A rapid and visual detection method for Crimean-Congo hemorrhagic fever virus by targeting S gene

Crimean-Congo hemorrhagic fever(CCHF)is a zoonotic disease caused by the CCHF virus(CCHFV),which is primarily transmitted by ticks(Lorenzo Juanes et al.2023).It is an emerging disease that occurs sporadically in Africa,Asia,and Europe,with a high morbidity and mortality rate,as high as 30%in humans(Ceylan et al.2013).CCHFV,belonging to genus Nairovirus,family Bunyaviridae,was first identified in the Congo in the 1960s.

Regulation of innate immune responses by rabies virus

Rabies virus(RABV)is an infectious and neurotropic pathogen that causes rabies and infects humans and almost all warm-blooded animals,posing a great threat to people and public safety.It is well known that innate immunity is the critical first line of host defense against viral infection.It monitors the invading pathogens by recognizing the pathogen-associated molecular patterns and danger-associated molecular patterns through pattern-recognition receptors,leading to the production of type I interferons(IFNα/β),inflammatory cytokines,and chemokines,or the activation of autophagy or apoptosis to inhibit virus replication.In the case of RABV,the innate immune response is usually triggered when the skin or muscle is bitten or scratched.However,RABV has evolved many ways to escape or even hijack innate immune response to complete its own replication and eventually invades the central nervous system(CNS).Once RABV reaches the CNS,it cannot be wiped out by the immune system or any drugs.Therefore,a better understanding of the interplay between RABV and innate immu-nity is necessary to develop effective strategies to combat its infection.Here,we review the innate immune responses induced by RABV and illustrate the antagonism mechanisms of RABV to provide new insights for the control of rabies.

Genetically engineered bacterial-like particles induced specific cellular and humoral immunity as effective tick-borne encephalitis virus vaccine

Tick-borne encephalitis(TBE)is a natural focal disease with fatal encephalitis induced by tick-borne encephalitis virus(TBEV),seriously threatening human and public health.Protection of TBE depends on vaccination with inactivated vaccine,which requires high cost and multiple immunizations.Here,we construct genetically engineered bacterial-like particles(BLPs)as an effective TBEV vaccine with simplified immunizations and improved immune efficacy.The TBEV BLPs involve the combination of the gram-positive enhancer matrix from Lactococcus lactis,and TBEV envelope(E)protein expressed by genetically engineered recombinant baculovirus.The prepared TBEV BLPs can effectively stimulate the activation of dendritic cells to present the TBEV E proteins to T and B cells,leading to strong and durable cellular and humoral immune responses in mice.Surprisingly,the serum levels of specific IgG antibodies in mice remain about 10^(6)at 6 months after the secondary immunization.Overall,the TBEV BLPs can be used as a potent vaccine candidate,laying the foundation for developing novel TBEV genetically engineered vaccines.

An inactivated recombinant rabies virus chimerically expressed RBD induces humoral and cellular immunity against SARS-CoV-2 and RABV

Many studies suggest that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can infect various animals and transmit among animals,and even to humans,posing a threat to humans and animals.There is an urgent need to develop inexpensive and efficient animal vaccines to prevent and control coronavirus disease 2019(COVID-19)in animals.Rabies virus(RABV)is another important zoonotic pathogen that infects almost all warmblooded animals and poses a great public health threat.The present study constructed two recombinant chimeric viruses expressing the S1 and RBD proteins of the SARS-CoV-2 Wuhan01 strain based on a reverse genetic system of the RABV SRV9 strain and evaluated their immunogenicity in mice,cats and dogs.The results showed that both inactivated recombinant viruses induced durable neutralizing antibodies against SARS-CoV-2 and RABV and a strong cellular immune response in mice.Notably,inactivated SRV-nCoV-RBD induced earlier antibody production than SRV-nCoV-S1,which was maintained at high levels for longer periods.Inactivated SRV-nCoV-RBD induced neutralizing antibodies against both SARS-CoV-2 and RABV in cats and dogs,with a relatively broadspectrum cross-neutralization capability against the SARS-CoV-2 pseudoviruses including Alpha,Beta,Gamma,Delta,and Omicron,showing potential to be used as a safe bivalent vaccine candidate against COVID-19 and rabies in animals.

Incorporation of Escherichia coli heat-labile enterotoxin B subunit into rabies virus particles enhances its immunogenicity in mice and dogs

Although inactivated vaccines against rabies have the advantage of high safety,effective protection against rabies virus(RABV)infection often requires multiple,high-dose immunization.Incorporating a molecular adjuvant into the viral particles has been found to be a useful strategy to promote the immune effectiveness of inactivated vaccines.In this study,we constructed a recombinant virus,rCVS11-LTB,which chimerically expresses a molecular adjuvant heat-labile enterotoxin B subunit(LTB)protein on the surface of the RABV particles.Immunogenicity in vivo was found to be promoted by rCVS11-LTB through the activation of dendritic cells(DCs).Our results demonstrated that inactivated rCVS11-LTB was able to induce higher levels of virusneutralizing antibodies(VNAs)in both mice and dogs than the parent virus rCVS11,to enhance the cellular immune response and T cell immune memory in mice,and was also able to provide 100%protection in mice from lethal doses of rabies virus,indicating its potential as a safe and effective inactivated rabies vaccine candidate.

