Header Logo

Ronald M Iorio PhD

InstitutionUMass Chan Medical School
DepartmentMicrobiology and Physiological Systems
AddressUMass Chan Medical School
55 Lake Avenue North
Worcester MA 01655
vCardDownload vCard
    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentMicrobiology and Physiological Systems

    InstitutionMorningside Graduate School of Biomedical Sciences
    DepartmentImmunology and Microbiology Program

    Collapse Biography 
    Collapse education and training
    University of Massachusetts Boston, Boston, MA, United StatesBABiology
    Boston College, Chestnut Hill, MA, United StatesMSBiology
    Boston College, Chestnut Hill, MA, United StatesPHDBiology

    Collapse Overview 
    Collapse overview

    Academic Background

    BA, University of Massachusetts
    MS, PhD, Boston College

    Viral pathogenesis and virulence; viral entry and the mechanism of virus-induced membrane fusion; viral glycoproteins and receptors

    Paramyxoviruses are enveloped, negative-stranded RNA viruses, which include clinically important human pathogens such as measles, mumps, parainfluenza, and respiratory syncytial viruses; important animal pathogens, such as Newcastle disease (NDV), and Sendai viruses; and, emerging viruses such as Nipah and Hendra. Though primarily respiratory pathogens, several members of the group are capable of causing central nervous system disease. We are interested in understanding the molecular basis for the pathogenesis and virulence of this group of viruses.

    Paramyxoviruses gain entry into the cell by mediating direct fusion of the virus and cell membranes. Fusion involves a virus-specific interaction between the two viral surface glycoprotein spikes, the attachment protein and the fusion protein. Mediated through this interaction, receptor binding by the attachment protein is thought to trigger a conformational change in the fusion protein from a metastable, pre-fusion form to a fusion-active form. We are exploring various aspects of the fusion process for several paramyxoviruses. We have developed a sensitive co-immunoprecipitation assay to detect the attachment-fusion protein complex at the cell surface and have identified mutations in several paramyxovirus attachment proteins that block fusion by modulating the interaction between the two surface glycoproteins. Our evidence is consistent with the idea that the attachment protein - fusion protein interaction regulates fusion by a different mechanism in viruses such as NDV, which recognize the ubiquitous sugar sialic acid as receptor, and viruses such as measles, which recognize specific proteins as receptors.

    NDV virulence involves contributions from at least three viral proteins. The site of cleavage activation of the fusion protein is a major determinant of virulence. However, recent evidence has revealed that the attachment protein also plays a role. In addition, the V protein, produced by RNA editing from the P gene, is an interferon antagonist and thereby also plays a role in virulence. We are interested in understanding the mechanisms by which all three proteins exert their effects on NDV virulence, as well as the basis for the differences in virulence observed among members of the NDV serotype.

    Collapse Rotation Projects

    Rotation Projects

    Rotation projects will involve construction of site-directed mutants or chimeras of either the attachment, fusion or V proteins and evaluation of their ability to promote the functions attributed to that protein. Depending on the target protein, the structure and function of each mutated or chimeric protein will be evaluated using several functional assays. These include flow cytometry (cell surface expression and antibody recognition), hemadsorption of red blood cells (receptor recognition activity), neuraminidase (receptor destroying activity), content mixing reporter gene assay (fusion), immunoprecipitation and SDS-PAGE (protein structure) and co-immunoprecipitation (determination of the ability of the mutated proteins to interact with a co-expressed protein). For the V protein, we will be evaluating various aspects of its interferon inhibitory activity.

