Related Experiment Video
Updated: Oct 15, 2026
Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
Sequence determination and molecular analysis of two strains of bovine parainfluenza virus type 3 that are attenuated
J E Bailly1, J M McAuliffe, M H Skiadopoulos
1National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892 USA.
Abstract:
The Kansas/15626/84 (Ka) and Shipping Fever (SF) strains of bovine parainfluenza virus type 3 (BPIV3) replicate less efficiently than human PIV3 (HPIV3) 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 candidate vaccine against HPIV3. To initiate an investigation of the genetic basis of the observed attenuation phenotype of BPIV3 in primates, the complete genomic 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 nucleotide (nt) leader (83.6%) and 44 nt trailer (93.2%) sequences. The five viruses display amino acid sequence identity ranging from 58.6% for the phosphoprotein to 89.7% for the matrix protein. Interestingly, the majority of amino acid residues found to be variable at a given position in a five-way protein 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 are responsible for the host range differences, such as the efficient growth of BPIV3 in bovines compared to its restricted growth in primates. It should now be possible using the techniques of reverse genetics to import sequences from BPIV3 into HPIV3 and identify those nt or protein sequences which attenuate HPIV3 for primates. This information should be useful in understanding virus-host interactions and in the development of vaccines to protect against HPIV3-induced disease.
Insights
Bovine parainfluenza virus type 3 (BPIV3) shows reduced replication in primates compared to human PIV3 (HPIV3). Genetic analysis reveals host-specific sequences potentially responsible for this difference, aiding vaccine development.
Area of Science:
- Virology
- Genomics
- Immunology
Background:
- Bovine parainfluenza virus type 3 (BPIV3) strains exhibit less efficient replication in primate respiratory tracts than human PIV3 (HPIV3).
- BPIV3 Ka strain is attenuated in humans and is a candidate vaccine for HPIV3.
- Understanding BPIV3's genetic basis for primate attenuation is crucial for vaccine development.
Purpose of the Study:
- To investigate the genetic factors underlying BPIV3's attenuated phenotype in primates.
- To compare the genomic sequences of BPIV3 and HPIV3 strains.
Main Methods:
- Determined and compared complete genomic sequences of BPIV3 (Ka, SF, 910N) and HPIV3 (JS, Wash/47885/57) strains.
- Analyzed nucleotide and amino acid sequence identities across viral proteins and regulatory regions.
Main Results:
- High sequence identity observed in leader and trailer regions (83.6% and 93.2%, respectively).
- Amino acid sequence identity varied from 58.6% (phosphoprotein) to 89.7% (matrix protein).
- Identified host-specific amino acid residues, suggesting distinct evolutionary pressures in bovine versus human hosts.
Conclusions:
- Host-specific residues likely contribute to host range differences and BPIV3's restricted growth in primates.
- Reverse genetics can be used to identify specific sequences responsible for HPIV3 attenuation in primates.
- Findings will advance understanding of virus-host interactions and HPIV3 vaccine development.
