The molecular chaperone heat shock protein-90 positively regulates rotavirus infectionx.
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 NFkappaB 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.
Dutta
Dipanjan
D
Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme-XM, Beliaghata, Kolkata-700010, West Bengal, India.
Bagchi
Parikshit
P
Chatterjee
Arunachal
A
Nayak
Mukti Kant
MK
Mukherjee
Anupam
A
Chattopadhyay
Shiladitya
S
Nagashima
Shigeo
S
Kobayashi
Nobumichi
N
Komoto
Satoshi
S
Taniguchi
Koki
K
Chawla-Sarkar
Mamta
M
D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling; D005814:Genes, Viral; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology*; D000882:Haplorhini; D054884:Host-Pathogen Interactions; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D012401:Rotavirus / Q000502:physiology*; D010948:Viral Plaque Assay / Q000379:methods; D014779:Virus Replication
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C112765:tanespimycin