Establishment and application of a surrogate model for human Ebola virus disease in BSL-2 laboratory

The Ebola virus(EBOV)is a member of the Orthoebolavirus genus,Filoviridae family,which causes severe hemorrhagic diseases in humans and non-human primates(NHPs),with a case fatality rate of up to 90%.The development of countermeasures against EBOV has been hindered by the lack of ideal animal models,as EBOV requires handling in biosafety level(BSL)-4 facilities.Therefore,accessible and convenient animal models are urgently needed to promote prophylactic and therapeutic approaches against EBOV.In this study,a recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein(VSV-EBOV/GP)was constructed and applied as a surrogate virus,establishing a lethal infection in hamsters.Following infection with VSV-EBOV/GP,3-week-old female Syrian hamsters exhibited disease signs such as weight loss,multi-organ failure,severe uveitis,high viral loads,and developed severe systemic diseases similar to those observed in human EBOV patients.All animals succumbed at 2–3 days post-infection(dpi).Histopathological changes indicated that VSV-EBOV/GP targeted liver cells,suggesting that the tissue tropism of VSV-EBOV/GP was comparable to wild-type EBOV(WT EBOV).Notably,the pathogenicity of the VSV-EBOV/GP was found to be species-specific,age-related,gender-associated,and challenge route-dependent.Subsequently,equine anti-EBOV immunoglobulins and a subunit vaccine were validated using this model.Overall,this surrogate model represents a safe,effective,and economical tool for rapid preclinical evaluation of medical countermeasures against EBOV under BSL-2 conditions,which would accelerate technological advances and breakthroughs in confronting Ebola virus disease.

Oncolytic viruses:A novel treatment strategy for breast cancer

Breast cancer,an unceasingly occurring neoplasm,is one of the major determinants of mortality in women.Several ineffective attempts have been pursued using with conventional therapies against breast cancer.Resistance to existing therapies and their respective debilitating adverse effects have led research toward a new era of cancer treatment using viruses.Virotherapy constitutes a developing treatment modality with multiple mechanisms of therapeutic activity in which the viruses can be directly oncolyticand can express transgenes or induce host immune response against tumor cells.Several different DNA-and RNA-containing viruses have been considered for virotherapy of breast cancer including adenovirus,herpes virus,vaccinia,reovirus,Newcastle Disease virus,measles virus and vesicular stomatitis virus.This review aims to summarize the viro-therapeutical agents against breast malignancies.Key Scientific Concepts of Review:In this review paper,we proposed a new strategy to virus's combinatorial treatments using several kinds of transgenes and drugs.These recombinant viruses have provided evidence of treatment efficacy against human breast cancer.

FOLR1-induced folate deficiency reduces viral replication via modulating APOBEC3 family expression

Folate receptor alpha(FOLR1)is vital for cells ingesting folate(FA).FA plays an indispensable role in cell pro-liferation and survival.However,it is not clear whether the axis of FOLR1/FA has a similar function in viral replication.In this study,we used vesicular stomatitis virus(VSV)to investigate the relationship between FOLR1-mediated FA deficiency and viral replication,as well as the underlying mechanisms.We discovered that FOLR1 upregulation led to the deficiency of FA in HeLa cells and mice.Meanwhile,VSV replication was notably sup-pressed by FOLR1 overexpression,and this antiviral activity was related to FA deficiency.Mechanistically,FA deficiency mainly upregulated apolipoprotein B mRNA editing enzyme catalytic subunit 3B(APOBEC3B)expression,which suppressed VSV replication in vitro and in vivo.In addition,methotrexate(MTX),an FA metabolism inhibitor,effectively inhibited VSV replication by enhancing the expression of APOBEC3B in vitro and in vivo.Overall,our present study provided a new perspective for the role of FA metabolism in viral infections and highlights the potential of MTX as a broad-spectrum antiviral agent against RNA viruses.

Immunogenicity of a recombinant VSV-Vectored SARS-CoV vaccine induced robust immunity in rhesus monkeys after single-dose immunization

Severe acute respiratory syndrome(SARS)is a highly contagious zoonotic disease caused by SARS coronavirus(SARS-Co V).Since its outbreak in Guangdong Province of China in 2002,SARS has caused 8096 infections and774 deaths by December 31st,2003.Although there have been no more SARS cases reported in human populations since 2004,the recent emergence of a novel coronavirus disease(COVID-19)indicates the potential of the recurrence of SARS and other coronavirus disease among humans.Thus,developing a rapid response SARS vaccine to provide protection for human populations is still needed.Spike(S)protein of SARS-Co V can induce neutralizing antibodies,which is a pivotal immunogenic antigen for vaccine development.Here we constructed a recombinant chimeric vesicular stomatitis virus(VSV)VSVΔG-SARS,in which the glycoprotein(G)gene is replaced with the SARS-Co V S gene.VSVΔG-SARS maintains the bullet-like shape of the native VSV,with the heterogeneous S protein incorporated into its surface instead of G protein.The results of safety trials revealed that VSVΔG-SARS is safe and effective in mice at a dose of 1×10^(6)TCID_(50).More importantly,only a single-dose immunization of 2×10^(7)TCID_(50)can provide high-level neutralizing antibodies and robust T cell responses to non-human primate animal models.Thus,our data indicate that VSVΔG-SARS can be used as a rapid response vaccine candidate.Our study on the recombinant VSV-vectored SARS-Co V vaccines can accumulate experience and provide a foundation for the new coronavirus disease in the future.