Efficient, trans-complementing packaging systems for chimeric, pseudoinfectious dengue 2/yellow fever viruses.
In our previous studies, we have stated to build a new strategy for developing defective, pseudoinfectious flaviviruses (PIVs) and applying them as a new type of vaccine candidates. PIVs combined the efficiency of live vaccines with the safety of inactivated or subunit vaccines. The results of the present work demonstrate further development of chimeric PIVs encoding dengue virus 2 (DEN2V) glycoproteins and yellow fever virus (YFV)-derived replicative machinery as potential vaccine candidates. The newly designed PIVs have synergistically functioning mutations in the prM and NS2A proteins, which abolish processing of the latter proteins and make the defective viruses capable of producing either only noninfectious, immature and/or subviral DEN2V particles. The PIV genomes can be packaged to high titers into infectious virions in vitro using the NS1-deficient YFV helper RNAs, and both PIVs and helpers can then be passaged as two-component genome viruses at an escalating scale.
Department of Microbiology, BBRB 373/Box 3, University of Alabama, Birmingham, AL 35294-2170, USA.
Alexandr V
AV
Shustov
Ilya
I
Frolov
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003673:Defective Viruses / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D003716:Dengue Virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D005816:Genetic Complementation Test; D016679:Genome, Viral; D049452:Green Fluorescent Proteins / Q000235:genetics; D006378:Helper Viruses / Q000235:genetics / Q000502:physiology; D016296:Mutagenesis; D014614:Vaccines, Synthetic / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D019065:Virus Assembly / Q000235:genetics* / Q000502:physiology*; D014779:Virus Replication; D015005:Yellow fever virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*
C079341:NS2A protein, Dengue virus type 2; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; D049452:Green Fluorescent Proteins