Alsharifi, Mohammed - University of Adelaide - School of Biological Sciences

研究领域

I. Cross-Protective influenza vaccine. Protection against re-infection with homotypic influenza virus is mediated primarily by neutralizing antibodies but recovery from newly arisen influenza virus infections requires cytotoxic CD8+ T (Tc) cells. While neutralizing antibodies target mainly the viral surface glycoproteins (HA and NA), which are subject to frequent antigenic variation, influenza-immune Tc cells target the more conserved proteins, such as the viral nucleoprotein (NP) and matrix protein. Accordingly, any universal influenza vaccine should have the capability of inducing cross-protective Tc cell responses. We have reported that gamma-irradiated influenza A virus preparations can induce cross-reactive Tc cell responses and shown that a single intranasal administration of g-H1N1 protects mice against lethal avian H5N1 and other heterotypic influenza A infections. potential projects for postgraduate research students would be in the areas of: 1. Cross-protective cytotoxic T cell responses induced by g-flu. 2. The role of the cytolytic effector molecules in recovery from influenza infection. 3. Cross-protective antibody responses induced by g-flu. 4. Recognition of g-flu and the induction of cross-protective immunity. II. Exhaustion of IFN-I response and the susceptibility to secondary infections. We have previously reported that type I interferon (IFN-I) response mediates systemic, partial lymphocyte activation which is evident by elevated expression of CD69 and CD86. Using avirulent strain of Semliki Forest Virus (SFV) as a model, we have found that induction of both IFN-I response and the associated lymphocyte activation to be dependent on virus viability as γ-irradiated SFV (γ-SFV) failed to induce either. We have also reported a period of exhausted IFN-I responses as a result of primary viral infections, which was associated with enhanced susceptibility to a secondary infection with an unrelated virus. Our aim is to investigate the underlying factors responsible for the deficiency in IFN-I responses following acute viral infections, and to address some therapeutic approaches to alleviate the period of the enhanced susceptibility. Interestingly, we found γ-irradiation of influenza virus, in contrast to that of SFV, did not abrogate the induction of IFN-I. Thus, IFN-I responses of two unrelated ssRNA viruses and their γ-irradiated counterparts will be investigated to establish a model to study the underlying factors responsible for the deficiency in IFN-I responses. potential projects for postgraduate research students would be in the areas of: 1. Induction of IFN-I responses by SFV and Flu and their g-irradiated counterparts. 2. The consequences of the sub-optimal response to secondary viral infections. 3. The underlying factors for the deficient IFN-I response following an acute viral infection. 4. Possible therapeutic approaches to alleviate the enhanced susceptibility to secondary infections.

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Mohammed Alsharifi, Mario Lobigs, Matthias Regner, Eva Lee, Aulikki Koskinen, Arno Müllbacher. Type-I interferons, in response to viral infection, trigger systemic, partial, lymphocyte activation. The Journal of Immunology, 2005; 175: 4635-4640. David B. Rosen, Jayaram Bettadapura, Mohammed Alsharifi, Porunelloor A. Mathew, Hilary S. Warren, and Lewis L. Lanier. CUTTING EDGE: Lectin-like transcript-1 (LLT1) is a ligand for the inhibitory human NKR-P1A receptor. The Journal of Immunology, 2005; 176:7796-7799. Mohammed Alsharifi, Mario Lobigs, Markus M. Simon, Astrid Kersten, Klaus Müller, Aulikki Koskinen, Eva Lee and Arno Müllbacher. NK cells mediated immunopathology during an acute viral infection of the CNS. The European Journal of Immunology, 2006; 36:887-96. Arno Müllbacher, Mario Lobigs, Mohammed Alsharifi and Matthias Regner. A new look at cytotoxic T cell immunity as target for an influenza vaccine is warranted. The Lancet Infectious Diseases, 2006; 6: 255-256. Mohammed Alsharifi, Mario Lobigs, Robert Blanden, Matthias Regner, Eva Lee, Aulikki Koskinen, Arno Müllbacher. Exhaustion of type-I Interferon following an acute viral infection. The Journal of Immunology, 2006; 177: 3235–3241. Alison Budd, Lisa Alleva, Mohammed Alsharifi, Aulikki Koskinen, Victoria Smyth, Arno Müllbacher, Jeff Wood, Ian Clark. Increased Survival after Gemfibrozil Treatment of Severe Murine Influenza. Antimicrobial Agents and Chemotherapy, 2007; 51:2965-2968. Mohammed Alsharifi, Arno Müllbacher, Matthias Regner. Interferon Type-I responses in Primary and Secondary Infections. Immunology and Cell Biology, 2008; 86: 239-245. Mohammed Alsharifi, Mario Lobigs, Jayaram Bettadapura, Aulikki Koskinen, Arno Müllbacher. Restrict alphavirus replication in perforin and Fas-L double deficient mice. Journal of General Virology, 2008; 89:1942-1944. Mario Lobigs, Maximilian Larena, Mohammed Alsharifi, Eva Lee and Megan Pavy. Live chimeric and inactivated Japanese encephalitis virus vaccines differ in their cross-protective value against Murray Valley encephalitis virus. Journal of Virology. 2009;83(6):2436-45. Epub 2008 Dec 24. Mohammed Alsharifi, Yoichi Furuya, Timothy R. Bowden, Mario Lobigs, Aulikki Koskinen, Matthias Regner, Lee Trinidad, David B. Boyle and Arno Müllbacher. Intranasal flu vaccine protective against seasonal and H5N1 avian influenza infections. PLoS ONE. 2009;4(4):e5336. Epub 2009 Apr 29.