[Mutations in the US2 and glycoprotein B genes of the equine herpesvirus 1 vaccine strain RacH have no effects on its attenuation].

The research article explains a study conducted to determine whether mutations in the US2 and glycoprotein B genes of the equine herpesvirus 1 (EHV-1) vaccine strain RacH affect its attenuation – or loss of strength/virulence. The researchers discovered that these mutations had no effect on the virus’s apathogenicity (non-disease causing ability), which instead was primarily due to the absence of the IR6 gene and protein.

Background and Purpose of Research

• The focus of this study is a modified live vaccine strain of EHV-1, known as RacH, which has been found to be apathogenic in lab animals and its natural host, indicating its safety as a vaccine strain.
• RacH’s apathogenicity is attributed to multiple serial passages of the virus in heterologous (different species) cells, which led to several genomic changes in comparison to its virulent parent strain, RacL11.
• Previous research pointed to the absence (or loss) of the IR6 gene in RacH as being linked to its diminished virulence, but noted additional significant mutations within the US2 gene and the glycoprotein B (gB) gene. The present article seeks to evaluate the relevance of these mutations to the RacH strain’s attenuation.

Research Methodology

• The scientists constructed various recombinant versions of the EHV-1 virus to settle this query. They did this by swapping the mutated genes in RacH with the wild-type US2 gene or the wild-type gB gene from RacL11.
• In an inverse experiment, they also created a RacL11 recombinant that expressed the mutated (RacH) gB to observe any change in virulence.
• All recombinant viruses were then evaluated for their virulence in the EHV-1 mouse model.

Research Findings

• The results demonstrated that introducing the RacL11 US2 gene into the RacH virus did not restore any virulence. Mice infected with this recombinant displayed no typical signs of EHV-1-caused disease including symptoms and weight loss.
• Similarly, the swapping of gB genes between the RacL11 and RacH strains did not significantly alter their virulence profiles.

Conclusion

• Based on these findings, the researchers concluded that the attenuation of the EHV-1 vaccine strain RacH is primarily caused by the absence of the IR6 gene and protein.
• The multiple mutations observed in the US2 and gB genes of the RacH strain do not contribute to its loss of virulence, establishing that not all genomic changes necessarily affect a virus’s pathogenicity.