Host defense mechanism; antiviral response and inflammation: innate immune antiviral and inflammatory response against respiratory RNA viruses like human respiratory syncytial virus (RSV), and influenza A virus (flu).
Respiratory RNA virus infection and inflammation
Respiratory viruses like RSV, flu cause severe lung disease that manifest as pneumonia and bronchiolitis. These two diseases develop due to massive inflammation in the lung. Therefore, we are investigating the mechanism by which RSV and flu induce inflammation in the lung during infection. Particularly, we are interested in identifying and characterizing cellular factor that regulate inflammation. Our lab is focused on elucidating the mechanism of inflammasome activation by viruses. Inflammasome is an intracellular multi-protein complex involved in initiating inflammation by virtue of controlling production of pro-inflammatory mediators and inducing cell death. Our lab is investigating the biochemical, cellular and molecular mechanism responsible for inflammasome complex formation and activation during infection. Our studies have potential to be developed as therapeutic targets to control inflammation (and associated diseases like pneumonia) during respiratory virus infection.
Innate immune antiviral response against respiratory RNA viruses
We are studying the innate immune response (the first line of defense against pathogens) against RSV and flu. These respiratory viruses are highly pathogenic and cause diseases (pneumonia, bronchiolitis) in children/infants and elderly. We are investigating the mechanism of host derived antiviral immune response to identify novel antiviral molecules/pathways, which could be potentially developed as effective antiviral therapy or used as an immunemodulating adjuvant during vaccination. Our studies on innate immune response constitutes investigation of the role of two signaling pathways, NF-kappa B and interferon-alpa/beta induced JAK/STAT pathways in establishing an antiviral state. The long-term goal of our research is to identify and characterize a) the molecules that play a critical role in activation of these pathways and, b) the antiviral factors that are induced by NF-kappa B and JAK/STAT signaling cascades.
In summary, our laboratory encompasses several aspects of cell and molecular biology/virology with emphasis on
a) innate immune antiviral signal transduction pathway,
b) cellular/molecular mechanism that triggers inflammation during virus infection, and
c) virus-host/cell interaction.
1) Segovia, JA; Tsai, S; Chang, T; Shil, NK; Weintraub, ST; Short, JD & Bose, S. Nedd8 regulates inflammasome-dependent caspase-1 activation. Mol. Cell. Biol. 35:582-597 (2015).
2) Bose, S#; Segovia, J; Somarajan, SE; Chang, T; Kannan, TR & Baseman, JB. ADP-ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS toxin regulates inflammasome activity. MBio. 5: pii: e02186-14 (2014). # corresponding author.
3) Tsai, S; Segovia, J; Mgbemena, V; Chang, T; Berton, MT; Morris, I; Tardiff, M; Tessier, P ; Cesaro, A & Bose, S. DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway. PLoS. Pathogens. 10(1): e1003848 (2014).
Faculty of 1000 Prime selected article: evaluations for Tsai S et al PLoS. Pathogens. 10(1): e1003848 (2014). http://f1000.com/prime/718228108.
4) Thinwa, J: Segovia, JA: Bose, S & Dube, PH. Integrin-mediated pathogen recognition leads to inflammasome-dependent IL-18 secretion. J. Immunol. 193:1373-82 (2014).
5) Mgbemena, V; Segovia, J; Chang, T; Tsai, S-Y; Cole, G. T; Hung, C-Y & Bose, S. Transactivation of inducible nitric oxide synthase gene by Krüppel-like factor 6 regulates apoptosis during influenza A virus infections. J. Immunol. 189:606-615 (2012).
6) Sabbah, A; Chang, T; Harnack, R; Frohlich, V; Dube, P.H; Tominaga, K;
Xiang, Y & Bose, S. Activation of innate immune antiviral response by Nod2. Nature. Immunol. 10: 1073-1081 (2009).
“Research Highlight” article in “Nature Reviews Immunology” - Activation of innate immune antiviral responses by Nod2. Nature Reviews Immunology. 9 (12): 820 (2009).
Faculty of 1000 Prime (previously known as Faculty of 1000 Biology) selected article: evaluations for Sabbah A et al Nat Immunol 2009 Oct 10 (10):1073-80. http://www.f1000biology.com/article/id/1165583/evaluation.
