The apoptotic capability of coxsackievirus B3 is influenced by the efficient interaction between the capsid protein VP2 and the proapoptotic host protein Siva.
Infections with coxsackievirus B3 (CVB3) are common causes of myocarditis in humans. One detail of CVB3-induced pathogenesis is apoptosis. The interaction between the capsid protein VP2 of the myocardial virus variant CVB3H3 and the proapoptotic host cell protein Siva has recently been observed. In order to characterize the interaction between both proteins more precisely, the binding activity of the CVB3H3 VP2 to Siva was compared to that of the mutant virus CVB3H310A1 VP2. We found that the asparagine at position 165 in VP2 is essential for a stable interaction with Siva influencing also the induction of apoptosis, viral spread, and inflammatory responses in vivo. Furthermore, the specific binding site of Siva to VP2 is located at amino acid positions 118-136. Together, these results show that the interaction between VP2 of CVB3H3 and Siva is a highly specific process involving distinct amino acids on both proteins that most likely influence the outcome of CVB3-caused disease.
Henke
A
A
Institute of Virology, Medical Center, Friedrich Schiller University Jena, Winzerlaer Strasse 10, D-07745 Jena, Germany. i6hean@rz.uni-jena.de
Nestler
M
M
Strunze
S
S
Saluz
H P
HP
Hortschansky
P
P
Menzel
B
B
Martin
U
U
Zell
R
R
Stelzner
A
A
Munder
T
T
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D002213:Capsid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D036022:Capsid Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029822:Enterovirus B, Human / Q000472:pathogenicity* / Q000502:physiology; D004769:Enterovirus Infections / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010179:Pancreas / Q000473:pathology / Q000821:virology; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D014158:Transcription, Genetic
D051017:Apoptosis Regulatory Proteins; D036022:Capsid Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012367:RNA, Viral; C484569:Siva protein, mouse; C442554:VP2 protein, Echovirus