Amino acid substitutions in the structural or nonstructural proteins of a vaccine strain of equine arteritis virus are associated with its attenuation.

The study investigates how amino acid substitutions in the equine arteritis virus (EAV), specifically in its structural and nonstructural proteins, contribute to the virus’ attenuation or loss of virulence, utilising the comparison of various EAV strains and genetic alteration techniques.

Objectives and Methodology

• The primary aim of this research is to determine how specific amino acid substitutions in both the structural and nonstructural proteins of EAV influence its virulence in horses.
• This is done by comparing the genetic sequences of multiple EAV strains, from the highly virulent Bucyrus (VB) strain to a fully attenuated vaccine strain derived from it.
• In the course of the study, 13 amino acid changes associated with attenuation are identified, including four in the replicase proteins and nine in the structural proteins.
• Utilising reverse genetic techniques, these amino acid substitutions are introduced into a virulent infectious cDNA clone pEAVrVBS, derived from the VB strain.

Findings

• Upon inoculating horses with the genetically altered viruses, the research revealed that substitutions in either the replicase (nsp1, nsp2 and nsp7) or structural (GP2, GP4, GP5 and M) proteins led to the attenuation of the virulent VB strain.
• This demonstrates directly that these specific alterations in the amino acid sequence weaken the virus’s ability to cause disease in horses.
• Notably, the recombinant virus with changes in the structural proteins had a higher degree of attenuation compared to the recombinant virus with substitutions solely in the replicase proteins.

Implications

• These findings broaden our understanding of what genetic factors make a virus strain more or less virulent.
• They provide insights into how vaccine strains can be developed by genetically attenuating the virus.
• The results of this study have implications for the development of safer and more effective vaccines against equine arteritis virus and other similar viruses.