title: Identification of viral genomic elements responsible for rabies virus neuroinvasiveness.
abstract: Attenuated tissue culture-adapted and natural street rabies virus (RV) strains differ greatly in their neuroinvasiveness. To identify the elements responsible for the ability of an RV to enter the CNS from a peripheral site and to cause lethal neurological disease, we constructed a full-length cDNA clone of silver-haired bat-associated RV (SHBRV) strain 18 and exchanged the genes encoding RV proteins and genomic sequences of this highly neuroinvasive RV strain with those of a highly attenuated nonneuroinvasive RV vaccine strain (SN0). Analysis of the recombinant RV (SB0), which was recovered from SHBRV-18 cDNA, indicated that this RV is phenotypically indistinguishable from WT SHBRV-18. Characterization of the chimeric viruses revealed that in addition to the RV glycoprotein, which plays a predominant role in the ability of an RV to invade the CNS from a peripheral site, viral elements such as the trailer sequence, the RV polymerase, and the pseudogene contribute to RV neuroinvasiveness. Analyses also revealed that neuroinvasiveness of an RV correlates inversely with the time necessary for internalization of RV virions and with the capacity of the virus to grow in neuroblastoma cells.
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
authors.forename: Milosz
authors.initials: M
authors.lastname: Faber
authors.forename: Rojjanaporn
authors.initials: R
authors.lastname: Pulmanausahakul
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nagao
authors.forename: Mikhail
authors.initials: M
authors.lastname: Prosniak
authors.forename: Amy B
authors.initials: AB
authors.lastname: Rice
authors.forename: Hilary
authors.initials: H
authors.lastname: Koprowski
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dietzschold
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D005260:Female; D016679:Genome, Viral; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D011247:Pregnancy; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D011818:Rabies / Q000821:virology; D011820:Rabies virus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D011995:Recombination, Genetic; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
chemical_list: D012367:RNA, Viral