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Processing of vimentin occurs during the early stages of adenovirus infection
Abstract:
Evidence is presented that a fraction of vimentin, a component of cytoskeleton recently found to be associated with intracytoplasmic, migrating adenovirus type 2 (Ad2), is processed into smaller polypeptides at early times after infection. The extent of vimentin cleavage appears to depend upon both the multiplicity of infection and the adenovirus serotype. Ad2, Ad5, Ad4, and Ad9 induced similar vimentin cleavage in infected cells, whereas Ad3, Ad7, and Ad12, for which most infecting particles are found sequestered within phagosomes, induced very little, if any, vimentin breakdown. This suggests that vimentin processing is in some way related to the number of virus particles migrating through the cytoplasm. Experiments performed in vitro and in vivo with adenovirus temperature-sensitive mutants H2 ts1 and H2 ts112 and UV-inactivated wild-type Ad2 indicated that vimentin processing is due to a nonvirion, cytoskeleton-associated, proteolytic enzyme activated by adenovirus and sharing characteristics with the protease described by Nelson and Traub (W.J. Nelson and P. Traub, J. Cell Sci. 57:25-49, 1982). The activity of this protease appears to be required for productive infection by adenovirus serotypes 2 and 5 (subgroup C), 4 (subgroup E), and 9 (subgroup D) but not by the oncogenic serotypes 3 and 7 (subgroup B) and 12 (subgroup A).
Insights
Adenovirus infection triggers the breakdown of vimentin, a cytoskeletal protein, via an activated protease. This vimentin processing is essential for productive infection by certain adenovirus serotypes, but not others.
Area of Science:
- Cell Biology
- Virology
- Biochemistry
Background:
- Vimentin is a cytoskeletal protein associated with intracytoplasmic adenovirus type 2 (Ad2) migration.
- Adenovirus infection involves virus particles interacting with and potentially altering the host cell cytoskeleton.
Purpose of the Study:
- To investigate the processing of vimentin during adenovirus infection.
- To identify the mechanism and requirements for vimentin cleavage.
- To determine the role of vimentin processing in adenovirus infectivity.
Main Methods:
- Infection of cells with various adenovirus serotypes and mutants.
- Analysis of vimentin cleavage by polyacrylamide gel electrophoresis.
- In vitro and in vivo experiments using temperature-sensitive and UV-inactivated adenovirus.
- Characterization of the protease involved in vimentin processing.
Main Results:
- A fraction of vimentin is cleaved into smaller polypeptides early after Ad2 infection.
- Vimentin cleavage extent depends on infection multiplicity and adenovirus serotype; subgroups A, B serotypes induce minimal cleavage, while C, D, E serotypes induce significant cleavage.
- Vimentin processing is mediated by a cytoskeleton-associated proteolytic enzyme activated by adenovirus, not a viral protein.
- This protease activity is crucial for productive infection by Ad2, Ad5, Ad4, Ad9 but not Ad3, Ad7, Ad12.
Conclusions:
- Adenovirus-induced vimentin processing is mediated by a host cell protease activated during infection.
- The efficiency of vimentin cleavage correlates with the ability of certain adenovirus serotypes to productively infect cells.
- Vimentin processing appears to be a critical host-cell-related factor for the replication of specific adenovirus subgroups.