Whole genome sequencing of live attenuated bovine adenovirus type 7 vaccine strain TS-GT reveals biomarkers for virulence attenuation
Abstract Bovine adenovirus type 7 (BAdV-7) is one of the most important respiratory and enteric pathogens in the cattle industry. Although live attenuated vaccines are used to control the virus in Japan, limited information is available on the genomic regions that determine viral pathogenicity. Here we analyzed the attenuated strain TS-GT after isolation of the virus from the hexavalent bovine respiratory disease vaccine Cattlewin-6 lot #40-1. The complete genome sequence of TS-GT was determined using next-generation sequencing. The genome is 30,052 bp long and contains 45-bp inverted terminal repeats (ITR) and 30 predicted genes. A genome sequence comparison showed that 99.9% of the TS-GT genome is identical to the prototypic and pathogenic BAdV-7 strain Fukuroi; however, the TS-GT genome contains a novel mutation and four indels. A mutation in TS-GT of the minor capsid protein pVI causes an amino acid change, and possibly induces an alteration of its membrane-lytic function; this may underlie the temperature-specific growth characteristic of this strain. A 19-bp insertion in the 3’ ITR may affect its promoter activity and change the expression of downstream coding genes. In this way, the insertion may play important roles in the attenuation of the virus. Although further mutational and functional analyses are required, our results provide insights into the molecular basis of BAdV-7 attenuation and open new avenues for future analyses.