Matteo Porotto, Ph.D.

Associate Professor of Viral Molecular Pathogenesis (in Pediatrics)
Ph.D., Università degli Studi di Genova

Mechanism of measles CNS adaptation, viral fusion, antiviral approaches

Research
The overall goal of our research is to understand the steps in the entry of enveloped viruses into their target cells, as the first step in infection. The focus has been on a group of paramyxoviruses that includes pediatric respiratory pathogens as well as emerging lethal viruses. The fundamental aspects of this research have identified key roles of viral glycoproteins during the receptor binding and entry process, and most recently of the interactions between the two surface glycoproteins during their mediation of membrane fusion. These fundamental findings have led, in the last 5 years, to our design of novel antiviral strategies that target each of the steps in entry. These antiviral approaches, in turn, have yielded valuable tools and reagents for furthering our understanding of basic mechanisms. Current projects in our group include ongoing in-depth basic research on the mechanisms of virus-induced membrane fusion, with a major focus on pathogenesis of measles virus. The applications of our findings to preventing infection include not only measles virus, but also parainfluenza viruses, influenza viruses, and other emerging lethal viruses (e.g. Ebola virus).

Selected Publications

1. Figueira TN, Palermo LM, Veiga AS, Huey D, Alabi CA, Santos NC, Welsch JC, Mathieu C, Horvat B, Niewiesk S, Moscona A, Castanho MA, Porotto M. (2016) In vivo efficacy of measles virus fusion protein-derived peptides is modulated by properties of self-assembly and membrane residence. J Virol. 91. pii: JVI.01554-16.

2. Gui L, Jurgens EM, Ebner J, Porotto M*, Moscona A*, Lee KK*. (2015) Electron tomography imaging of surface glycoproteins on human parainfluenza virus 3: Association of receptor binding and fusion proteins before receptor engagement. MBio. 6. pii: e02393-14. doi: 10.1128/mBio.02393-14. PMID: 25670774 *Co-corresponding

3. Jurgens EM, Mathieu C, Palermo LM, Hardie D, Horvat B, Moscona A, Porotto M. (2015) Measles fusion machinery is dysregulated in neuropathogenic variants. MBio. 6. pii: e02528-14. doi: 10.1128/mBio.02528-14. PMID: 25670774

4. Mathieu C., Huey D., Jurgens E., Welsch J.C., Talekar A., Horvat B., Niewiesk S., Moscona A., Porotto M. (2015) Prevention of measles infection by intranasal delivery of fusion inhibitor peptides. J Virol. 89: 1143-1155. doi: 10.1128/JVI.02417-14. Epub 2014 Nov 5. PMID: 25378493

5. *Welsch JC, Talekar A, Mathieu C, Pessi A, Moscona A, Horvat B, Porotto M. (2013) Fatal measles infection prevented by brain-penetrant fusion inhibitors. J Virol. 87: 13785-13794. doi: 10.1128/JVI.02436-13. Epub 2013 Oct 9. PMID: 24109233

6. Talekar A, Moscona A, Porotto M. (2013) Measles fusion machinery activated by sialic acid binding globular domain. J Virol. 87: 13619-13627. doi: 10.1128/JVI.02256-13. Epub 2013 Oct 9. PMID: 24109225

7. Talekar A, Devito I, Salah Z, Palmer SG, Chattopadhyay A, Rose JK, Xu R, Wilson IA, Moscona A, 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. doi: 10.1128/JVI.01646-13. Epub 2013 Jul 31. PMID: 23903846

8. Porotto M, Salah Z, Long G, De Vito I, Jurgens EM, Yokoyama CC, Palermo LM, Lee KK, Moscona A. Regulation of paramyxovirus fusion activation: the hemagglutinin-neuraminidase protein stabilizes the fusion protein in a pre triggered state. J Virol. 2012 Dec;86(23):12838-48. doi: 10.1128/JVI.01965-12. Epub 2012 Sep 19. PMID: 22993149

9. *Pessi A, Langella A, Capitò E, Ghezzi S, Vicenzi E, Mathieu C, Poli G, Ketas T, Cortese R, Horvat B, Moscona A and Porotto M. General strategy to endow natural fusion-protein-derived peptides with potent antiviral activity in vivo. PLoS One. 2012;7(5):e36833. doi: 10.1371/journal.pone.0036833. Epub 2012 May 16. PMID: 22666328

10. Porotto M, Salah Z, DeVito I, Talekar A, Palmer SG, R., Wilson IA, Moscona A. The second receptor binding site of the globular head of the Newcastle disease virus (NDV) hemagglutinin-neuraminidase activates the stalk of multiple paramyxoviruses to trigger fusion. J Virol. 2012 May;86(10):5730-41. doi: 10.1128/JVI.06793-11. Epub 2012 Mar 21. PMID: 22438532

11. Talekar A, SenGupta U, Moscona A, Glickman F, Briese T, Whitt M, Pessi P, Mathieu C, Horvat B, Porotto M. Rapid Development of Treatments and Screening systems for Emerging Viral Diseases. PLoS One. 2012;7(3):e30538. doi: 10.1371/journal.pone.0030538. Epub 2012 Mar 2. PMID: 22396728

12. Porotto M, Palmer SG, Palermo LM, 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. doi: 10.1074/jbc.M111.298059. Epub 2011 Nov 22. PMID: 22110138

13. Lee KK, Pessi P, Gui L, Santoprete A, Talekar A, Moscona A, Porotto M. (2011) Capturing a fusion intermediate of influenza hemagglutinin with a cholesterol-conjugated peptide: a new antiviral strategy for influenza virus. J Biol Chem. 286: 42141-42149. doi: 10.1074/jbc.M111.254243. Epub 2011 Oct 12. PMID: 21994935

14. Porotto M, DeVito I, Palmer SG, Jurgens EM, Yee JL, Yokoyama CC, Pessi A, 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. doi: 10.1128/JVI.05873-11. Epub 2011 Oct 5. PMID: 21976650

15. Talekar A, Pessi P, Porotto M. (2011) Infection of primary neurons mediated by nipah virus envelope proteins: role of host target cells in antiviral action. J Virol. 85: 8422-8426. doi: 10.1128/JVI.00452-11. Epub 2011 Jun 8. PMID: 21653662

16. Porotto M, Yi F, Moscona A, LaVan DA. (2011) Synthetic protocells interact with viral nanomachinery and inactivate pathogenic human virus. PLoS One. 6: e16874. doi: 10.1371/journal.pone.0016874. PMID: 21390296

17. Porotto M, Rockx B, Yokoyama CC, Talekar A, DeVito I, Palermo LM, Cortese R, Lu M, Feldmann H, Pessi A, Moscona A. (2010) Inhibition of Nipah virus infection in vivo: Targeting an early stage of paramyxovirus fusion activation during viral entry. PLoS Pathog. 6: e1001168. doi:10.1371/journal.ppat.1001168. PMID: 21060819

18. Porotto M*, Yokoyama C, Palermo LM, Mungall B, Aljofan M, Cortese R, Pessi A, Moscona A.* (2010) Viral entry inhibitors targeted to the membrane site of action. J Virol. 84: 6760-7608. doi: 10.1128/JVI.00135-10. Epub 2010 Mar 31. PMID: 20357085 *Co-corresponding

Department of Pediatrics, Columbia University 630 West 168th Street CHC 1-102 Central New York, NY 10032 Tel. 212-305-5831