Comparative analysis of G1 glycoprotein-coding sequences of Cache Valley virus (Bunyaviridae: Bunyavirus) isolates

Abstract

The complete 4463 nucleotide sequence for the medium segment viral RNA of Cache Valley virus has been cloned and sequenced in four isolates; in addition, the G1 glycoprotein extracellular coding domains are completed for nine additional isolates, including two subtypes, Ft. Sherman (86MSP18) and Tlacotalpan (61D240) viruses. The 13 represent isolations spanning over 45 years and a large geographic area, including the U.S., Mexico, Canada, and Panama. Glycosylation sites in G1 are generally conserved among all except the Ft. Davis, Panama (90P686) isolate, which loses a site otherwise conserved within the serogroup. Comparison of the G1 coding regions indicates a number of shared amino acid substitutions within a centrally located 70 amino acid hypervariable domain, which seems to fall outside the primary antigenic domains of G1, most of which are found within the amino half of the protein, while a less antigenic region is predicted for the carboxyl half of the protein encoded beyond the hypervariable domain. Numerous amino acid substitutions are found within various antigenic regions, which may be an indication of altered neutralization or hemagglutination sites. Putative phosphorylation sites are indicated, most of which are well conserved, with the exception of the absence of a specific protein kinase C site for the prototype (6V633) virus isolated in Utah. The overall nucleotide identity between isolates ranges from 91% (Ft. Sherman subtype, 86MSP18) to 99.4% (North Dakota, 1508-A52) as compared to the prototype virus (Utah, 6V633).