Rubella virus glycoprotein interaction with the endoplasmic reticulum calreticulin and calnexin.
Very little is known about the cellular factors that are required for the maturation of rubella virus glycoproteins (E2 and E1) in the endoplasmic reticulum of the infected cell. In the present study, we established the interaction of the ER chaperone proteins, calreticulin and calnexin, with the RV E1 and E2 proteins in cells stably expressing the viral proteins. The interaction between E2 and calnexin was significantly higher than with calreticulin. In pulse-chase experiments, the half-life of the E2-calnexin was >45 min, whereas the half-life of the calreticulin-E2 interaction was approximately 10 min. Tunicamycin and castanospermine treatments altered the mobilities of intracellular E1 and E2, due to either lack of oligosaccharide ligand addition or trimming of terminal glucose residues, respectively. Further, the drug treatments resulted in a loss of E1 and E2 interaction with calreticulin or calnexin, thereby demonstrating that the interaction is through monoglucosylated forms of RV proteins. These studies suggest that the interaction of RV glycoproteins with the ER chaperone proteins is essential for their maturation in the endoplasmic reticulum.
Laboratory of Parasitic Biology and Biochemistry, Division of Allergenic Products and Parasitology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
H L
HL
Nakhasi
M
M
Ramanujam
C D
CD
Atreya
T C
TC
Hobman
N
N
Lee
A
A
Esmaili
R C
RC
Duncan
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D016466:CHO Cells / Q000187:drug effects / Q000821:virology; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D037281:Calnexin; D037282:Calreticulin; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000821:virology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism*; D007212:Indolizines / Q000494:pharmacology; D007700:Kinetics; D018832:Molecular Chaperones / Q000378:metabolism*; D011485:Protein Binding; D012261:Ribonucleoproteins / Q000378:metabolism*; D012412:Rubella virus / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000378:metabolism; D054836:Indolizidines
D000998:Antiviral Agents; D002135:Calcium-Binding Proteins; D037281:Calnexin; D037282:Calreticulin; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D007212:Indolizines; D018832:Molecular Chaperones; D012261:Ribonucleoproteins; D014415:Tunicamycin; D014759:Viral Envelope Proteins; C061826:E1 envelope protein, Rubella virus; C061827:E2 envelope protein, Rubella virus; C037806:castanospermine; D054836:Indolizidines