Adenovirus inhibition of cell translation facilitates release of virus particles and enhances degradation of the cytokeratin network.
Infection of animal cells by a number of viruses generally results in an array of metabolic defects, including inhibition of host DNA, RNA, and protein synthesis, and morphological alterations known as cytopathic effects. For adenovirus infection there is a profound loss of cell structural integrity and a marked inhibition of host protein synthesis, the latter generally assumed necessary to enhance virus production. We examined the purpose of viral inhibition of cell translation and found that it was related in part to cytopathic wasting of infected cells. We show that viral shutoff of host translation promotes destruction of the intermediate filament network, particularly cytokeratins which are proteolysed at keratins K7 and K18 by the adenovirus late-acting L3 23-kDa proteinase. We found that if adenovirus is prevented from inhibiting cell translation, the intermediate filament network remains relatively intact, keratin proteins are still synthesized, and cells possess an almost normal morphological appearance and lyse poorly, reducing the release of nascent virus particles by several hundredfold. Remarkably, in tissue culture cells the accumulation of late viral structural proteins is only marginally reduced if host translation shutoff does not occur. Thus, a surprising major function for adenovirus inhibition of cellular protein synthesis is to enhance impairment of cellular structural integrity, facilitating cell lysis and release of progeny adenovirus particles.
Zhang
Y
Y
Department of Biochemistry, New York University School of Medicine, New York 10016.
Schneider
R J
RJ
D015075:2-Aminopurine / Q000494:pharmacology; D000260:Adenoviruses, Human / Q000187:drug effects / Q000254:growth & development*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral; D006801:Humans; D007382:Intermediate Filaments / Q000187:drug effects / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism*; D014176:Protein Biosynthesis; D014746:Vimentin / Q000378:metabolism; D014764:Viral Proteins
D014746:Vimentin; D014764:Viral Proteins; D015075:2-Aminopurine; D007633:Keratins; D003546:Cysteine Endopeptidases; C082284:L3 23K protein, adenovirus