title: Reverse genetics of Mononegavirales: How they work, new vaccines, and new cancer therapeutics.
abstract: The order Mononegavirales includes five families: Bornaviridae, Filoviridae, Nyamaviridae, Paramyxoviridae, and Rhabdoviridae. The genome of these viruses is one molecule of negative-sense single strand RNA coding for five to ten genes in a conserved order. The RNA is not infectious until packaged by the nucleocapsid protein and transcribed by the polymerase and co-factors. Reverse genetics approaches have answered fundamental questions about the biology of Mononegavirales. The lack of icosahedral symmetry and modular organization in the genome of these viruses has facilitated engineering of viruses expressing fluorescent proteins, and these fluorescent proteins have provided important insights about the molecular and cellular basis of tissue tropism and pathogenesis. Studies have assessed the relevance for virulence of different receptors and the interactions with cellular proteins governing the innate immune responses. Research has also analyzed the mechanisms of attenuation. Based on these findings, ongoing clinical trials are exploring new live attenuated vaccines and the use of viruses re-engineered as cancer therapeutics.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Christian K
authors.initials: CK
authors.lastname: Pfaller
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Cattaneo.Roberto@mayo.edu.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cattaneo
authors.affiliation: Department of Microbiology and Immunology, Philadelphia, PA 19107, USA; Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: Matthias.schnell@jefferson.edu.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell
mesh_terms: D054884:Host-Pathogen Interactions; D006801:Humans; D018096:Mononegavirales / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D009369:Neoplasms / Q000628:therapy; D050130:Oncolytic Virotherapy / Q000379:methods; D059386:Reverse Genetics; D014613:Vaccines, Attenuated / Q000276:immunology / Q000302:isolation & purification; D056189:Viral Tropism; D014765:Viral Vaccines / Q000276:immunology / Q000302:isolation & purification; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: Attenuation; Cancer therapy; Innate immunity; Mononegavirales; Pathology; Receptors; Reverse genetics; Tropism; Vaccines