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

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

Anne Moscona, M.D.

Sherie L. Morrison Professor of Immunology (in Microbiology & Immunology), Pediatrics and Physiology & Cellular Biophysics
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.

Professor Moscona is a Fellow of the American Academy of Microbiology.

 

Selected Publications

  1. Marcink, T.C., Zipursky, G., Cheng, W., Stearns, K., Stenglein, S., Golub, K., Cohen, F., Bovier, F., Pfalmer, D., Greninger, A.L., Porotto, M., des Georges, A. and Moscona, A. (2023) Subnanometer structure of an enveloped virus fusion complex on viral surface reveals new entry mechanisms. Science Adv. 9: eade2727. https://doi.org/10.1126/sciadv.ade2727

  2. Reynard, O., Gonzalez, C., Dumont, C., Iampietro, M., Ferren, M., Le Guellec, S., Laurie, L., Mathieu, C., Carpentier, G., Roseau, G., Bovier, F.T., Zhu, Y., Le Pennec, D., Montharu, J., Addetia, A., Greninger, A.L., Alabi, C.A., Brisebard, E., Moscona, A., Vecellio, L., Porotto, M. and Horvat, B. (2022) Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection. Nature Commun. 13: 6439. https://doi.org/10.1038/s41467-022-33832-6

  3. de Vries, R. D., Schmitz, K.S., Bovier, F.T., Predella, C., Khao, J., Noack, D., Haagmans, B. L., Herfst, S., Stearns, K.N., Drew-Bear, J., Biswas, S., Rockx, B., McGill, G., Dorrello, N.V., Gellman, S.H., Alabi, C. A., de Swart, R. L., Moscona, A. and Porotto, M. (2021) Intranasal fusion inhibitory lipopeptide prevents direct-contact SARS-CoV-2 transmission in ferrets. Science 371: 1379–1382. https://doi.org/10.1126/science.abf4896

  4. Rijsbergen, L.C., Schmitz, K.S., Begeman, L., Drew-Bear, J., Gommers, L., Lamers, M.M., Greninger, A. L., Haagmans, B.L., Porotto, M., de Swart, R. L., Moscona, A. and de Vries, R.D. (2021) Modeling infection and tropism of human parainfluenza virus type 3 in ferrets. mBio 13: e0383121. https://doi.org/10.1128/mbio.03831-21

  5. Ferren, M., Favède, V., Decimo, D., Iampietro, M., Lieberman, N. A. P., Weickert, J.L., Pelissier, R., Mazelier, M., Terrier, O., Moscona, A., Porotto, M., Greninger, A. L., Messaddeq, N., Horvat, B. and Mathieu, C. (2021) Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection. Nature Commun. 12: 5809. https://doi.org/10.1038/s41467-021-26096-z

  6. Greninger, A.L., Rybkina, K., Lin, M.J., Drew-Bear, J., Marcink, T.C., Shean, R. C., Makhsous, N., Boeckh, M., Harder, O., Bovier, F., Burstein, S.R., Niewiesk, S., Rima, B.K., Porotto, M. and Moscona, A. (2021) Human parainfluenza virus evolution during lung infection of immunocompromised individuals promotes viral persistence. J. Clin. Invest. 131: e150506. https://doi.org/10.1172/JCI150506

  7. Outlaw, V.K., Cheloha, R.W., Jurgens, E.M., Bovier, F.T., Zhu, Y., Kreitler, D.F., Harder, O., Niewiesk, S., Porotto, M., Gellman, S. H. and Moscona, A. (2021) Engineering protease-resistant peptides to inhibit human parainfluenza viral respiratory infection. J. Am. Chem. Soc. 143: 5958–5966. https://doi.org/10.1021/jacs.1c01565

  8. Rodrigues Toste de Carvalho, A.L., Liu, H.Y., Chen, Y.W., Porotto, M., Moscona, A. and Snoeck, H.W. (2021). The in vitro multilineage differentiation and maturation of lung and airway cells from human pluripotent stem cell-derived lung progenitors in 3D. Nature Protoc. 16: 1802–1829. https://doi.org/10.1038/s41596-020-00476-z

  9. Marcink, T. C., Wang, T., des Georges, A., Porotto, M., & Moscona, A. (2020). Human parainfluenza virus fusion complex glycoproteins imaged in action on authentic viral surfaces. PLoS Pathog. 16: e1008883. https://doi.org/10.1371/journal.ppat.1008883

