title: Pseudoinfectious Venezuelan equine encephalitis virus: a new means of alphavirus attenuation.
abstract: Venezuelan equine encephalitis virus (VEEV) is a reemerging virus that causes a severe and often fatal disease in equids and humans. In spite of a continuous public health threat, to date, no vaccines or antiviral drugs have been developed for human use. Experimental vaccines demonstrate either poor efficiency or severe adverse effects. In this study, we developed a new strategy of alphavirus modification aimed at making these viruses capable of replication and efficient induction of the immune response without causing a progressive infection, which might lead to disease development. To achieve this, we developed a pseudoinfectious virus (PIV) version of VEEV. VEE PIV mimics natural viral infection in that it efficiently replicates its genome, expresses all of the viral structural proteins, and releases viral particles at levels similar to those found in wild-type VEEV-infected cells. However, the mutations introduced into the capsid protein make this protein almost incapable of packaging the PIV genome, and most of the released virions lack genetic material and do not produce a spreading infection. Thus, VEE PIV mimics viral infection in terms of antigen production but is safer due to its inability to incorporate the viral genome into released virions. These genome-free virions are referred to as virus-like particles (VLPs). Importantly, the capsid-specific mutations introduced make the PIV a very strong inducer of the innate immune response and add self-adjuvant characteristics to the designed virus. This unique strategy of virus modification can be applied for vaccine development against other alphaviruses.
authors.affiliation: Department of Microbiology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Atasheva
authors.forename: Dal Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Maryna
authors.initials: M
authors.lastname: Akhrymuk
authors.forename: David G
authors.initials: DG
authors.lastname: Morgan
authors.forename: Elena I
authors.initials: EI
authors.lastname: Frolova
authors.forename: Ilya
authors.initials: I
authors.lastname: Frolov
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000235:genetics* / Q000276:immunology; D019065:Virus Assembly; D057074:Virus Release; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins; D014613:Vaccines, Attenuated; D058425:Vaccines, Virus-Like Particle