Department of Microbiology & Immunology

Columbia University Medical Center
Anne Moscona, M.D.
Professor of Pediatrics, Physiology & Cellular Biophysics and Microbiology & Immunology
M.D., Columbia University

Molecular biology of paramyxoviruses, viral entry, prevention of viral infection

Research

Our laboratory conducts basic research on paramyxoviruses that cause serious and prevalent childhood diseases, and on newly emerging paramyxoviruses that affect humans. We investigate common pediatric respiratory viruses (parainfluenza viruses, respiratory syncytial virus) as well as emerging lethal henipaviruses (Nipah and Hendra viruses). The focus is on the mechanisms of viral entry into host cells, in the intial stages of infection. The laboratory is best known for identifying critical roles of the viral receptor binding protein in activating the viral fusion process during infection. By identifying the mechanism of fusion activation, we have now have identified promising targets for interfering with the viral entry process.

The lab is organized around the interdisciplinary theme of virus-host interactions. Projects draw from strategies and methods of molecular biology, cell biology, biophysics, immunology, computational biology, structural biology, and virology. Projects are inter-related in ways that lead to constant communication and contributions to each other's development.




Selected Publications

  1. Moscona, A. (2015) RSV vaccine: Beating the virus at its own game. Sci. Transl. Med. 7: 312fs344.
  2. Mathieu, C., Huey, D., Jurgens, E., Welsch, J.C., DeVito, I., Talekar, A., Horvat, B., Niewiesk, S., Moscona, A. and Porotto, M. (2015) Prevention of measles virus infection by intranasal delivery of fusion inhibitor peptides. J. Virol. 89: 1143-1155.
  3. Gui, L., Jurgens, E.M., Ebner, J.L., Porotto, M., Moscona, A. and Lee, K.K. (2015) Electron tomography imaging of surface glycoproteins on human parainfluenza virus 3: association of receptor binding and fusion proteins before receptor engagement. MBio. 6: e02393-02314.
  4. Jurgens, E.M., Mathieu, C., Palermo, L.M., Hardie, D., Horvat, B., Moscona, A. and Porotto, M. (2015) Measles fusion machinery is dysregulated in neuropathogenic variants. MBio. 6: e02528-02514
  5. Palgen, J.L., Jurgens, E.M., Moscona, A., Porotto, M. and Palermo, L.M. (2015) Unity in diversity: shared mechanism of entry among paramyxoviruses. Prog. Mol. Biol. Transl. Sci. 129: 1-32.
  6. Palmer, S.G., DeVito, I., Jenkins, S.G., Niewiesk, S., Porotto, M. and Moscona, A. (2014) Circulating clinical strains of human parainfluenza virus reveal viral entry requirements for in vivo infection. J. Virol. 88: 13495-13502.
  7. Xu, R., Palmer, S.G., Porotto, M., Palermo, L.M., Niewiesk, S., Wilson, I.A. and Moscona, A. (2013) Interaction between the hemagglutinin-neuraminidase and fusion glycoproteins of human parainfluenza virus type III regulates viral growth in vivo. MBio. 4: e00803-00813.
  8. Welsch, J.C., Talekar, A., Mathieu, C., Pessi, A., Moscona, A., Horvat, B. and Porotto, M. (2013) Fatal measles virus infection prevented by brain-penetrant fusion inhibitors. J. Virol. 87: 13785-13794.
  9. Talekar, A., Moscona, A. and Porotto, M. (2013) Measles virus fusion machinery activated by sialic acid binding globular domain. J. Virol. 87: 13619-13627.
  10. Talekar, A., DeVito, I., Salah, Z., Palmer, S.G., Chattopadhyay, A., Rose, J.K., Xu, R., Wilson, I.A., Moscona, A. and Porotto, M. (2013) Identification of a region in the stalk domain of the nipah virus receptor binding protein that is critical for fusion activation. J. Virol. 87: 10980-10996.
