Off-campus UNL users: To download campus access dissertations, please use the following link to log into our proxy server with your NU ID and password. When you are done browsing please remember to return to this page and log out.
Non-UNL users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Roles of an eukaryotic initiation factor 2-associated glycoprotein (p67) in regulation of protein synthesis in vaccinia virus infected animal cells
Abstract
An eukaryotic initiation factor 2 (eIF-2) associated 67 kDa glycoprotein (p67) plays a key role in protein synthesis initiation. In the present work I have studied the role of p67 in regulation of protein synthesis in vaccinia virus infected animal cells. Four different cell lines, KRC-7 (rat hepatoma), L929 (mouse fibroblast), and CV-1 (african green monkey kidney) cell lines were used for this study. These cell lines varied contained widely varying amounts of p67. KRC-7 cells have the highest concentration of endogenous p67 and these cells were resistant to vaccinia virus infection when a low viral titer (5 pfu/cell) was used to infect these cells. The L929 and CV-1 cells were infected under these conditions. KRC-7 cells could be infected only with a higher viral titer (25 pfu/cell) or when the endogenous p67 level was reduced either by serum starving these cells or by expression of p67-antisense DNA. Productive viral infection in all cases studied resulted in the activation of a latent p67-deglycosylase in the infected cells. Once activated, this p67-deglycosylase degiycosylated and consequently inactivated p67. This allowed active eIF-2 kinase(s) in these cells to phosphorylate eIF-2 leading to host protein synthesis shut-off. The virus then used the host machinery to synthesize its own proteins. The activation of p67-deglycosylase was observed within 30 mins of infection and probably preceding viral gene transcription. This indicated that p67-deglycosylase was host gene coded. The mechanism by which high p67 level in the KRC-7 cells prevents productive viral infection at a low viral titer is not clear. Several possibilities have been discussed in Chapter III. Viral DNA was detected in viral resistant KRC-7 cells. However, no viral mRNAs could be detected, indicating that the block in viral replication was at the level of viral gene transcription.
Subject Area
Biochemistry
Recommended Citation
Bose, Avirup, "Roles of an eukaryotic initiation factor 2-associated glycoprotein (p67) in regulation of protein synthesis in vaccinia virus infected animal cells" (1997). ETD collection for University of Nebraska-Lincoln. AAI9734608.
https://digitalcommons.unl.edu/dissertations/AAI9734608