Actin Used to Spread Adenovirus Infection

Their findings were published in the November 29, 2002, issue of the Journal of Biological Chemistry.

The complex ultra-structure of cells, their shape and internal structure, and cellular motility are largely supported by filaments of actin. A tangle of cross-linked actin filaments fills the cytoplasm of most types of cells, forming a cytoskeleton that gives the cell shape and form and provides a scaffold for organization. Tightly bundled actin filaments provide a sturdy backbone to extrude structures from the cell surface, such as the pseudopods used by amoebas and microvilli of intestinal cells, which extend into the digestive tract and absorb nutrients.


The researchers, from the U.S. Department of Energy's Brookhaven National Laboratory (Upton, NY, USA), have found that adenoviruses can use actin to destroy cells and allow new viruses to escape to infect others. "This is a new and philosophically interesting way for a virus to escape from cells,” explained senior author, Brookhaven biologist Dr. Walter Mangel. "In essence, a protein in the infected cells can serve as the seed of the cells' own destruction.”


Actin was suspected of being a cellular cofactor for adenovirus proteinase (AVP), an inactive viral proteinase, because the C terminus of actin is homologous to a viral cofactor for AVP. AVP was shown to bind to the C terminus of actin, and in doing so AVP exhibited full enzymatic activity. In vitro, actin was a cofactor in the cleavage of cytokeratin 18 by AVP. The proteinase alone could not cleave cytokeratin 18, but in the presence of actin, AVP cleaved cytokeratin 18. Furthermore, actin itself was shown to be a cofactor and a substrate for its own destruction in that it was cleaved by AVP in vitro.

"When actin and other cytoskeleton proteins are destroyed,” said Dr. Mangel, "a cell loses its shape and eventually breaks open, allowing the newly synthesized virus particles to escape and infect other cells.”



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Brookhaven National Laboratory