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Luis Martinez-Sobrido

TitleAssociate Professor
InstitutionSchool of Medicine and Dentistry
DepartmentMicrobiology and Immunology
AddressUniversity of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 672
Rochester NY 14642
 
 Awards And Honors
1996 - 2000- Graduate Fellowship: Evaluation of interactions among human respiratory syncytial virus (HRSV) ribonucleoprotein components.  | Ministerio de Sanidad (National Institute of Health)
2005     - International Society for Interferon and Cytokine Research Travel Award for the 2005 ISICR meeting in Shangai, China.  | ISICR
2006     - International Society for Interferon and Cytokine Research Travel Award for the 2006 ISICR meeting in Vienna, Austria  | ISICR
2007     - International Society for Interferon and Cytokine Research Young Investigator Award for the 2007 ISICR meeting in Oxford  | ISICR
2008     - American Society for Virology travel award to attend the XVIth International Congress of Virology in Istanbul, Turkey.  | American Society for Virology
2010     - Special Recognition from the NIAID, Division of Microbiology and Infectious Disease for H1N1 influenza work  | NIAID
2011     - ASM International Professorship for Latin America and the Caribbean  | American Society for Microbiology
 
 Overview
My research interest for the last decade has been focused on the molecular biology, immunology, and pathogenesis of negative-strand (Influenza viruses, Respiratory Syncytial Virus, Human Metapneumovirus, arenavirus, Thogoto virus, Ebola virus, Crimean Congo Hemorrhagic Fever virus) and positive-strand (Dengue virus, SARS coronavirus, Mouse Hepatitis virus) RNA, and DNA viruses. I have extensive knowledge in reverse genetics techniques for rescuing RNA and DNA viruses, pioneered the development of techniques and screening assays to identify viral-encoded interferon antagonist proteins, and established new molecular biology techniques to study highly pathogenic viruses without the requirement of special biosafety conditions. My major contributions to the virology field include the development of new experimental systems to answer difficult questions in the mechanisms of virus-host interactions, including: 1) Reverse genetics tools to genetically manipulate viruses, that I have used to examine virus-host interactions and development of vaccines; 2) Plasmid, virus and cellular based assays for the identification of virus-encoded IFN-antagonist proteins that I have used to uncover molecular mechanisms involved in viral pathogenesis, including the first description of an IFN antagonist protein in the arenavirus family and the multiple anti-IFN actions of influenza virus NS1; and 3) Single-cycle infectious influenza and arenaviruses to study highly pathogenic viruses, without the requirement of special biosafety conditions.
Since my recent appointment in the Department of Microbiology and Immunology at University of Rochester, one of the 5 NIAID Centers of Excellence for Influenza Research and Surveillance, my research has focused on the interactions of influenza and arenavirus proteins with the host cell. My experience in molecular biology, virus reverse genetics techniques, and virus-based bioassays to study the interferon response gives me the unique opportunity to carry out innovative and original research projects, the major objective of which is to shed light and understand the molecular determinants of patogenesis of influenza and arenaviruses and how these viruses interact with their hosts.

 
 Selected Publications
List All   |   Timeline
  1. Domm W, Brewer M, Baker SF, Feng C, Martínez-Sobrido L, Treanor J, Dewhurst S. Use of bacteriophage particles displaying influenza virus hemagglutinin for the detection of hemagglutination-inhibition antibodies. J Virol Methods. 2014 Mar; 197:47-50.
    View in: PubMed
  2. Ortiz-Riaño E, Ngo N, Devito S, Eggink D, Munger J, Shaw ML, de la Torre JC, Martínez-Sobrido L. Inhibition of arenavirus by a3, a pyrimidine biosynthesis inhibitor. J Virol. 2014 Jan; 88(2):878-89.
    View in: PubMed
  3. Ayllon J, García-Sastre A, Martínez-Sobrido L. Rescue of recombinant Newcastle disease virus from cDNA. J Vis Exp. 2013; (80).
