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.reverse genetics ͉ pathogenicity ͉ internalization

Molecular and immunogenic characterization of BHK-21 cell line adapted CVS-11 strain of rabies virus and future prospect in vaccination strategy

“…It is reported that the rabies vaccine failure may occur due to genetic difference between local virus isolates and vaccine strains in use and it could be overcome by developing vaccine strains from locally circulating viruses [1,16]. Therefore, the best vaccine strain is one that is as closely related as possible to the street viruses circulating within the specific geographical location [3,16,19]. Nucleoprotein gene based phylogenetic analysis revealed the similar findings as for G gene.…”

Animal Rabies in Massachusetts, 1985–2006

“…Rabies is transmitted to humans primarily through the saliva and neurologic tissues of infected animals by direct or indirect exposure (Fishbein and Robinson, 1993;Rupprecht et al, 1996;Faber et al, 2004) and the disease is almost invariably fatal (Hattwick et al, 1972;Willoughby et al, 2005). There have been very rare reported cases of survival after the development of rabies (Centers for Disease Control [CDC], 2004).…”

Determination and Molecular Analysis of the Complete Genome Sequence of Two Wild-Type Rabies Viruses Isolated from a Haematophagous Bat and a Frugivorous Bat in Brazil

“…In recent years, there have been several reports on the complete genomic sequences of wild-type RABVs and other genotypes (GTs) [4,6,17,18,22,34], as well as a complete genome analysis of a RABV isolated from Brazilian wild fox [21]. Analyses of genome sequences of wildtype RABVs provide useful information for understanding genetic and biological characteristics of RABVs prevalent in the wild.…”