TY - JOUR
T1 - The molecular chaperone heat shock protein-90 positively regulates rotavirus infectionx
AU - Dutta, Dipanjan
AU - Bagchi, Parikshit
AU - Chatterjee, Arunachal
AU - Nayak, Mukti Kant
AU - Mukherjee, Anupam
AU - Chattopadhyay, Shiladitya
AU - Nagashima, Shigeo
AU - Kobayashi, Nobumichi
AU - Komoto, Satoshi
AU - Taniguchi, Koki
AU - Chawla-Sarkar, Mamta
N1 - Funding Information:
The study was supported by financial assistance from the Indian Council of Medical Research (ICMR), New Delhi and the Program of founding research centers for emerging and reemerging infectious diseases (Okayama University-NICED, India) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. D. Dutta, A. Mukherjee and M.K. Nayak are supported by the Senior Research Fellowship from UGC, Govt. of India.
PY - 2009/9/1
Y1 - 2009/9/1
N2 - Rotaviruses are the major cause of severe dehydrating gastroenteritis in children worldwide. In this study, we report a positive role of cellular chaperone Hsp90 during rotavirus infection. A highly specific Hsp90 inhibitor, 17-allylamono-demethoxygeldanamycin (17-AAG) was used to delineate the functional role of Hsp90. In MA104 cells treated with 17-AAG after viral adsorption, replication of simian (SA11) or human (KU) strains was attenuated as assessed by quantitating both plaque forming units and expression of viral genes. Phosphorylation of Akt and NFκB observed 2-4 hpi with SA11, was strongly inhibited in the presence of 17-AAG. Direct Hsp90-Akt interaction in virus infected cells was also reduced in the presence of 17-AAG. Anti-rotaviral effects of 17-AAG were due to inhibition of activation of Akt that was confirmed since, PI3K/Akt inhibitors attenuated rotavirus growth significantly. Thus, Hsp90 regulates rotavirus by modulating cellular signaling proteins. The results highlight the importance of cellular proteins during rotavirus infection and the possibility of targeting cellular chaperones for developing new anti-rotaviral strategies.
AB - Rotaviruses are the major cause of severe dehydrating gastroenteritis in children worldwide. In this study, we report a positive role of cellular chaperone Hsp90 during rotavirus infection. A highly specific Hsp90 inhibitor, 17-allylamono-demethoxygeldanamycin (17-AAG) was used to delineate the functional role of Hsp90. In MA104 cells treated with 17-AAG after viral adsorption, replication of simian (SA11) or human (KU) strains was attenuated as assessed by quantitating both plaque forming units and expression of viral genes. Phosphorylation of Akt and NFκB observed 2-4 hpi with SA11, was strongly inhibited in the presence of 17-AAG. Direct Hsp90-Akt interaction in virus infected cells was also reduced in the presence of 17-AAG. Anti-rotaviral effects of 17-AAG were due to inhibition of activation of Akt that was confirmed since, PI3K/Akt inhibitors attenuated rotavirus growth significantly. Thus, Hsp90 regulates rotavirus by modulating cellular signaling proteins. The results highlight the importance of cellular proteins during rotavirus infection and the possibility of targeting cellular chaperones for developing new anti-rotaviral strategies.
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U2 - 10.1016/j.virol.2009.06.044
DO - 10.1016/j.virol.2009.06.044
M3 - Article
C2 - 19628238
AN - SCOPUS:68749118090
SN - 0042-6822
VL - 391
SP - 325
EP - 333
JO - Virology
JF - Virology
IS - 2
ER -