Sequence of the genome RNA of rubella virus: Evidence for genetic rearrangement during togavirus evolution

Abstract

The nucleotide sequence of the rubella virus (RUB) genomic RNA was determined. The RUB genomic RNA is 9757 nucleotides in length [excluding the poly(A) tail] and has a G/C content of 69.5%, the highest of any RNA virus sequenced to data. The RUB genomic RNA contains two long open reading frames (ORFs), a 5'-proximal ORF of 6656 nucleotides and a 3'-proximal ORF of 3189 nucleotides which encodes the structural proteins. Thus, the genomic organization of RUB is similar to that of alphaviruses, the other genus of the Togavirus family, and the 5'-proximal ORF of RUB therefore putatively codes for the nonstructural proteins. Sequences homologous to three regions of nucleotide sequence highly conserved among alphaviruses (a stem-and-loop structure at the 5' end of the genome, a 51-nucleotide conserved sequence near the 5' end of the genome, and a 20-nucleotide conserved sequence at the subgenomic RNA start site) were found in the RUB genomic RNA. Amino acid sequence comparisons between the nonstructural ORF of RUB and alphaviruses revealed only one short (122 amino acids) region of significant homology, indicating that these viruses are only distantly related. This region of homology is located at the NH2 terminus of nsP3 in the alphavirus genome. The RUB nonstructural protein ORF contains two global amino acid motifs conserved in a large number of positive-polarity RNA viruses, a motif indicative of helicase activity and a motif indicative of replicase activity. The order of the helicase motif and the nsP3 homology region in the RUB genome is reversed with respect to the alphavirus genome indicating that a genetic rearrangement has occurred during the evolution of these viruses.

The phylogeny of RNA-dependent RNA polymerases of positive-strand RNA viruses

“…The sequences were from the Swissprot database (Release 14), except those of ACLSV (German et al,I990), BaYMV (Kashiwazaki et aL, 1990), BYV (Agranovsky et al, 1991a), HCV (Houghton et al, 1989), BVDV (Collett et al, 1988), RCNMV (Xiong & Lommel, 1989), TBEV (Pletnev et al,[989), HEV (Reyes et al, 1990;G. Reyes & D. Bradley, personal communication), RuV (Dominguez et al, 1990), MHV and BEV (Snijder et al, 1990). Closely related sequences were omitted from the analysis, e.g.…”

Intracellular transport of rubella virus structural proteins expressed from cloned cDNA

“…58000) and E2 (the heterogeneous glycosylation of which leads to a broad band of Mr 42K to 47K on SDS-PAGE) (Bowden & Westaway, 1984;Kalkkinen et al, 1984;Oker-Blom et al, 1983, 1984Waxham & Wolinsky, 1983). This envelope surrounds a nucleocapsid consisting of the 9.8 kb (Dominguez et al, 1990) genome encased in a protein shell made up of a number of copies of the third structural protein, C (approx. Mr 34K) (Ho-Terry & Cohen, 1982;Oker-Blom et al, 1984;Waxham & Wolinsky, 1983).…”

“…Although showing only very minor sequence homology to the alphaviruses (Dominguez et al, 1990), RV has a similar replication strategy, in that the 5' end of the t Present address: Institute of Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Woking, Surrey GU24 0NF, U.K.…”

Rubella virus capsid protein structure and its role in virus assembly and infection

“…Vaccination has been very successful in controlling RV infection; however, the virus is still endemic in many areas of the world (1,2). RV is an enveloped virus with a 9.6-kb single-stranded, positive-sense RNA genome (1,3). The virions have particle diameters ranging from 600 to 800 Å, with most of the spherical virions having a diameter of about 700 Å (4).…”