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Ortega V, Stone JA, Contreras EM, Iorio RM, Aguilar HC. Addicted to sugar: roles of glycans in the order Mononegavirales. Glycobiology. 2019 01 01; 29(1):2-21. PMID: 29878112.
      Citations: 10     Fields:    Translation:HumansAnimalsCells
    2. Wei Y, Zhang Y, Cai H, Mirza AM, Iorio RM, Peeples ME, Niewiesk S, Li J. Roles of the putative integrin-binding motif of the human metapneumovirus fusion (f) protein in cell-cell fusion, viral infectivity, and pathogenesis. J Virol. 2014 Apr; 88(8):4338-52. PMID: 24478423.
      Citations: 25     Fields:    Translation:HumansAnimalsCells
    3. Liu Q, Stone JA, Bradel-Tretheway B, Dabundo J, Benavides Montano JA, Santos-Montanez J, Biering SB, Nicola AV, Iorio RM, Lu X, Aguilar HC. Unraveling a three-step spatiotemporal mechanism of triggering of receptor-induced Nipah virus fusion and cell entry. PLoS Pathog. 2013; 9(11):e1003770. PMID: 24278018.
      Citations: 67     Fields:    Translation:AnimalsCells
    4. Mirza AM, Iorio RM. A mutation in the stalk of the newcastle disease virus hemagglutinin-neuraminidase (HN) protein prevents triggering of the F protein despite allowing efficient HN-F complex formation. J Virol. 2013 Aug; 87(15):8813-5. PMID: 23740987.
      Citations: 14     Fields:    Translation:Cells
    5. Zhu Q, Biering SB, Mirza AM, Grasseschi BA, Mahon PJ, Lee B, Aguilar HC, Iorio RM. Individual N-glycans added at intervals along the stalk of the Nipah virus G protein prevent fusion but do not block the interaction with the homologous F protein. J Virol. 2013 Mar; 87(6):3119-29. PMID: 23283956.
      Citations: 14     Fields:    Translation:Cells
    6. Wei Y, Feng K, Yao X, Cai H, Li J, Mirza AM, Iorio RM, Li J. Localization of a region in the fusion protein of avian metapneumovirus that modulates cell-cell fusion. J Virol. 2012 Nov; 86(21):11800-14. PMID: 22915815.
      Citations: 9     Fields:    Translation:AnimalsCells
    7. Aguilar HC, Iorio RM. Henipavirus membrane fusion and viral entry. Curr Top Microbiol Immunol. 2012; 359:79-94. PMID: 22427111.
      Citations: 38     Fields:    Translation:HumansAnimalsCells
    8. Mahon PJ, Mirza AM, Iorio RM. Role of the two sialic acid binding sites on the newcastle disease virus HN protein in triggering the interaction with the F protein required for the promotion of fusion. J Virol. 2011 Nov; 85(22):12079-82. PMID: 21880745.
      Citations: 31     Fields:    Translation:Cells
    9. Plemper RK, Brindley MA, Iorio RM. Structural and mechanistic studies of measles virus illuminate paramyxovirus entry. PLoS Pathog. 2011 Jun; 7(6):e1002058. PMID: 21655106.
      Citations: 59     Fields:    Translation:HumansCells
    10. Mirza AM, Aguilar HC, Zhu Q, Mahon PJ, Rota PA, Lee B, Iorio RM. Triggering of the newcastle disease virus fusion protein by a chimeric attachment protein that binds to Nipah virus receptors. J Biol Chem. 2011 May 20; 286(20):17851-60. PMID: 21460213.
      Citations: 25     Fields:    Translation:AnimalsCells
    11. Alamares JG, Elankumaran S, Samal SK, Iorio RM. The interferon antagonistic activities of the V proteins from two strains of Newcastle disease virus correlate with their known virulence properties. Virus Res. 2010 Jan; 147(1):153-7. PMID: 19896994.
      Citations: 24     Fields:    Translation:AnimalsCells
    12. Iorio RM, Melanson VR, Mahon PJ. Glycoprotein interactions in paramyxovirus fusion. Future Virol. 2009 Jul 01; 4(4):335-351. PMID: 20161127.
    13. Corey EA, Iorio RM. Measles virus attachment proteins with impaired ability to bind CD46 interact more efficiently with the homologous fusion protein. Virology. 2009 Jan 05; 383(1):1-5. PMID: 19013625.
      Citations: 15     Fields:    Translation:Cells
    14. Mahon PJ, Mirza AM, Musich TA, Iorio RM. Engineered intermonomeric disulfide bonds in the globular domain of Newcastle disease virus hemagglutinin-neuraminidase protein: implications for the mechanism of fusion promotion. J Virol. 2008 Nov; 82(21):10386-96. PMID: 18753211.
