Adenovirus Endopeptidase and Its Role in Virus Infection

Abstract

Although adenoviruses were first described in 1953, significant progress on the study of viral proteins was only realized after the application of the newly discovered protein separation technique by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Metabolic labeling experiments using SDS-PAGE demonstrated the processing of several slightly larger precursor proteins into smaller and stable products (Anderson et al. 1973). Processing of RNA virus polyproteins was well known by this time, but the processing of individual viral proteins had only been described in bacteriophages (Murialdo and Siminovitch 1972). Studies with adenovirus temperature-sensitive mutants showed that processing was coordinately regulated and was linked to some late event in virus assembly, because all mutants were uniformly defective for processing. As most mutants fail to assemble virus particles, assembly appears to be a minimal requirement for precursor processing. That it is not a sufficient requirement is shown by some fiber mutants which assemble fiberless capsids in the absence of precursor processing (Falgout and Ketner 1988). The ts1 mutant was to become the paradigm of this late event. At the nonpermissive temperature, ts1 assembles virus particles which contain the genome and six unprocessed precursor proteins, namely pVI, pVII, pVIII, pIIIa, pµ, and preterminal protein, pTP (Weber 1976, 1990). Significantly, these particles are not infectious because they fail to uncoat (Mirza and Weber 1980; Miles et al. 1980).