Identification and characterization of the poliovirus-induced cleavage of microtubule-associated protein 4

Virus infection of a host cell usually results in characteristic morphological alterations in the cell, termed cytopathic effect. These effects are usually deleterious to the cell, often heralding its ultimate death. It has been known for many years that polioviruses, members of the Picornavirus family of viruses, cause distinctive and pronounced cytopathic effects in their host cells, resulting in the disruption and alteration of many cellular systems. However, the molecular basis for many of these alterations remains a mystery, despite many years of intense study.;Further characterization of this alteration revealed that the polioviral protease 3C mediates cleavage of MAP-4, likely at a site similar to known 3C cleavage sites in other substrates. The cleavage of MAP-4 is also shown to correlate with the "collapse" of microtubules in infected cells. The possible ramifications of such an effect with regard to microtubules, viral replication and other cellular systems are discussed. The study of MAP-4 cleavage may lead to new understanding of cytopathologic changes long observed, but poorly understood.;A monoclonal antibody, 25 C C1, was shown to recognize an antigen altered in poliovirus infected cells. The goal of this project was to identify the protein antigen and characterize the alteration mediated by poliovirus. Initial characterization of the 25 C C1 antigen revealed that it was a protein cleaved late in infection, and was associated with cytoskeletal structures. Cloning of the cDNA for the 25 C C1 antigen by immunoscreening revealed that isolates shared nearly 100% sequence homology with the previously published sequence for human microtubule-associated protein 4 (hMAP-4) (West et al, 1991, J. Biol. Chem. 266: 21886-21896). Purification of MAP-4 revealed that it is the protein recognized by the 25 C C1 antibody and altered during poliovirus infection.