A visual assay panel for the identification of monkeypox virus DNA belonging to the clades I and II

Dear Editor,Monkeypox virus(MPXV)is an enveloped double-stranded DNA virus belonging to the family Poxviridae,subfamily Chordopoxvirinae,and genus Orthopoxvirus(Hraib et al.,2022;Gong et al.,2022).MPXV forms Congo Basin clade(clade I)and West African clade(clade II)(Durski et al.,2018).Additionally,clade II consists of two subclades,clade IIa and clade IIb.

一种新型ω-转氨酶的工业适应性选择

尽管ω-转氨酶被认为是手性胺合成中极具工业潜力的生物催化剂,但是由于受限于酶的热不稳定及不利的反应平衡,能直接适用于工业的野生酶极少。为了发现工业适应潜力的新型ω-转氨酶,文中设计了包括底物、序列、克隆、酶活、转化率及酶学的工业适应性选择流程,并对各筛选步骤中存在的问题进行了研究,进而从土壤宏基因组中筛选出了一种来源于柄杆菌属的新型ω-转氨酶ATA-W12,以异丙胺为供体在1mL反应体系中转化了85.84%1-Boc-3-吡咯烷酮(20 mmol/L)和67.42%1-Boc-3-哌啶酮(20 mmol/L)。酶学筛选发现,ATA-W12在40℃孵育168 h活力维持不变;优选反应条件为pH 8.5、40℃;这些特征利于工业用理想氨基供体异丙胺的使用。笔者已采用ATA-W12实现了100g/L光学纯(S)-(+)-1-Boc-3-氨基哌啶的50mL实验室规模制备,为进一步工业化生产打下基础。

Ubiquitination of SARS-CoV-2 ORF7a promotes antagonism of interferon response

Understanding interactions between the host and SARS-CoV-2 is essential for developing effective vaccines and therapeutics.Here,we report that SARS-CoV-2 usurps the host ubiquitin system to polyubiquitinate accessory protein ORF7a at Lys119.The 0RF7a polyubiquitination is primarily formed by K63-linked ubiquitin chains.

Abnormal odd-even staggering behavior around^132Sn studied by density functional theory

In this work,we have performed Skyrme density functional theory(DFT)calculations of nuclei around^132Sn to study whether the abnormal odd-even staggering(OES)behavior of binding energies around N=82 can be reproduced.With the Skyrme forces SLy4 and SkM*,we tested the volume-and surface-type pairing forces and also the intermediate between these two pairing forces,in the Hartree-Fock-Bogoliubov(HFB)approximation with or without the Lipkin-Nogami(LN)approximation or particle number projection after the convergence of HFBLN(PLN).The Universal Nuclear Energy Density Function(UNEDF)parameter sets are also used.The trend of the neutron OES against the neutron number or proton number does not change significantly by tuning the density dependence of the pairing force.Moreover,for the pairing force that is favored more at the nuclear surface,a larger mass OES is obtained,and vice versa.It appears that the combination of volume and surface pairing can give better agreement with the data.In the studies of the OES,a larger ratio of surface to volume pairing might be favored.Additionally,in most cases,the OES given by the HFBLN approximation agrees more closely with the experimental data.We found that both the Skyrme and pairing forces can influence the OES behavior.The mass OES calculated by the UNEDF DFT is explicitly smaller than the experimental one.The UNEDF1 and UNEDF2 forces can reproduce the experimental trend of the abnormal OES around^132Sn.The neutron OES of the tin isotopes given by the SkM*force agrees more closely with the experimental one than that given by the SLy4 force in most cases.Both SLy4 and SkM*DFT have difficulties in reproducing the abnormal OES around^132Sn.Using the PLN method,the systematics of OES are improved for several combinations of Skyrme and pairing forces.

The Application of a Safe Neutralization Assay for Ebola Virus Using Lentivirus-Based Pseudotyped Virus

Dear Editor,Zaire Ebola virus(EBOV)is a negative-sense singlestranded RNA virus that is capable of causing acute hemorrhagic fever with a frightening fatality rate that can reach up to 90%.Due to its high lethality and frequent recurrence,EBOV is a substantial threat to public health.Research about live EBOV is restricted to BSL-4 laboratories;therefore,conventional serological detection methods do not provide a safe way to evaluate neutralizing activity,resulting in a bottleneck in antibody-based detection of viruses such as EBOV.Here,we aim to develop and apply a neutralization assay for EBOV using a generated lentivirus-based pseudotyped EBOV bearing GP on its surface.

Prevention and control of zoonoses at their source:from the Chinese perspective

Zoonoses are a significant public health concern and cause considerable socioeconomic problems globally.The emergence of severe acute respiratory syndrome(SARS),highly pathogenic avian influenza(HPAI),and Ebola virus disease(EVD)has had a significant effect on the national economy and public health in China,and other countries.This review analyzed zoonotic disease issues faced by China,and the main factors contributing to the risk of zoonotic disease.The Chinese government has devised new strategies and has taken measures to deal with the challenges of these diseases,and the prevention and control of zoonoses at their source.A strategy that is suited to China’s national conditions,is proposed.