TY - JOUR
T1 - Tula hantavirus triggers pro-apoptotic signals of ER stress in Vero E6 cells
AU - Li, Xiao Dong
AU - Lankinen, Hilkka
AU - Putkuri, Niina
AU - Vapalahti, Olli
AU - Vaheri, Antti
N1 - Funding Information:
We thank Dr. Erkki Hölttä and Dr. Esa Kuismanen for discussion and providing antibodies. We are grateful to Ms. Leena Kostamovaara for expert technical assistance. This work was supported by grants from Academy of Finland, EU grants (QLK2-CT-1999-01119 and QLK2-CT-2002-01358), Magnus Ehrnrooth Foundation, and Sigrid Jusélius Foundation, Helsinki, Finland.
PY - 2005/3/1
Y1 - 2005/3/1
N2 - Tula virus is a member of the Hantavirus genus of the family Bunyaviridae. Viruses of this family have an unusual pattern of intracellular maturation at the ER-Golgi compartment. We recently found that Tula virus, similar to several other hantaviruses, is able to induce apoptosis in cultured cells [Li, X.D., Kukkonen, S., Vapalahti, O., Plyusnin, A., Lankinen, H., Vaheri, A., 2004. Tula hantavirus infection of Vero E6 cells induces apoptosis involving caspase 8 activation. J. Gen. Virol. 85, 3261-3268.]. However, the cellular mechanisms remain to be clarified. In this study, we demonstrate that the progressive replication of Tula virus in Vero E6 cells initiates several death programs that are intimately associated with ER stress: (1) early activation of ER-resident caspase-12; (2) phosphorylation of Jun NH2-terminal kinase (JNK) and its downstream target transcriptional factor, c-jun; (3) induction of the pro-apoptotic transcriptional factor, growth arrest- and DNA damage-inducible gene 153, or C/EBP homologous protein (Gadd153/chop); and (4) changes in the ER-membrane protein BAP31 implying cross-talk with the mitochondrial apoptosis pathway. Furthermore, we confirmed that a sustained ER stress was induced marked by an increased expression of an ER chaperone Grp78/BiP. Taken together, we have identified involvement of ER stress-mediated death program in Tula virus-infected Vero E6 cells which provides a new approach to understand the mechanisms in hantavirus-induced apoptosis.
AB - Tula virus is a member of the Hantavirus genus of the family Bunyaviridae. Viruses of this family have an unusual pattern of intracellular maturation at the ER-Golgi compartment. We recently found that Tula virus, similar to several other hantaviruses, is able to induce apoptosis in cultured cells [Li, X.D., Kukkonen, S., Vapalahti, O., Plyusnin, A., Lankinen, H., Vaheri, A., 2004. Tula hantavirus infection of Vero E6 cells induces apoptosis involving caspase 8 activation. J. Gen. Virol. 85, 3261-3268.]. However, the cellular mechanisms remain to be clarified. In this study, we demonstrate that the progressive replication of Tula virus in Vero E6 cells initiates several death programs that are intimately associated with ER stress: (1) early activation of ER-resident caspase-12; (2) phosphorylation of Jun NH2-terminal kinase (JNK) and its downstream target transcriptional factor, c-jun; (3) induction of the pro-apoptotic transcriptional factor, growth arrest- and DNA damage-inducible gene 153, or C/EBP homologous protein (Gadd153/chop); and (4) changes in the ER-membrane protein BAP31 implying cross-talk with the mitochondrial apoptosis pathway. Furthermore, we confirmed that a sustained ER stress was induced marked by an increased expression of an ER chaperone Grp78/BiP. Taken together, we have identified involvement of ER stress-mediated death program in Tula virus-infected Vero E6 cells which provides a new approach to understand the mechanisms in hantavirus-induced apoptosis.
KW - C/EBP homologous protein (Gadd153/chop)
KW - Caspase-12
KW - Endoplasmic reticulum (ER) stress
KW - Growth arrest- and DNA damage-inducible gene 153 or CAATT enhancer-binding protein
KW - Grp78/BiP
KW - Jun NH -terminal kinase (JNK)
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U2 - 10.1016/j.virol.2005.01.002
DO - 10.1016/j.virol.2005.01.002
M3 - Article
C2 - 15708603
AN - SCOPUS:13544263363
SN - 0042-6822
VL - 333
SP - 180
EP - 189
JO - Virology
JF - Virology
IS - 1
ER -