Loss of stress response as a consequence of viral infection: implications for disease and therapy

Abstract

Herein, we propose that viral infection can induce a deficient cell stress response and thereby impairs stress tolerance and makes tissues vulnerable to damage. Having a valid paradigm to address the pathological impacts of viral infections could lead to effective new therapies for diseases that have previously been unresponsive to intervention. Host response to viral infections can also lead to autoimmune diseases like type 1 diabetes. In the case of Newcastle disease virus, the effects of viral infection on heat shock proteins may be leveraged as a therapy for cancer. Finally, the search for a specific virus being responsible for a condition like chronic fatigue syndrome may not be worthwhile if the disease is simply a nonspecific response to viral infection.

Fig. 1

Comparison of protein synthesis in uninfected cultured chicken embryo cells and cultures infected at moi = 5 PFU/ml with virulent NDV-AV, avirulent NDV strains B1-Hitchner, and NJ-LaSota. The cultures were incubated for 6 h at 40.5 °C, then radiolabeled for 30 min with 35S-methionine. Extracts were prepared in gel sample buffer, and polypeptides were separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Extracts of radioactively labeled polypeptides from uninfected and infected cells labeled with radioactive methionine were compared. a Fluorogram of a 7 % polyacrylamide gel. Lane 1 uninfected cultures, lane 2 strain AV infected, lane 3 strain B1-Hitchner infected, lane 4, strain NJ-LaSota infected. The positions of avian Hsp70, Grp78, and Hsp90 are marked with the arrows on the right side. These avian stress proteins were verified by peptide mapping (Collins and Hightower 1982). Left side arrows mark major NDV polypeptides: L large polypeptide, the transcriptase, HN haemagglutinin-neuraminidase glycopolypeptide, Fo the precursor to the fusion glycopolypeptide, F fusion glycopolypeptide, NP nucleocapsid polypeptide, M matrix polypeptide. The position of cellular actin is marked as well. b Portion below 46 kDa of a fluorogram of a 9 % polyacrylamide gel on which the extracts described in a were separated in order to retain the small Hsp23 on the gel for comparison. Lane 1 strain AV, lane 2 strain NJ-LaSota, lane 3 strain B1-Hitchner, lane 4 cultures treated with the arginine analog canavanine to induce authentic cellular stress proteins (Hsps) including avian Hsp23 (equivalent to mammalian HspB1); lane 5 uninfected, untreated control cultures. The NDV matrix polypeptide position and that of cellular actin are marked as well

Fig. 2

Interferon, PKR, and eIF2α mediate the effect of viral infection on protein translation including Hsp 70