C-terminal truncation of the transmembrane protein of an attenuated lentiviral vaccine alters its in vitro but not in vivo replication and weakens its potential pathogenicity.

The research paper examines how a specific modification in a transmembrane protein in a lentiviral vaccine strain impacts its replication and pathogenicity, both in vitro and in vivo. It was discovered that although the alteration reduces the vaccine’s replication capacity in laboratory tests, it doesn’t curtail its ability to reproduce within a living host, yet lessens its potential pathogenicity overall.

Key Findings

• The research initially identified a recurring premature stop codon at a particular position in the gene of gp45 transmembrane protein (TM) of an attenuated equine infectious anemia virus (EIAV) vaccine strain. This stop codon caused truncation, or shortening, of the C-terminus – the end part of the protein structure.
• A recombinant virus, dubbed EIAV(FDDV-TM36), was engineered to carry this TM truncation. It was observed that this virus showed diminished replication capability when compared to a prototype virus (EIAV(FDDV)3-8) when cultivated within equine or donkey monocyte-derived macrophages. The modified virus also had a reduced ability to trigger apoptosis, or programmed cell death.
• Despite its limited replication ability in vitro, EIAV(FDDV-TM36) managed to generate similar plasma viral load levels as the prototype virus within live horses without inducing clinical symptoms of EIA.
• The study further investigated the in vivo effects of the TM truncation by transiently suppressing the immune response in the inoculated horses using dexamethasone. It was found that the viral load in the modified virus did not increment statistically, unlike hosts with the prototype virus. A notable increase in neutralizing antibodies was only observed in the group of horses with the prototype virus after immunosuppression.

Implications and Conclusion

• The findings suggest that the truncation of the C-terminus of transmembrane protein impacts the virus’s replication ability negatively in controlled laboratory conditions but does not change its live host replication efficiency.
• However, this truncation appears to lessen the pathogenicity of the virus, as evidenced by the modified virus’s inability to escalate in viral load after introducing immunosuppression.
• The researchers concluded that the host’s immune response might be integral to controlling the equal replication levels of the truncated and prototype transmembrane protein in vivo.