Related Experiment Videos
A protein serologically and functionally related to the group C E3 14,700-kilodalton protein is found in multiple
T M Horton1, A E Tollefson, W S Wold
1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322.
Abstract:
A 14.7-kilodalton protein (14.7K protein) encoded by the E3 region of group C adenoviruses has been shown to protect virus-infected fibroblasts from lysis by tumor necrosis factor (TNF) (L.R. Gooding, L.W. Elmore, A.E. Tollefson, H.A. Brady, and W.S.M. Wold, Cell 53:341-346, 1988). In this study we show that adenoviruses of other groups are also protected from TNF-induced cytolysis. Representative serotypes of groups A, B, D, and E produce a protein analogous to the 14.7K protein found in human group C adenoviruses. Deletion of this protein in group C viruses permits virus infection to induce cellular susceptibility to TNF killing. As with group C adenoviruses, cells infected with wild-type adenoviruses of other serotypes are not killed by TNF and are protected from lysis induced by TNF plus cycloheximide. However, cells are susceptible to TNF-induced lysis when infected with adenovirus type 4 mutants from which the 14.7K gene has been deleted. Although all known adenovirus serotypes infect epithelial cells, adenoviruses cause several diseases with various degrees of pathogenesis. Our findings suggest that the 14.7K protein provides a function required for the in vivo cytotoxicity of many adenoviruses independent of the site of infection or degree of pathogenesis.
Insights
Adenoviruses produce a 14.7K protein that protects infected cells from tumor necrosis factor (TNF) lysis. This protective protein is found across multiple adenovirus groups, suggesting a conserved role in viral pathogenesis.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Group C adenoviruses encode a 14.7-kilodalton (14.7K) protein that confers resistance to tumor necrosis factor (TNF)-induced cell lysis.
- The role of this protein in other adenovirus groups and its broader significance in viral pathogenesis were not fully understood.
Purpose of the Study:
- To investigate whether adenoviruses from other groups also produce a protein analogous to the 14.7K protein.
- To determine if this protein confers protection against TNF-induced cytolysis in various adenovirus serotypes.
- To assess the role of the 14.7K protein in adenovirus pathogenesis.
Main Methods:
- Analysis of protein expression in cells infected with representative serotypes from adenovirus groups A, B, D, and E.
- Generation and characterization of adenovirus mutants with deletions in the 14.7K gene.
- Assays to measure cellular susceptibility to TNF-induced lysis in infected and uninfected cells, with and without cycloheximide.
Main Results:
- Adenoviruses from groups A, B, D, and E were found to produce a protein analogous to the 14.7K protein.
- Deletion of the 14.7K gene in group C and type 4 adenoviruses rendered infected cells susceptible to TNF-induced lysis.
- Wild-type adenoviruses from various groups protected infected cells from TNF and TNF plus cycloheximide-induced lysis.
Conclusions:
- The 14.7K protein is a conserved viral factor across multiple adenovirus groups, providing protection against TNF-induced cytolysis.
- This protein plays a crucial role in the in vivo cytotoxicity of many adenoviruses, irrespective of the infection site or disease severity.
- The findings highlight the 14.7K protein as a significant factor in adenovirus pathogenesis.