Fibronectin and viral pathogenesis

Fibronectin is a dimeric high-molecular-weight glycoprotein composed of two similar but not identical subunits. Differences have been observed between plasma and cell-derived fibronectins, and molecular and sequencing studies have revealed a domain structure. The characteristic features of fibronectin include its various molecular and biologic interactions, which can be assigned to the different domains of the molecule. Fibronectin was originally discovered as a protein missing from the surfaces of virus-transformed cells. The importance of functional oncogenes in the loss of extracellular matrices was later established in a number of studies using virus mutants that are temperature-sensitive for transformation. The loss of the extracellular matrix appears to be a result of multiple events in cells but is not a prerequisite for malignant growth in vivo. There appear to be multiple transformed phenotypes, and the loss of extracellular fibronectin may be due in part to proteolytic activity by the cells and other alterations caused by functioning oncogenes. The wide distribution of tissue and soluble forms of fibronectin offers multiple occasions for interactions with other molecules. Binding of fibronectin to viruses and purified viral proteins has been observed in a number of studies. Neuraminidase-sensitive virus-binding sites in the fibronectin molecule have tentatively been identified. Fibronectin also is capable of binding to various complement components, possibly making clearance of viral antigen-antibody-complement complexes, which are observed in the circulation during viral infection, more rapid. The virus-binding ability of fibronectin may play a role in modifying viral infections in the body.