Sequence determination and molecular analysis of two strains of bovine parainfluenza virus type 3 that are attenuated for primates

The Kansas/15626/84 (Ka) and Shipping Fever (SF) strains of bovine parainfl uenza virus type 3 (BPIV3) replicate less efficiently than human PIV3 (HPIV 3) in the upper and lower respiratory tract of rhesus monkeys, and BPIV3 Ka is also highly attenuated in humans and is in clinical trials as a candida te vaccine against HPIV3. To initiate an investigation of the genetic basis of the observed attenuation phenotype of BPIV3 in primates, the complete g enomic sequences of Ka and SF genomes were determined and compared to those of BPIV3 strain 910N and two HPIV3 strains, JS and Wash/47885/57. There is a high degree of identity between the five PIV3 viruses in their 55 nucleo tide (nt) leader (83.6%) and 44 nt trailer (93.2%) sequences. The five viru ses display amino acid sequence identity ranging from 58.6% for the phospho protein to 89.7% for the matrix protein. Interestingly, the majority of ami no acid residues found to be variable at a given position in a five-way pro tein alignment are nonetheless identical within the viruses of either host species (BPIV3 or HPIV3). These host-specific residues might be products of distinct selective pressures on BPIV3 and HPIV3 during evolution in their respective hosts. These host-specific sequences likely include ones which a re responsible for the host range differences, such as the efficient growth of BPIV3 in bovines compared to its restricted growth in primates. It shou ld now be possible using the techniques of reverse genetics to import seque nces from BPIV3 into HPIV3 and identify those nt or protein sequences which attenuate HPIV3 for primates. This information should be useful in underst anding virus-host interactions and in the development of vaccines to protec t against HPIV3-induced disease.