  10. Outlaw, V.K., Bovier, F.T., Mears, M.C., Cajimat, M.N., Zhu, Y., Lin, M.J., Addetia, A., Lieberman, N.A.P., Peddu, V., Xie, X., Shi, P.Y., Greninger, A.L., Gellman, S.H., Bente, D.A., Moscona, A. and Porotto, M. (2020) Inhibition of coronavirus entry in vitro and ex vivo by a lipid-conjugated peptide derived from the SARS-CoV-2 spike glycoprotein HRC domain. mBio 11: e01935-20. https://doi.org/10.1128/mBio.01935-20 [Editor’s Pick]

  11. Porotto, M., Ferren, M., Chen, Y.W., Siu, Y., Makhsous, N., Rima, B., Briese, T., Greninger, A.L., Snoeck, H.W. and Moscona, A. (2019) Authentic modeling of human respiratory virus infection in human pluripotent stem cell-derived lung organoids. mBio 10: e00723-19. https://doi.org/10.1128/mBio.00723-19

  12. Mathieu, C., Porotto, M., Figueira, T.N., Horvat, B. and Moscona, A. (2018) Fusion inhibitory lipopeptides engineered for prophylaxis of Nipah virus in primates. J. Infect Dis. 218: 218-227.

  13. Iketani, S., Shean, R.C., Ferren, M., Makhsous, N., Aquino, D.B., des Georges, A., Rima, B., Mathieu, C., Porotto, M., Moscona, A. and Greninger, A.L. (2018) Viral entry properties required for fitness in humans are lost through rapid genomic change during viral isolation. mBio 9: e00898-18.

  14. Augusto, M.T., Hollmann, A., Porotto, M., Moscona, A. and Santos, N.C. (2017) Antiviral lipopeptide-cell membrane interaction is influenced by PEG linker length. Molecules doi:10.3390/molecules22071190.

  15. Chen, Y.W., Huang, S.X., de Carvalho, A.L.R.T., Ho, S.H., Islam, M.N., Volpi, S., Notarangelo, L.D., Ciancanelli, M., Casanova, J.L., Bhattacharya, J., Liang, A.F., Palermo, L.M., Porotto, M., Moscona, A. and Snoeck, H.W. (2017) A three-dimensional model of human lung development and disease from pluripotent stem cells. Nature Cell Biol. 19: 542-549.

  16. Figueira, T.N., Freire, J.M., Cunha-Santos, C., Heras, M., Gonçalves, J., Moscona, A., Porotto, M., Salomé Veiga, A. and Castanho, M.A. (2017) Quantitative analysis of molecular partition towards lipid membranes using surface plasmon resonance. Sci. Rep. 7: 45647.

  17. Mathieu, C., Augusto, M.T., Niewiesk, S., Horvat, B., Palermo, L.M., Sanna, G., Madeddu, S., Huey, D., Castanho, M.A., Porotto, M., Santos, N.C. and Moscona, A. (2017) Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides. Sci. Rep. 7: 43610.

  18. Figueira, T.N., Palermo, L.M., Veiga, A.S., Huey, D., Alabi, C.A., Santos, N.C., Welsch, J.C., Mathieu, C., Horvat, B., Niewiesk, S., Moscona, A., Castanho, M.A. and Porotto, M. (2016) In vivo efficacy of measles virus fusion protein-derived peptides is modulated by the properties of self-assembly and membrane residence. J. Virol. pii: e01554-16.

  19. Moscona, A. (2015) RSV vaccine: Beating the virus at its own game. Sci. Transl. Med. 7: 312fs344.

  20. 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.

  21. 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.

  22. 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

  23. 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.

  24. 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.

  25. 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.

  26. 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.

  27. Talekar, A., Moscona, A. and Porotto, M. (2013) Measles virus fusion machinery activated by sialic acid binding globular domain. J. Virol. 87: 13619-13627.

  28. 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.

  29. 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.

  30. 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.

  31. 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.

  32. 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.

  33. 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.

  34. 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.

  35. 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.

  36. 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.

  37. 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.

  38. 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.

  39. Moscona, A. (2009) Global transmission of oseltamivir-resistant influenza. N. Engl. J. Med.360: 953-956.

  40. 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.

  41. Moscona, A. and McKimm-Breschkin, J. (2007) News about influenza B drug resistance that cannot be ignored. J.A.M.A. 297: 1492-1493.

  42. 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.

  43. Moscona, A. (2005) Neuraminidase inhibitors for influenza. N. Engl. J. Med. 353: 1363-1373.

  44. Moscona, A. (2004) Oseltamivir-resistant influenza? Lancet. 364: 733-734.