Sequence analysis of the medium (M) segment of Cache Valley virus, with comparison to other Bunyaviridae

The complete sequence of the medium (M) segment of Cache Valley virus (CVV), a human neuropathogen, has been determined using a series of overlapping cDNA clones. The viral complementary-sense RNA is comprised of 4463 nucleotides which encodes a polyprotein precursor of 1435 amino acids, starting at AUG at bases 49-51 to a UGA stop codon at bases 4351-4353. This polyprotein-encoding sequence is arranged as G2-NSm-G1. The base composition of the segment is 34.9% A, 17.0% C, 19.4% G and 28.7% U. Comparison of the nucleotide sequence to the prototype Bunyamwera virus sequence shows an identity of 63%, indicating several differences exist within the individual coding regions, most notably within the NSm and G1 coding regions. Based on two presumed cleavage points within the precursor, the G2 glycoprotein, encoded from nt 94-951, is 286 amino acids long, and has two sites of potential glycosylation. NSm, encoded from nt 952-1476, is 175 amino acids, while the largest glycoprotein, G1, encoded from nt 1477-4350, consists of 958 amino acids, and has five potential glycosylation sites, two of which appear to be unique to CVV. The subsequent study of these glycosylation sites and potential differences between the sequence of this prototype CVV strain and other geographic isolates may suggest the means for improving detection of human infections as well as mapping differences in neurovirulence, neuroinvasiveness and other aspects of pathogenicity.