title: Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages.
abstract: Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6) MHC-I/II and B7.2 (CD86) were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.
authors.affiliation: School of Biological Sciences, National Institute of Science Education & Research, Bhubaneswar, HBNI, Jatni, Khurda, Odisha 752050, India. tapas.sbsniser@gmail.com.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Nayak
authors.affiliation: Infectious Disease Biology, Institute of Life Sciences, (Autonomous Institute of Department of Biotechnology, Government of India), Nalco Square, Bhubaneswar, Odisha 751023, India. rinku.prabhu@gmail.com.
authors.forename: Prabhudutta
authors.initials: P
authors.lastname: Mamidi
authors.affiliation: Infectious Disease Biology, Institute of Life Sciences, (Autonomous Institute of Department of Biotechnology, Government of India), Nalco Square, Bhubaneswar, Odisha 751023, India. abhishekbt13@gmail.com.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Kumar
authors.affiliation: School of Biological Sciences, National Institute of Science Education & Research, Bhubaneswar, HBNI, Jatni, Khurda, Odisha 752050, India. laishrampk@gmail.com.
authors.forename: Laishram Pradeep K
authors.initials: LP
authors.lastname: Singh
authors.affiliation: School of Biological Sciences, National Institute of Science Education & Research, Bhubaneswar, HBNI, Jatni, Khurda, Odisha 752050, India. subhransusahoo87@gmail.com.
authors.forename: Subhransu S
authors.initials: SS
authors.lastname: Sahoo
authors.affiliation: Infectious Disease Biology, Institute of Life Sciences, (Autonomous Institute of Department of Biotechnology, Government of India), Nalco Square, Bhubaneswar, Odisha 751023, India. sochat.ils@gmail.com.
authors.forename: Soma
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: School of Biological Sciences, National Institute of Science Education & Research, Bhubaneswar, HBNI, Jatni, Khurda, Odisha 752050, India. subho@niser.ac.in.
authors.forename: Subhasis
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D017209:Apoptosis; D016227:Benzoquinones / Q000378:metabolism*; D015153:Blotting, Western; D002646:Chikungunya virus / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D047029:Lactams, Macrocyclic / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000821:virology*; D051379:Mice; D000067996:RAW 264.7 Cells; D010948:Viral Plaque Assay; D014779:Virus Replication
chemical_list: D016227:Benzoquinones; D016207:Cytokines; D047029:Lactams, Macrocyclic; C112765:tanespimycin
keywords: 17-AAG; Alphavirus; Chikungunya virus; HSP90; MHC; TNF; apoptosis; macrophage