    View in: PubMed
  4. Bauman JD, Patel D, Baker SF, Vijayan RS, Xiang A, Parhi AK, Martínez-Sobrido L, Lavoie EJ, Das K, Arnold E. Crystallographic fragment screening and structure-based optimization yields a new class of influenza endonuclease inhibitors. ACS Chem Biol. 2013 Nov 15; 8(11):2501-8.
    View in: PubMed
  5. Cheng BY, Ortiz-Riaño E, de la Torre JC, Martínez-Sobrido L. Generation of recombinant arenavirus for vaccine development in FDA-approved Vero cells. J Vis Exp. 2013; (78).
    View in: PubMed
  6. Baker SF, Guo H, Albrecht RA, García-Sastre A, Topham DJ, Martínez-Sobrido L. Protection against Lethal Influenza with a Viral Mimic. J Virol. 2013 Aug; 87(15):8591-605.
    View in: PubMed
  7. Ortiz-Riaño E, Cheng BY, Carlos de la Torre J, Martínez-Sobrido L. Arenavirus reverse genetics for vaccine development. J Gen Virol. 2013 Jun; 94(Pt 6):1175-88.
    View in: PubMed
  8. Ortiz-Riaño E, Cheng BY, de la Torre JC, Martínez-Sobrido L. D471G mutation in LCMV-NP affects its ability to self-associate and results in a dominant negative effect in viral RNA synthesis. Viruses. 2012 Oct; 4(10):2137-61.
    View in: PubMed
  9. Rodrigo WW, Ortiz-Riaño E, Pythoud C, Kunz S, de la Torre JC, Martínez-Sobrido L. Arenavirus nucleoproteins prevent activation of nuclear factor kappa B. J Virol. 2012 Aug; 86(15):8185-97.
    View in: PubMed
  10. Pythoud C, Rodrigo WW, Pasqual G, Rothenberger S, Martínez-Sobrido L, de la Torre JC, Kunz S. Arenavirus nucleoprotein targets interferon regulatory factor-activating kinase IKKe. J Virol. 2012 Aug; 86(15):7728-38.
    View in: PubMed
  11. Ortiz-Riaño E, Cheng BY, de la Torre JC, Martínez-Sobrido L. Self-association of lymphocytic choriomeningitis virus nucleoprotein is mediated by its N-terminal region and is not required for its anti-interferon function. J Virol. 2012 Mar; 86(6):3307-17.
    View in: PubMed
  12. Guerra S, Abaitua F, Martínez-Sobrido L, Esteban M, García-Sastre A, Rodríguez D. Host-range restriction of vaccinia virus E3L deletion mutant can be overcome in vitro, but not in vivo, by expression of the influenza virus NS1 protein. PLoS One. 2011; 6(12):e28677.
    View in: PubMed
  13. Ortiz-Riaño E, Cheng BY, de la Torre JC, Martínez-Sobrido L. The C-terminal region of lymphocytic choriomeningitis virus nucleoprotein contains distinct and segregable functional domains involved in NP-Z interaction and counteraction of the type I interferon response. J Virol. 2011 Dec; 85(24):13038-48.
    View in: PubMed
  14. Bortz E, Westera L, Maamary J, Steel J, Albrecht RA, Manicassamy B, Chase G, Martínez-Sobrido L, Schwemmle M, García-Sastre A. Host- and strain-specific regulation of influenza virus polymerase activity by interacting cellular proteins. MBio. 2011; 2(4).
    View in: PubMed
  15. Davtyan H, Ghochikyan A, Cadagan R, Zamarin D, Petrushina I, Movsesyan N, Martinez-Sobrido L, Albrecht RA, García-Sastre A, Agadjanyan MG. The immunological potency and therapeutic potential of a prototype dual vaccine against influenza and Alzheimer's disease. J Transl Med. 2011; 9:127.