      Citations: 28     Fields:    Translation:AnimalsCells
    15. Iorio RM, Mahon PJ. Paramyxoviruses: different receptors - different mechanisms of fusion. Trends Microbiol. 2008 Apr; 16(4):135-7. PMID: 18346895.
      Citations: 39     Fields:    Translation:HumansAnimalsCells
    16. Corey EA, Iorio RM. Mutations in the stalk of the measles virus hemagglutinin protein decrease fusion but do not interfere with virus-specific interaction with the homologous fusion protein. J Virol. 2007 Sep; 81(18):9900-10. PMID: 17626104.
      Citations: 59     Fields:    Translation:HumansCells
    17. Melanson VR, Iorio RM. Addition of N-glycans in the stalk of the Newcastle disease virus HN protein blocks its interaction with the F protein and prevents fusion. J Virol. 2006 Jan; 80(2):623-33. PMID: 16378965.
      Citations: 66     Fields:    Translation:AnimalsCells
    18. Alamares JG, Li J, Iorio RM. Monoclonal antibody routinely used to identify avirulent strains of Newcastle disease virus binds to an epitope at the carboxy terminus of the hemagglutinin-neuraminidase protein and recognizes individual mesogenic and velogenic strains. J Clin Microbiol. 2005 Aug; 43(8):4229-33. PMID: 16081986.
      Citations: 2     Fields:    Translation:Cells
    19. Li J, Melanson VR, Mirza AM, Iorio RM. Decreased dependence on receptor recognition for the fusion promotion activity of L289A-mutated newcastle disease virus fusion protein correlates with a monoclonal antibody-detected conformational change. J Virol. 2005 Jan; 79(2):1180-90. PMID: 15613345.
      Citations: 14     Fields:    Translation:AnimalsCells
    20. Melanson VR, Iorio RM. Amino acid substitutions in the F-specific domain in the stalk of the newcastle disease virus HN protein modulate fusion and interfere with its interaction with the F protein. J Virol. 2004 Dec; 78(23):13053-61. PMID: 15542657.
      Citations: 73     Fields:    Translation:AnimalsCells
    21. Li J, Quinlan E, Mirza A, Iorio RM. Mutated form of the Newcastle disease virus hemagglutinin-neuraminidase interacts with the homologous fusion protein despite deficiencies in both receptor recognition and fusion promotion. J Virol. 2004 May; 78(10):5299-310. PMID: 15113911.
      Citations: 38     Fields:    Translation:AnimalsCells
    22. Wang Z, Mirza AM, Li J, Mahon PJ, Iorio RM. An oligosaccharide at the C-terminus of the F-specific domain in the stalk of the human parainfluenza virus 3 hemagglutinin-neuraminidase modulates fusion. Virus Res. 2004 Feb; 99(2):177-85. PMID: 14749183.
      Citations: 24     Fields:    Translation:AnimalsCells
    23. Corey EA, Mirza AM, Levandowsky E, Iorio RM. Fusion deficiency induced by mutations at the dimer interface in the Newcastle disease virus hemagglutinin-neuraminidase is due to a temperature-dependent defect in receptor binding. J Virol. 2003 Jun; 77(12):6913-22. PMID: 12768010.
      Citations: 40     Fields:    Translation:AnimalsCells
    24. Iorio RM, Field GM, Sauvron JM, Mirza AM, Deng R, Mahon PJ, Langedijk JP. Structural and functional relationship between the receptor recognition and neuraminidase activities of the Newcastle disease virus hemagglutinin-neuraminidase protein: receptor recognition is dependent on neuraminidase activity. J Virol. 2001 Feb; 75(4):1918-27. PMID: 11160691.
      Citations: 51     Fields:    Translation:AnimalsCells
    25. Deng R, Wang Z, Mahon PJ, Marinello M, Mirza A, Iorio RM. Mutations in the Newcastle disease virus hemagglutinin-neuraminidase protein that interfere with its ability to interact with the homologous F protein in the promotion of fusion. Virology. 1999 Jan 05; 253(1):43-54. PMID: 9887317.
      Citations: 55     Fields:    Translation:AnimalsCells
    26. Deng R, Mirza AM, Mahon PJ, Iorio RM. Functional chimeric HN glycoproteins derived from Newcastle disease virus and human parainfluenza virus-3. Arch Virol Suppl. 1997; 13:115-30. PMID: 9413532.
      Citations: 29     Fields:    Translation:HumansAnimalsCells
