Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappaB activation.
Severe acute respiratory syndrome (SARS) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ARDS) associated with uncontrolled inflammatory responses. Here, we demonstrated that, among five accessory proteins of SARS coronavirus (SARS-CoV) tested, 3a/X1 and 7a/X4 were capable of activating nuclear factor kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK), and significantly enhanced interleukin 8 (IL-8) promoter activity. Furthermore, 3a/X1 and 7a/X4 expression in A549 cells enhanced production of inflammatory chemokines that were known to be up-regulated in SARS-CoV infection. Our results suggest potential involvement of 3a/X1 and 7a/X4 proteins in the pathological inflammatory responses in SARS.
Kanzawa
Noriyuki
N
Department of Immunotherapeutics, Tokyo Medical and Dental University, Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Nishigaki
Kazuo
K
Hayashi
Takaya
T
Ishii
Yuichi
Y
Furukawa
Souichi
S
Niiro
Ayako
A
Yasui
Fumihiko
F
Kohara
Michinori
M
Morita
Kouichi
K
Matsushima
Kouji
K
Le
Mai Quynh
MQ
Masuda
Takao
T
Kannagi
Mari
M
D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis*; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
D018925:Chemokines; D048031:JNK Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D015678:Viral Structural Proteins; C515313:ORF3A protein, SARS coronavirus; D000086082:Viroporin Proteins; C488151:sars7a protein, SARS virus