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Updated: Jun 19, 2026
Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
The poxvirus A35 protein is an immunoregulator
Kristina E Rehm1, Gwendolyn J B Jones, Alice A Tripp
1Department of Microbiology and Immunology, East Carolina University Brody School of Medicine, Greenville, NC 27834, USA.
Abstract:
It was shown previously that the highly conserved vaccinia virus A35 gene is an important virulence factor in respiratory infection of mice. We show here that A35 is also required for full virulence by the intraperitoneal route of infection. A virus mutant in which the A35 gene has been removed replicated normally and elicited improved antibody, gamma interferon-secreting cell, and cytotoxic T-lymphocyte responses compared to wild-type virus, suggesting that A35 increases poxvirus virulence by immunomodulation. The enhanced immune response correlated with an improved control of viral titers in target organs after the development of the specific immune response. Finally, the A35 deletion mutant virus also provided protection from lethal challenge (1,000 50% lethal doses) equal to that of the wild-type virus. Together, these data suggest that A35 deletion viruses will make safer and more efficacious vaccines for poxviruses. In addition, the A35 deletion viruses will serve as improved platform vectors for other infectious diseases and cancer and will be superior vaccine choices for postexposure poxvirus vaccination, as they also provide improved kinetics of the immune response.
Insights
The vaccinia virus A35 gene enhances poxvirus virulence by suppressing immune responses. Removing this gene creates safer, more effective poxvirus vaccines and vectors.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- The vaccinia virus A35 gene is a conserved virulence factor in respiratory infections.
- A35's role in intraperitoneal infection and its mechanism of virulence modulation were previously unclear.
Purpose of the Study:
- To investigate the role of the vaccinia virus A35 gene in intraperitoneal infection.
- To determine the mechanism by which A35 influences poxvirus virulence.
- To evaluate the potential of A35 deletion mutants as vaccine candidates.
Main Methods:
- Generation of a vaccinia virus mutant lacking the A35 gene.
- Comparison of viral replication, immunogenicity, and protective efficacy between wild-type and A35 deletion mutant viruses in a mouse model.
- Assessment of antibody, gamma interferon-secreting cell, and cytotoxic T-lymphocyte responses.
Main Results:
- A35 deletion mutant virus replicated normally but elicited enhanced antibody, gamma interferon-secreting cell, and cytotoxic T-lymphocyte responses compared to wild-type virus.
- Enhanced immune responses correlated with improved control of viral titers in target organs.
- A35 deletion mutant provided protection from lethal challenge comparable to wild-type virus.
Conclusions:
- The vaccinia virus A35 gene contributes to virulence through immunomodulation.
- A35 deletion mutants represent safer and more efficacious vaccine candidates for poxviruses.
- A35 deletion viruses are promising platform vectors for other diseases and cancer, offering improved immune response kinetics.
