Regions of conservation and divergence in the 3′ untranslated sequences of genomic RNA from Ross River virus isolates

Abstract

The 3′ untranslated (UT) sequences of the genomic RNAs of five geographic variants of the alphavirus Ross River virus (RRV) were determined and compared with the 3′ UT sequence of RRV T48, the prototype strain. Part of the 3′ UT region of Getah virus, a close serological relative of RRV, was also sequenced. The RRV 3′ UT region varies markedly in length between variants. Large deletions or insertions, sequence rearrangements and single nucleotide substitutions are observed. A sequence tract of 49 to 58 nucleotides, which is repeated as four blocks in the RRV T48 3′ UT region, occurs only once in the 3′ UT region of one RRV strain (NB5092), indicating that the existence of repeat sequence blocks is not essential for RRV replication. However, the precise sequence of the 3′ proximal copy of the repeat block and its position relative to the poly(A) tail were identical in all RRV isolates examined, suggesting that it has an important role in RRV replication. Nucleotide substitutions between RRV variants are distributed non-randomly along the length of the 3′ UT region. The sequence of 120 to 130 nucleotides adjacent to the poly(A) tail is strongly conserved. Getah virus RNA contains three repeat sequence blocks in the 3′ UT region. These are similar in sequence to those in RRV RNA but differ in their arrangement. Homology between the RRV and Getah 3′ UT sequences is greatest in the 3′ proximal repeat sequence block that shows three differences in 49 nucleotides. The 3′ proximal repeat in Getah RNA occurs at the same position, relative to the poly(A) tail, as in all RRV variants. The RRV and Getah virus 3′ UT sequences show extensive homology in the region between the 3′ proximal repeat and the poly(A) tail but, apart from the repeat blocks themselves, they show no significant homology elsewhere.