Tyrosine phosphorylation modulates mitochondrial chaperonin Hsp60 and delays rotavirus NSP4-mediated apoptotic signaling in host cells.
Phosphoproteomics-based platforms have been widely used to identify post translational dynamics of cellular proteins in response to viral infection. The present study was undertaken to assess differential tyrosine phosphorylation during early hours of rotavirus (RV) SA11 infection. Heat shock proteins (Hsp60) were found to be enriched in the data set of RV-SA11 induced differentially tyrosine-phosphorylated proteins at 2 hr post infection (hpi). Hsp60 was further found to be phosphorylated by an activated form of Src kinase on 227th tyrosine residue, and tyrosine phosphorylation of mitochondrial chaperonin Hsp60 correlated with its proteasomal degradation at 2-2.5hpi. Interestingly, mitochondrial Hsp60 positively influenced translocation of the rotaviral nonstructural protein 4 to mitochondria during RV infections. Phosphorylation and subsequent transient degradation of mitochondrial Hsp60 during early hours of RV-SA11 infection resulted in inhibition of premature import of nonstructural protein 4 into mitochondria, thereby delaying early apoptosis. Overall, the study highlighted one of the many strategies rotavirus undertakes to prevent early apoptosis and subsequent reduced viral progeny yield.
Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road SchemeP- XM, Beliaghata, Kolkata, 700010, India.
Shiladitya
S
Chattopadhyay
Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road SchemeP- XM, Beliaghata, Kolkata, 700010, India.
Arpita
A
Mukherjee
Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road SchemeP- XM, Beliaghata, Kolkata, 700010, India.
Upayan
U
Patra
Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road SchemeP- XM, Beliaghata, Kolkata, 700010, India.
Rahul
R
Bhowmick
Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110020, India.|Academy of Scientific and Innovative Research (AcSIR), CSIR-IGIB campus, New Delhi, India.
Trayambak
T
Basak
Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110020, India.|Academy of Scientific and Innovative Research (AcSIR), CSIR-IGIB campus, New Delhi, India.
Shantanu
S
Sengupta
Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road SchemeP- XM, Beliaghata, Kolkata, 700010, India.
Mamta
M
Chawla-Sarkar
D017209:Apoptosis; D002460:Cell Line; D018834:Chaperonin 60 / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D012401:Rotavirus / Q000472:pathogenicity*; D015398:Signal Transduction; D013997:Time Factors; D014118:Toxins, Biological / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
D018834:Chaperonin 60; D006023:Glycoproteins; C081369:NS28 protein, rotavirus; D014118:Toxins, Biological; D017361:Viral Nonstructural Proteins; D014443:Tyrosine; D046988:Proteasome Endopeptidase Complex