    View in: PubMed
  16. Moreno JL, Kurita M, Holloway T, López J, Cadagan R, Martínez-Sobrido L, García-Sastre A, González-Maeso J. Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT2A and mGlu2 receptors in the adult offspring. J Neurosci. 2011 Feb 2; 31(5):1863-72.
    View in: PubMed
  17. Kou Z, Lim JY, Beltramello M, Quinn M, Chen H, Liu S, Liu SN, Martinez-Sobrido L, Martnez-Sobrido L, Diamond MS, Schlesinger JJ, de Silva A, Sallusto F, Jin X. Human antibodies against dengue enhance dengue viral infectivity without suppressing type I interferon secretion in primary human monocytes. Virology. 2011 Feb 5; 410(1):240-7.
    View in: PubMed
  18. Rodrigo WW, de la Torre JC, Martínez-Sobrido L. Use of single-cycle infectious lymphocytic choriomeningitis virus to study hemorrhagic fever arenaviruses. J Virol. 2011 Feb; 85(4):1684-95.
    View in: PubMed
  19. Wortman MJ, Hanson LK, Martínez-Sobrido L, Campbell AE, Nance JA, García-Sastre A, Johnson EM. Regulation of PURA gene transcription by three promoters generating distinctly spliced 5-prime leaders: a novel means of fine control over tissue specificity and viral signals. BMC Mol Biol. 2010; 11:81.
    View in: PubMed
  20. Borrow P, Martínez-Sobrido L, de la Torre JC. Inhibition of the type I interferon antiviral response during arenavirus infection. Viruses. 2010 Nov; 2(11):2443-80.
    View in: PubMed
  21. Kim D, Martinez-Sobrido L, Choi C, Petroff N, García-Sastre A, Niewiesk S, Carsillo T. Induction of type I interferon secretion through recombinant Newcastle disease virus expressing measles virus hemagglutinin stimulates antibody secretion in the presence of maternal antibodies. J Virol. 2011 Jan; 85(1):200-7.
    View in: PubMed
  22. Steidle S, Martínez-Sobrido L, Mordstein M, Lienenklaus S, García-Sastre A, Stäheli P, Kochs G. Glycine 184 in nonstructural protein NS1 determines the virulence of influenza A virus strain PR8 without affecting the host interferon response. J Virol. 2010 Dec; 84(24):12761-70.
    View in: PubMed
  23. Martínez-Sobrido L, García-Sastre A. Generation of recombinant influenza virus from plasmid DNA. J Vis Exp. 2010; (42).
    View in: PubMed
  24. Rose KM, Elliott R, Martínez-Sobrido L, García-Sastre A, Weiss SR. Murine coronavirus delays expression of a subset of interferon-stimulated genes. J Virol. 2010 Jun; 84(11):5656-69.
    View in: PubMed
  25. Martínez-Sobrido L, Cadagan R, Steel J, Basler CF, Palese P, Moran TM, García-Sastre A. Hemagglutinin-pseudotyped green fluorescent protein-expressing influenza viruses for the detection of influenza virus neutralizing antibodies. J Virol. 2010 Feb; 84(4):2157-63.
    View in: PubMed
  26. Buettner N, Vogt C, Martínez-Sobrido L, Weber F, Waibler Z, Kochs G. Thogoto virus ML protein is a potent inhibitor of the interferon regulatory factor-7 transcription factor. J Gen Virol. 2010 Jan; 91(Pt 1):220-7.
    View in: PubMed
  27. Kochs G, Martínez-Sobrido L, Lienenklaus S, Weiss S, García-Sastre A, Staeheli P. Strong interferon-inducing capacity of a highly virulent variant of influenza A virus strain PR8 with deletions in the NS1 gene. J Gen Virol. 2009 Dec; 90(Pt 12):2990-4.
