Activation of IP10/CXCR3 Signaling is Highly Coincidental with PrP^(Sc)Deposition in the Brains of Scrapie-Infected Mice

Objective To analyze the relationship between Chemokine IP10 and its receptor CXCR3 during prion infection.Methods We investigated the increases in IP10 signals,primarily localized in neurons within the brains of scrapie-infected mice,using western blotting,ELISA,co-immunoprecipitation,immunohistochemistry,immunofluorescence assays,and RT-PCR.Results Both CXCR3 levels and activation were significantly higher in the brains of scrapie-infected mice and prion-infected SMB-S15 cells.Enhanced CXCR3 expression was predominantly observed in neurons and activated microglia.Morphological colocalization of PrPC/PrPSc with IP10/CXCR3 was observed in scrapie-infected mouse brains using immunohistochemistry and immunofluorescence.immunohistochemistry(IHC)analysis of whole brain sections further revealed increased accumulation of IP10/CXCR3 specifically in brain regions with higher levels of PrPSc deposits.Co-immunoprecipitation and biomolecular interaction assays revealed the molecular interactions between PrP and IP10/CXCR3.Notably,a significantly larger amount of IP10 accumulated within prion-infected SMB-S15 cells than in the normal partner cell line,SMB-PS.Importantly,resveratrol treatment effectively suppressed prion replication in SMB-S15 cells,thereby restoring the accumulation and secretion pattern of cellular IP10 similar to that observed in SMB-PS cells.Conclusion Our data demonstrate that the activation of IP10/CXCR3 signaling in prion-infected brain tissues coincides with PrPSc deposition.Modulation of IP10/CXCR3 signaling in the brain represents a potential therapeutic target for mitigating the progression of prion diseases.

Seroprevalence of neutralizing antibodies against HFMD associated enteroviruses among healthy individuals in Shanghai,China,2022

Dear Editor,Hand,foot and mouth disease(HFMD)is one of the most common infectious diseases,particularly in the Asia-Pacific region.In the past two decades,HFMD rises to prominence for its heavy burden,with over one million cases reported annually.Before 2013,enterovirus A71(EV-A71)and Coxsackievirus A16(CVA16)were the main pathogens leading to HFMD in the mainland of China(Yang et al.,2017).In recent years,non-EV-A71-non-CVA16 other enteroviruses,such as Coxsackievirus A6(CVA6),Coxsackievirus A10(CVA10)and Coxsackievirus A4(CVA4),were frequently reported and replaced EV-A71 and CVA16 becoming the major causative agents of HFMD(Zhou et al.,2021;Wang et al.,2022).

Genomic surveillance of coxsackievirus A10 reveals genetic features and recent appearance of genogroup D in Shanghai,China,2016–2020

Coxsackievirus A10(CVA10)is one of the major causative agents of hand,foot and mouth disease(HFMD).To investigate the epidemiological characteristics as well as genetic features of CVA10 currently circulating in Shanghai,China,we collected a total of 9,952 sporadic HFMD cases from January 2016 to December 2020.In the past five years,CVA10 was the fourth prevalent causatives associated with HFMD in Shanghai and the overall positive rate was 2.78%.The annual distribution experienced significant fluctuations over the past five years.In addition to entire VP1 sequencing,complete genome sequencing and recombination analysis of CVA10 isolates in Shanghai were further performed.A total of 64 near complete genomes and 11 entire VP1 sequences in this study combined with reference sequences publicly available were integrated into phylogenetic analysis.The CVA10sequences in this study mainly belonged to genogroup C and presented 91%-100%nucleotide identity with other Chinese isolates based on VP1 region.For the first time,our study reported the appearance of CVA10 genogroup D in Chinese mainland,which had led to large-scale outbreaks in Europe previously.The recombination analysis showed the recombination break point located between 5,100 nt and 6,700 nt,which suggesting intertypic recombination with CVA16 genogroup D.To conclusion,CVA10 genogroup C was the predominant genogroup in Shanghai during 2016-2020.CVA10 recombinant genogroup D was firstly reported in circulating in Chinese mainland.Continuous surveillance is needed to better understand the evolution relationships and transmission pathways of CVA10 to help to guide disease control and prevention.

Eleven COVID-19 Outbreaks with Local Transmissions Caused by the Imported SARS-CoV-2 Delta VOC-China,July-August,2021

Starting from December 2019,Wuhan,China,encountered the first outbreak of coronavirus disease 2019(COVID-19)(1-2).The epidemic was successfully suppressed by strict containment so that the number of infected people was reduced to 0 on April 8,2020(3–4).After that,China experienced roughly 3 dozen outbreaks with local transmission caused by imported severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).

Epidemiology and genetic characteristics of coxsackievirus A16 associated with hand-foot-and-mouth disease in Yantai city,China in 2018-2021

In 2008,China launched a national surveillance system for hand‐foot‐and‐mouth disease(HFMD).Several million cases of HFMD are reported every year,coxsackievirus A16(CVA16)was the leading cause of HFMD epidemic in Yantai city,China in recent years,but the information of epidemiology and molecular characterization of CVA16 in Yantai is limited.The aim of this study is to investigate the epidemiological characteristics and pathogenic spectrum of HFMD,and most importantly,the molecular characterization of CVA16 in Yantai from 2018 to 2021.A total of 2,000 clinical samples were collected in Yantai city from 2018 to 2021 and the enterovirus typing was performed using real‐time reverse transcriptase–polymerase chain reaction(qRT‐PCR).VP1 coding regions of 41 CVA16 isolates were amplified and Sanger sequenced,and phylogenetic analysis was performed.During the study period,HFMD became prevalent from May to August each year.It peaked in June and declined in September.The incidence was highest in children aged 1 to 5 years,while more common in males than females.1,617 out of 2,000 clinical collection of samples were tested positive for enterovirus.Among them,614 were identified as CVA16,45 were enterovirus A71(EV A17),and 958 were other enterovirus serotypes.All 41 CVA16 strains belonged to the Bla and B1b genotypes.Homology analysis showed that 41 CVA16 isolates shared 83.2%–100%nucleotide and 93.7%–100%amino acid similarity among themselves.The results of this study update molecular epidemiology of CVA16 and provide a reference for HFMD prevention and control.

New Simian Enterovirus 19(EV-A122) Strains in China Reveal Large-Scale Inter-Serotype Recombination between Simian EV-As

Dear Editor,The genus Enterovirus(EV),belonging to the family Picornaviridae,order Picornavirales,comprises 15 species:Enterovirus A–L and rhinovirus A–C(Zell et al.2017).Enterovirus A(EV-A)has 25 serotypes,including several pathogens,such as EV-A71,coxsackievirus A16(CV-A16),and CV-A6 that infect humans,as well as four serotypes(EV-A122,123,124,and 125)isolated from simians(Zell et al.2017).EV genomes share a similar structure with a length of 7.5 kb,and two open reading frames(ORFs)flanked by 5′-and 3′-untranslated regions(UTRs)in some EVs(Oberste et al.2013b;Zell et al.2017;Guo et al.2019;Lulla et al.2019).