Andrew Pekosz Assistant Professor Phone, office: (314)-747-2132 Phone, lab: (314)-747-2134 FAX: (314)-362-3203 email:  pekosz@borcim.wustl.edu   8230 McDonnell Pediatric Research Building Box 8230 Department of Molecular Microbiology Washington University School of Medicine 660 South Euclid Avenue St. Louis, MO 63110-1093.

Research Interests

Our long term goals are to use a combination of biochemical, molecular and genetic systems to:

1) identify and characterize the viral and cellular factors involved in infectious virus assembly.
2) utilize infectious clone technology to study the replication and pathogenesis of these viruses.
3) investigate the molecular interactions of these viruses with the host innate immune system.
4) characterize viral replication in primary respiratory epithelial cell culture systems.

One of our current projects focuses on the role of the matrix and M2 proteins of influenza A virus in virus assembly and virulence. The14C2 monoclonal antibody recognizes the extracellular portion of the influenza A virus M2 protein and is able to reduce influenza virus plaque size and infectious virus production when added to virus-infected cells. The antibody has no effect on the infectivity of cell-free virus. The majority of antibody-resistant viruses do not have changes in the antibody epitope, but possess specific amino acid changes in the cytoplasmic tail of M2, or in the matrix protein. We are currently characterizing the ability of anti-M2 antibodies to protect mice from influenza A virus challenge, assessing the virulence of the 14C2 antibody escape mutants and investigating the molecular events involved in 14C2 antibody-mediated growth restriction.

Keywords: influenza virus, RNA viruses, molecular biology and pathogenesis

CV

Publications

1. Griot, C., Pekosz, A., Lukac, D., Scherrer, S., Stillmock, K., Schmeidler, D., Endres, M., Gonzalez-Scarano, F. and Nathanson, N. (1993). Polygenic control of neuroinvasiveness in California serogroup viruses. J. Virol.  67: 3861-3867.
2. Griot, C., Pekosz, A., Davidson, R., Stillmock, K., Hock, M., Lukac, D., Schmeidler, D., Cobbinah, I., Gonzalez-Scarano, F. and Nathanson, N. (1994). Replication in cultured C2C12 muscle cells correlates with the neuroinvasiveness of California serogroup bunyaviruses. Virology 201:399-403.
3. Pekosz, A., Griot, C., Stillmock, K., Nathanson, N. and Gonzalez-Scarano, F. (1995).  Protection from La Crosse virus encephalitis with recombinant glycoproteins: role of neutralizing anti-G1 antibodies. J. Virol.  69:3475-3481.
4. Pekosz, A., Griot, C., Nathanson, N. and Gonzalez-Scarano, F. (1995). Tropism of bunyaviruses: evidence for a G1 glycoprotein mediated entry pathway common to the California serogroup. Virology 214:339-348.
5. Griot, C., Pekosz, A., Davidson, R., Nathanson, N., and Gonzalez-Scarano, F. (1995). Replication of California serogroup viruses in differentiated C2C12 muscle cells; a novel in vitro model for neuroinvasiveness. Immunobiology of Viral Infections.: Proc. from the 3rd Congress Europ. Soc. Vet. Virol.  Schwyzer, M., Ackerman, M. et al. Eds., pp. 59-62
6. Pekosz, A., Phillips, J., Pleasure, D., Merry, D. and Gonzalez-Scarano, F. (1996). Inhibition of La Crosse virus induced apoptosis in a human neuronal cell line by overexpression of bcl-2. J. Virol. 70: 5329-5335.
7. Pekosz, A. and Gonzalez-Scarano, F. (1996). The extracellular domain of La Crosse virus G1 forms oligomers and undergoes pH-dependent conformational changes. Virology 225:243-247.
8. Tatarowicz, W., Martin, C. E., Pekosz, A., Madden, S. L., Rauscher, F. J., Chiang, S.-U., Beerman, T. A. and Fraser, N. W. (1997). Repression of the HSV-1 latency-associated transcript [LAT] promoter by early growth response [EGR] proteins: involvement of a binding site immediately downstream of the TATA box. J. Neurovirol. 3:212-224.
9. Pekosz, A. and Lamb, R. A. (1997). The CM2 protein of influenza C virus is an oligomeric integral membrane glycoprotein structurally analogous to influenza A virus M2 and influenza B virus NB proteins. Virology 237: 439-451.
10. Pekosz, A. and Lamb, R. A. (1998).  Influenza C virus CM2 integral membrane glycoprotein is produced from a polypeptide precursor by cleavage of an internal signal sequence. Proc. Natl. Acad. Sci. USA 95:13233-13238.
11. Pekosz, A., He, B. and Lamb, R. A. (1999). Reverse genetics of negative-strand RNA viruses: Closing the circle. Proc. Natl. Acad. Sci. USA 96:8804-8806.
12. Pekosz, A. and Lamb, R. A. (1999). Cell surface expression of biologically active Influenza C virus HEF glycoprotein expressed from cDNA. J. Virol. 73:8808-8812.
13. Mould, J. A., Li, H.-C., Dudlak, C. S., Pekosz, A., Lear, J. D., Lamb, R. A. and Pinto, L. H. (2000). Mechanism for proton conductance of the M2 ion channel of influenza A virus. J. Biol. Chem. 275:8592-8599.
14. Zhang, J., Leser, G. P., Pekosz, A. and Lamb, R. A. (2000). The cytoplasmic tails of the influenza virus spike glycoproteins are required for normal genome packaging. Virology 269:325-334.
15. Zhang, J., Pekosz, A. and Lamb, R. A. (2000). Influenza virus assembly and lipid raft microdomains: A role for the cytoplasmic tails of the spike glycoproteins. J. Virol., 74:4634-4644.
16. Mould, J. A., Drury, J. E., Frings, S. M., Kaupp, U. B., Pekosz, A., Lamb, R. A. and Pinto, L. H. (2000). Permeation and activation of the M2 ion channel of influenza A virus.  J. Biol. Chem. 275:31038-31050.
17. Pekosz, A. and Lamb, R. A. (2000). Identification of a membrane targeting and degradation signal in the p42 protein of influenza C virus. J. Virol. 74:10480-10488.
18. Takeda, M., Pekosz, A., Shuck, K., Pinto, L. H. and Lamb, R.A. (2002). Influenza A virus M2 ion channel is essential for efficient replication in tissue culture. J. Virol. 76:1391-1399.19. 
    
19. Krug, A., Veeraswamy, R., Pekosz, A., Kanagawa, O., Unanue, E.R., Colonna, M., and Cella, M. (2003). Interferon-producing cells fail to initiate immune responses but induce strong Th1 differentiation of antigen-experienced uncommitted T cells
20. McCown, M., Diamond, M. S. and Pekosz, A. (2003).   Small interfering RNAs block gene expression and virus production of negative and positive strand RNA viruses. Virology. 313:514-24.
    

 
 

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WWW www@borcim.wustl.edu Department of Molecular Microbiology, Box 8230 Washington University School of Medicine St. Louis, MO 63110-1093 USA

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