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Matrix protein and glycoproteins F and H of Peste-des-petits-ruminants virus function better as a homologous complex
M Mahapatra1, S Parida1, M D Baron1
1Institute for Animal Health, Pirbright, Woking, Surrey GU24 0NF, UK.
Abstract:
The matrix (M) protein of paramyxoviruses forms an inner coat to the viral envelope and serves as a bridge between the surface glycoproteins (F and H) and the ribonucleoprotein core. Previously, a marker vaccine (RPV-PPRFH) was produced for the control of peste des petits ruminants (PPR) disease, where the F and H genes of Rinderpest virus (RPV) were replaced with the equivalent genes from Peste-des-petits-ruminants virus (PPRV); however, this virus grew poorly in tissue culture. The poor growth of the RPV-PPRFH chimeric virus was thought to be due to non-homologous interaction of the surface glycoproteins with the internal components of the virus, in particular with the M protein. In contrast, replacement of the M gene of RPV with that from PPRV did not have an effect on the viability or replication efficiency of the recombinant virus. Therefore, in an effort to improve the growth of the RPV-PPRFH virus, a triple chimera (RPV-PPRMFH) was made, where the M, F and H genes of RPV were replaced with those from PPRV. As expected, the growth of the triple chimera was improved; it grew to a titre as high as that of the unmodified PPRV, although comparatively lower than that of the parental RPV virus. Goats infected with the triple chimera showed no adverse reaction and were protected from subsequent challenge with wild-type PPRV. The neutralizing-antibody titre on the day of challenge was approximately 17 times higher than that in the RPV-PPRFH group, indicating RPV-PPRMFH as a promising marker-vaccine candidate.
Insights
Developing a new peste des petits ruminants (PPR) vaccine, RPV-PPRMFH, improved viral growth and goat protection. This triple chimera shows promise as a marker vaccine candidate for PPR disease control.
Area of Science:
- Virology
- Immunology
- Veterinary Medicine
Background:
- Paramyxovirus matrix (M) protein is crucial for viral structure and assembly.
- Previous chimeric vaccines (RPV-PPRFH) for peste des petits ruminants (PPR) exhibited poor tissue culture growth.
- M protein interactions with surface glycoproteins were hypothesized to cause poor growth in RPV-PPRFH.
Purpose of the Study:
- To improve the growth and efficacy of a peste des petits ruminants (PPR) marker vaccine.
- To investigate the role of the matrix (M) protein in chimeric virus replication.
- To develop a more effective vaccine candidate for PPR disease.
Main Methods:
- Construction of a triple chimeric virus (RPV-PPRMFH) by replacing M, F, and H genes of Rinderpest virus (RPV) with those from Peste-des-petits-ruminants virus (PPRV).
- Evaluation of viral growth in tissue culture.
- Assessment of vaccine efficacy in goats, including protection against wild-type PPRV challenge and antibody response.
Main Results:
- The triple chimera (RPV-PPRMFH) demonstrated improved growth in tissue culture compared to the RPV-PPRFH chimera.
- RPV-PPRMFH grew to titers comparable to unmodified PPRV, though lower than parental RPV.
- Goats vaccinated with RPV-PPRMFH showed no adverse effects and were protected from PPRV challenge, with significantly higher neutralizing antibody titers.
Conclusions:
- Replacing M, F, and H genes of RPV with PPRV counterparts enhances chimeric virus growth.
- The triple chimera RPV-PPRMFH is a promising candidate for a peste des petits ruminants (PPR) marker vaccine.
- RPV-PPRMFH elicits a robust immune response and provides protection against PPRV infection.
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