Virus-induced Ca2+ influx extends survival of west nile virus-infected cells.
West Nile virus (WNV) infection leads to rapid and sustained Ca(2+) influx. This influx was observed with different strains of WNV and in different types of cells. Entry during virion endocytosis as well as through calcium channels contributed to the Ca(2+) influx observed in WNV-infected cells. Ca(2+) influx was not detected after infection with vesicular stomatitis virus (VSV) and occurred only through endocytosis in Sindbis virus-infected cells. Caspase 3 cleavage and activation of several kinases, including focal adhesion kinase (FAK), mitogen-activated extracellular signal-regulated protein kinase (ERK1/2), and protein-serine kinase B alpha (Akt), at early times after WNV infection were shown to be dependent on Ca(2+) influx. Although the activation of these kinases was sustained in virus-infected cells throughout infection, UV-inactivated WNV induced only a transient activation of FAK and ERK1/2 at early times after infection. The Ca(2+)-dependent FAK activation observed in WNV-infected cells was not mediated by alphavbeta3 integrins. Reduction of Ca(2+) influx at early times of infection by various treatments decreased the viral yield and delayed both the early transient caspase 3 cleavage and the activation of FAK, Akt, and ERK signaling. The results indicate that Ca(2+) influx is required for early infection events needed for efficient viral replication, possibly for virus-induced rearrangement of the endoplasmic reticulum (ER) membrane. Increased caspase 3 cleavage at both early (transient) and late times of infection correlated with decreased activation of the FAK and ERK1/2 pathways, indicating a role for these kinases in extending the survival of flavivirus-infected cells.
Department of Biology, Georgia State University, Atlanta, Georgia 30302-4010, USA.
Svetlana V
SV
Scherbik
Margo A
MA
Brinton
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D014901:West Nile Fever / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology* / Q000821:virology; D014902:West Nile virus / Q000235:genetics / Q000502:physiology*
D051416:Focal Adhesion Protein-Tyrosine Kinases; D053148:Caspase 3; D002118:Calcium