Faculty of 1000 Prime - http://f1000.com/prime/1165583.
7) Segovia, J; Sabbah, A; Mgbemena, V; Tsai, S; Chang, T; Berton, M; Morris, I. R; Allen, I. C; Ting, J. P & Bose, S. TLR2/MyD88/NF-kappa B pathway, reactive oxygen species, K+ efflux activates NLRPR3/ASC inflammasome during respiratory syncytial virus infection. PLoS. One. 7:e29695 (2012).
8) Kota, S; Sabbah, A; Chang, T. H; Harnack, R; Xiang, Y; Meng, Y & Bose, S. Role of human beta-defensin-2 during tumor necrosis factor-alpha/NF-kappa B mediated innate anti-viral response against human respiratory syncytial virus. J. Biol. Chem. 283: 22417-22429 (2008).
9) Hinojosa, C.A; Mgbemena, V; Van Roekel, S; Austad, S. N; Miller, R. A; Bose, S* & Orihuela, C.J*. Enteric-delivered rapamycin enhances resistance of aged mice to pneumococcal pneumonia through reduced cellular senescence. Exp. Gerontol. 47:958-965 (2012). *Senior authors.
10) Mgbemena, V; Segovia, J; Chang, T & Bose, S. KLF6 and iNOS regulates apoptosis during respiratory syncytial virus infection. Cellular.Immunol. 283:1-7 (2013).
11) Chang, T; Segovia, J.A; Sabbah, A; Mgbemena, V & Bose, S. Role of cholesterol-rich lipid raft in human respiratory syncytial virus infection. Virology. 422: 205-211 (2012).
12) Bose, R; Thinwa, J; Chaparro, P; Zhong, Y; Bose, S; Zhong, G & Dube, P. H. MAP-kinase- dependent activation of IL-1alpha intracrine signaling is modulated by YopP during Y. enterocolitica infection. Infect. Immun. 80:289-297 (2011).
13) Echchgadda, I; Chang, T; Sabbah, A; Bakri, I; Ikeno, Y; Hubbard, G; Chatterjee, B & Bose, S. Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus: A Consequence to impaired type-I interferon-dependent antiviral response. BMC. Cancer. 11: 43 (2011).
14) Kota, S; Echchgadda, I; DeLa Cruz, I; Sabbah, A; Chang, T; Harnack, R; Mgbemena; Chatterjee, B & Bose, S. Anti-cancer oncolytic activity of respiratory syncytial virus. Cancer. Gene. Ther. 16: 923-935 (2009).
15) Bose, S; Basu, M & Banerjee, A. K. Role of nucleolin in human parainfluenza virus type 3 infection of human lung epithelial cells. J. Virol. 78: 8146-8158 (2004).
Faculty of 1000 Prime (previously known as Faculty of 1000 Biology) selected article: evaluations for Bose S et al J Virol 2004 Aug 78 (15) :8146-58. http://www.f1000biology.com/article/id/1020343/evaluation.
Faculty of 1000 Prime - http://f1000.com/prime/1020343.
16) Bose, S; Malur, A & Banerjee, A. K. Polarity of human parainfluenza virus type 3 infection in polarized human lung epithelial A549 cells : Role of microfilament and microtubule. J. Virol. 75 : 1984-1989 (2001).
17) Dong, B; Zhou, Q; Zhao, J; Zhou, A; Harty, R.N.; Bose, S; Banerjee, A; Slee, R; Guenther, J; Williams, B.R.; Wiedmer, T; Sims, P.J. & Silverman, R.H. Phospholipid scramblase 1 potentiates the antiviral activity of interferon. J. Virol. 78: 8983-8993 (2004).
Faculty of 1000 Prime (previously known as Faculty of 1000 Biology) selected article: evaluations for Dong B et al J Virol 2004 Sep 78 (17) :8983-93. http://www.f1000biology.com/article/id/1012809/evaluation.
Faculty of 1000 Prime - http://f1000.com/prime/1012809.
18) Bose, S; Kar, N; Maitra, R; Didonato, J & Banerjee, A. K. Temporal activation of NF-κB regulates an interferon independent innate anti-viral response against cytoplasmic RNA viruses. Proc. Natl. Acad. Sci. USA. 100 : 10890-10895 (2003).