  11. Porotto, M., Salah, Z.W., Gui, L., DeVito, I., Jurgens, E.M., Lu, H., Yokoyama, C.C., Palermo, L.M., Lee, K.K. and Moscona, A. (2012) Regulation of paramyxovirus fusion activation: the hemagglutinin-neuraminidase protein stabilizes the fusion protein in a pretriggered state. J. Virol. 86: 12838-12848.
  12. Pessi, A., Langella, A., Capito, E., Ghezzi, S., Vicenzi, E., Poli, G., Ketas, T., Mathieu, C., Cortese, R., Horvat, B., Moscona, A. and Porotto, M. (2012) A general strategy to endow natural fusion-protein-derived peptides with potent antiviral activity. PLoS One. 7: e36833.
  13. Talekar, A., Pessi, A., Glickman, F., Sengupta, U., Briese, T., Whitt, M.A., Mathieu, C., Horvat, B., Moscona, A. and Porotto, M. (2012) Rapid screening for entry inhibitors of highly pathogenic viruses under low-level biocontainment. PLoS One. 7: e30538.
  14. Porotto, M., Palmer, S.G., Palermo, L.M. and Moscona, A. (2012) Mechanism of fusion triggering by human parainfluenza virus type III: communication between viral glycoproteins during entry. J. Biol. Chem. 287: 778-793.
  15. Porotto, M., Devito, I., Palmer, S.G., Jurgens, E.M., Yee, J.L., Yokoyama, C.C., Pessi, A. and Moscona, A. (2011) Spring-loaded model revisited: paramyxovirus fusion requires engagement of a receptor binding protein beyond initial triggering of the fusion protein. J. Virol. 85: 12867-12880.
  16. Farzan, S.F., Palermo, L.M., Yokoyama, C.C., Orefice, G., Fornabaio, M., Sarkar, A., Kellogg, G.E., Greengard, O., Porotto, M. and Moscona, A. (2011) Premature activation of the paramyxovirus fusion protein before target cell attachment with corruption of the viral fusion machinery. J. Biol. Chem. 286: 37945-37954.
  17. Porotto, M., Yi, F., Moscona, A. and LaVan, D.A. (2011) Synthetic protocells interact with viral nanomachinery and inactivate pathogenic human virus. PLoS One. 6: e16874.
  18. Moscona, A., Porotto, M., Palmer, S., Tai, C., Aschenbrenner, L., Triana-Baltzer, G., Li, Q.X., Wurtman, D., Niewiesk, S. and Fang, F. (2010) A recombinant sialidase fusion protein effectively inhibits human parainfluenza viral infection in vitro and in vivo. J. Infect. Dis. 202: 234-241.
  19. Porotto, M., Yokoyama, C.C., Palermo, L.M., Mungall, B., Aljofan, M., Cortese, R., Pessi, A. and Moscona, A. (2010) Viral entry inhibitors targeted to the membrane site of action. J. Virol. 84: 6760-6768.
  20. Palermo, L.M., Porotto, M., Yokoyama, C.C., Palmer, S.G., Mungall, B.A., Greengard, O., Niewiesk, S. and Moscona, A. (2009) Human parainfluenza virus infection of the airway epithelium: viral hemagglutinin-neuraminidase regulates fusion protein activation and modulates infectivity. J. Virol. 83: 6900-6908.
  21. Moscona, A. (2009) Global transmission of oseltamivir-resistant influenza. N. Engl. J. Med. 360: 953-956.
  22. Aljofan, M., Porotto, M., Moscona, A. and Mungall, B.A. (2008) Development and validation of a chemiluminescent immunodetection assay amenable to high throughput screening of antiviral drugs for Nipah and Hendra virus. J. Virol. Methods. 149: 12-19.
  23. Moscona, A. and McKimm-Breschkin, J. (2007) News about influenza B drug resistance that cannot be ignored. J.A.M.A. 297: 1492-1493.
  24. Porotto, M., Doctor, L., Carta, P., Fornabaio, M., Greengard, O., Kellogg, G.E. and Moscona, A. (2006) Inhibition of hendra virus fusion. J. Virol. 80: 9837-9849.
  25. Moscona, A. (2005) Neuraminidase inhibitors for influenza. N. Engl. J. Med. 353: 1363-1373.
  26. Moscona, A. (2004) Oseltamivir-resistant influenza? Lancet. 364: 733-734.

Professor Anne Moscona
Phone: 212-305-3647
Lab Phone: 212-305-3647
Fax: 212-305-1468
Email:  am939@cumc.columbia.edu


Department of Microbiology & Immunology, Columbia University + 701 W. 168 St., HHSC 1208 New York, NY 10032 Tel. 212-305-3647