    27. Deng R, Wang Z, Mirza AM, Iorio RM. Localization of a domain on the paramyxovirus attachment protein required for the promotion of cellular fusion by its homologous fusion protein spike. Virology. 1995 Jun 01; 209(2):457-69. PMID: 7778280.
      Citations: 92     Fields:    Translation:AnimalsCells
    28. Deng R, Wang Z, Glickman RL, Iorio RM. Glycosylation within an antigenic site on the HN glycoprotein of Newcastle disease virus interferes with its role in the promotion of membrane fusion. Virology. 1994 Oct; 204(1):17-26. PMID: 7522370.
      Citations: 11     Fields:    Translation:Cells
    29. Mirza AM, Deng R, Iorio RM. Site-directed mutagenesis of a conserved hexapeptide in the paramyxovirus hemagglutinin-neuraminidase glycoprotein: effects on antigenic structure and function. J Virol. 1994 Aug; 68(8):5093-9. PMID: 8035509.
      Citations: 41     Fields:    Translation:Cells
    30. Mirza AM, Sheehan JP, Hardy LW, Glickman RL, Iorio RM. Structure and function of a membrane anchor-less form of the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus. J Biol Chem. 1993 Oct 05; 268(28):21425-31. PMID: 8407985.
      Citations: 24     Fields:    Translation:AnimalsCells
    31. Iorio RM, Glickman RL. Fusion mutants of Newcastle disease virus selected with monoclonal antibodies to the hemagglutinin-neuraminidase. J Virol. 1992 Nov; 66(11):6626-33. PMID: 1404607.
      Citations: 11     Fields:    Translation:Cells
    32. Sheehan JP, Iorio RM. A single amino acid substitution in the hemagglutinin-neuraminidase of Newcastle disease virus results in a protein deficient in both functions. Virology. 1992 Aug; 189(2):778-81. PMID: 1641990.
      Citations: 13     Fields:    Translation:AnimalsCells
    33. Iorio RM, Glickman RL, Sheehan JP. Inhibition of fusion by neutralizing monoclonal antibodies to the haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus. J Gen Virol. 1992 May; 73 ( Pt 5):1167-76. PMID: 1375279.
      Citations: 23     Fields:    Translation:AnimalsCells
    34. Iorio RM, Syddall RJ, Sheehan JP, Bratt MA, Glickman RL, Riel AM. Neutralization map of the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus: domains recognized by monoclonal antibodies that prevent receptor recognition. J Virol. 1991 Sep; 65(9):4999-5006. PMID: 1651419.
      Citations: 54     Fields:    Translation:AnimalsCells
    35. Iorio RM, Syddall RJ, Glickman RL, Riel AM, Sheehan JP, Bratt MA. Identification of amino acid residues important to the neuraminidase activity of the HN glycoprotein of Newcastle disease virus. Virology. 1989 Nov; 173(1):196-204. PMID: 2479168.
      Citations: 18     Fields:    Translation:AnimalsCells
    36. Iorio RM, Glickman RL, Riel AM, Sheehan JP, Bratt MA. Functional and neutralization profile of seven overlapping antigenic sites on the HN glycoprotein of Newcastle disease virus: monoclonal antibodies to some sites prevent viral attachment. Virus Res. 1989 Jul; 13(3):245-61. PMID: 2475989.
      Citations: 40     Fields:    Translation:AnimalsCells
    37. Iorio RM. Mechanisms of neutralization of animal viruses: monoclonal antibodies provide a new perspective. Microb Pathog. 1988 Jul; 5(1):1-7. PMID: 2854186.
      Citations: 2     Fields:    Translation:Cells
    38. Glickman RL, Syddall RJ, Iorio RM, Sheehan JP, Bratt MA. Quantitative basic residue requirements in the cleavage-activation site of the fusion glycoprotein as a determinant of virulence for Newcastle disease virus. J Virol. 1988 Jan; 62(1):354-6. PMID: 3275436.
      Citations: 85     Fields:    Translation:Cells
    39. Sheehan JP, Iorio RM, Syddall RJ, Glickman RL, Bratt MA. Reducing agent-sensitive dimerization of the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus correlates with the presence of cysteine at residue 123. Virology. 1987 Dec; 161(2):603-6. PMID: 3686832.
      Citations: 20     Fields:    Translation:Cells
    Iorio's Networks
    Click the
    buttons for more information and interactive visualizations!
    Concepts (136)
    Similar People (60)
    Same Department Expand Description
    Physical Neighbors