Joseph Ashour, PhD
- ASSISTANT PROFESSOR | Microbiology
Notwithstanding their antigen specificity, B cells display characteristics of an innate response as well, though their role in the innate response to virus infection has been largely overlooked due to their paucity in vivo. This may be a regrettable omission, given that many infections are recurrent episodes, including those caused by dengue virus (DENV) and influenza virus (IAV) where antigen-specific B-cells are present a priori. Antigen-specific B-cells remain at the site of infection long after the infection has been cleared. Such B-cells express a high affinity pathogen-specific receptor, the BCR, which, upon stimulation, can synergize with the TLR signaling pathway leading to a stronger transcriptional response. In accordance with this, exposure to interferon results in increased TLR7 expression, lowered thresholds for BCR activation and increased cytokine production. Thus for many viral infections, the sentinel role of plasmacytoid dendritic cells (pDCs) might be complemented by antigen-specific B-cells.
The primary focus of the Ashour lab is examining the contribution of antigen-specific B cells to the innate immune response against virus. The tools we use to accomplish this include 1) somatic cell nuclear transfer derived antigen specific B-cells 2) heavy domain of heavy-chain only antibodies isolated from alpacas (nanobodies) and 3) sortase based chemo-enzymatic labeling of host and virus proteins. By combining these cutting edge technologies with conventional biochemistry and cell biology we hope to expand our knowledge in the frontier of virus-B-cell interactions.
Multi-Disciplinary Training AreaMicrobiology [MIC]
PhD, Mount Sinai School of Medicine Graduate School of Biological Sciences
Whitehead Institute for Biomedical Research at MIT
Dougan SK, Ashour J, Karssemeijer RA, Popp MW, Avalos AM, Barisa M, Altenburg AF, Ingram JR, Cragnolini JJ, Guo C, Alt FW, Jaenisch R, Ploegh HL. Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus. Nature 2013 Nov; 503(7476).
Sanyal S, Ashour J, Maruyama T, Altenburg AF, Cragnolini JJ, Bilate A, Avalos AM, Kundrat L, García-Sastre A, Ploegh HL. Type I interferon imposes a TSG101/ISG15 checkpoint at the Golgi for glycoprotein trafficking during influenza virus infection. Cell host & microbe 2013 Nov; 14(5).
Tafesse FG, Sanyal S, Ashour J, Guimaraes CP, Hermansson M, Somerharju P, Ploegh HL. Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of influenza virus glycoproteins. Proceedings of the National Academy of Sciences of the United States of America 2013 Apr; 110(16).
Hendricks GL, Weirich KL, Viswanathan K, Li J, Shriver ZH, Ashour J, Ploegh HL, Kurt-Jones EA, Fygenson DK, Finberg RW, Comolli JC, Wang JP. Sialylneolacto-N-tetraose c (LSTc)-bearing liposomal decoys capture influenza A virus. The Journal of biological chemistry 2013 Mar; 288(12).
Ashour J, Morrison J, Laurent-Rolle M, Belicha-Villanueva A, Plumlee CR, Bernal-Rubio D, Williams KL, Harris E, Fernandez-Sesma A, Schindler C, García-Sastre A. Mouse STAT2 restricts early dengue virus replication. Cell host & microbe 2010 Nov; 8(5).
Rodriguez-Madoz JR, Belicha-Villanueva A, Bernal-Rubio D, Ashour J, Ayllon J, Fernandez-Sesma A. Inhibition of the type I interferon response in human dendritic cells by dengue virus infection requires a catalytically active NS2B3 complex. Journal of virology 2010 Oct; 84(19).
Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, García-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. Journal of virology 2010 Apr; 84(7).
Ashour J, Laurent-Rolle M, Shi PY, García-Sastre A. NS5 of dengue virus mediates STAT2 binding and degradation. Journal of virology 2009 Jun; 83(11).
Muñoz-Fontela C, Macip S, Martínez-Sobrido L, Brown L, Ashour J, García-Sastre A, Lee SW, Aaronson SA. Transcriptional role of p53 in interferon-mediated antiviral immunity. The Journal of experimental medicine 2008 Aug; 205(8).
Muñoz-Jordán JL, Laurent-Rolle M, Ashour J, Martínez-Sobrido L, Ashok M, Lipkin WI, García-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. Journal of virology 2005 Jul; 79(13).
Ashour J, Hondalus MK. Phenotypic mutants of the intracellular actinomycete Rhodococcus equi created by in vivo Himar1 transposon mutagenesis. Journal of bacteriology 2003 Apr; 185(8).