spreading throughout the world with high mortality rate of 10%–40%.The causative agents are ticks which show diversity in their strains and thus it is difficult to make vaccine,however some strains are conserved which is the positive point in vaccines development.From 2012 to 2015,a total of 161 cases were confirmed for Crimean-Congo hemorrhagic fever virus in Pakistan.And from 2012 to July 2014,45 deaths were reported in the country.It is spreading sporadically in Pakistan.Mapping of endemic areas and cross-border veterinary surveillance should be developed in high risk areas and workshops should be arranged to increase public awareness about the disease.Control measures must be taken to avoid spreading of the disease to new areas.

Mapping the viruses belonging to the order Bunyavirales in China

Background:Viral pathogens belonging to the orderBunyavirales pose a continuous background threat to global health,but the fact remains that they are usually neglected and their distribution is still ambiguously known.We aim to map the geographical distribution ofBunyavirales viruses and assess the environmental suitability and transmission risk of majorBunyavirales viruses in China.Methods:We assembled data on allBunyavirales viruses detected in humans,animals and vectors from multiple sources,to update distribution maps of them across China.In addition,we predicted environmental suitability at the 10 km×10 km pixel level by applying boosted regression tree models for two importantBunyavirales viruses,including Crimean-Congo hemorrhagic fever virus(CCHFV)and Rift Valley fever virus(RVFV).Based on model-projected risks and air travel volume,the imported risk of RVFV was also estimated from its endemic areas to the cities in China.Results:Here we mapped all 89 species ofBunyavirales viruses in China from January 1951 to June 2021.Nineteen viruses were shown to infect humans,including ten species first reported as human infections.A total of 447,848 cases infected withBunyavirales viruses were reported,and hantaviruses,Dabie bandavirus and Crimean-Congo hemorrhagic fever virus(CCHFV)had the severest disease burden.Model-predicted maps showed that Xinjiang and southwestern Yunnan had the highest environmental suitability for CCHFV occurrence,mainly related toHyalomma asiaticum presence,while southern China had the highest environmental suitability for Rift Valley fever virus(RVFV)transmission all year round,mainly driven by livestock density,mean precipitation in the previous month.We further identified three cities including Guangzhou,Beijing and Shanghai,with the highest imported risk of RVFV potentially from Egypt,South Africa,Saudi Arabia and Kenya.Conclusions:A variety ofBunyavirales viruses are widely distributed in China,and the two major neglectedBunyavirales viruses including CCHFV and RVFV,both have the potential for outbreaks in local areas of China.Our study can help to promote the understanding of risk distribution and disease burden ofBunyavirales viruses in China,and the risk maps of CCHFV and RVFV occurrence are crucial to the targeted surveillance and control,especially in seasons and locations at high risk.