    View in: PubMed
  28. Martínez-Sobrido L, Emonet S, Giannakas P, Cubitt B, García-Sastre A, de la Torre JC. Identification of amino acid residues critical for the anti-interferon activity of the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus. J Virol. 2009 Nov; 83(21):11330-40.
    View in: PubMed
  29. Kuri T, Zhang X, Habjan M, Martínez-Sobrido L, García-Sastre A, Yuan Z, Weber F. Interferon priming enables cells to partially overturn the SARS coronavirus-induced block in innate immune activation. J Gen Virol. 2009 Nov; 90(Pt 11):2686-94.
    View in: PubMed
  30. Nguyen DN, Kim P, Martínez-Sobrido L, Beitzel B, García-Sastre A, Langer R, Anderson DG. A novel high-throughput cell-based method for integrated quantification of type I interferons and in vitro screening of immunostimulatory RNA drug delivery. Biotechnol Bioeng. 2009 Jul 1; 103(4):664-75.
    View in: PubMed
  31. Dauber B, Martínez-Sobrido L, Schneider J, Hai R, Waibler Z, Kalinke U, García-Sastre A, Wolff T. Influenza B virus ribonucleoprotein is a potent activator of the antiviral kinase PKR. PLoS Pathog. 2009 Jun; 5(6):e1000473.
    View in: PubMed
  32. Zamarin D, Martínez-Sobrido L, Kelly K, Mansour M, Sheng G, Vigil A, García-Sastre A, Palese P, Fong Y. Enhancement of oncolytic properties of recombinant newcastle disease virus through antagonism of cellular innate immune responses. Mol Ther. 2009 Apr; 17(4):697-706.
    View in: PubMed
  33. Lai C, Struckhoff JJ, Schneider J, Martinez-Sobrido L, Wolff T, García-Sastre A, Zhang DE, Lenschow DJ. Mice lacking the ISG15 E1 enzyme UbE1L demonstrate increased susceptibility to both mouse-adapted and non-mouse-adapted influenza B virus infection. J Virol. 2009 Jan; 83(2):1147-51.
    View in: PubMed
  34. Hai R, Martínez-Sobrido L, Fraser KA, Ayllon J, García-Sastre A, Palese P. Influenza B virus NS1-truncated mutants: live-attenuated vaccine approach. J Virol. 2008 Nov; 82(21):10580-90.
    View in: PubMed
  35. Andersson I, Karlberg H, Mousavi-Jazi M, Martínez-Sobrido L, Weber F, Mirazimi A. Crimean-Congo hemorrhagic fever virus delays activation of the innate immune response. J Med Virol. 2008 Aug; 80(8):1397-404.
    View in: PubMed
  36. Muñoz-Fontela C, Macip S, Martínez-Sobrido L, Brown L, Ashour J, García-Sastre A, Lee SW, Aaronson SA. Transcriptional role of p53 in interferon-mediated antiviral immunity. J Exp Med. 2008 Aug 4; 205(8):1929-38.
    View in: PubMed
  37. Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, Akira S, Gill MA, García-Sastre A, Katze MG, Gale M. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol. 2008 Jan; 82(1):335-45.
    View in: PubMed
  38. Martínez-Sobrido L, Giannakas P, Cubitt B, García-Sastre A, de la Torre JC. Differential inhibition of type I interferon induction by arenavirus nucleoproteins. J Virol. 2007 Nov; 81(22):12696-703.
    View in: PubMed
  39. Vigil A, Park MS, Martinez O, Chua MA, Xiao S, Cros JF, Martínez-Sobrido L, Woo SL, García-Sastre A. Use of reverse genetics to enhance the oncolytic properties of Newcastle disease virus. Cancer Res. 2007 Sep 1; 67(17):8285-92.
    View in: PubMed
  40. Roth-Cross JK, Martínez-Sobrido L, Scott EP, García-Sastre A, Weiss SR. Inhibition of the alpha/beta interferon response by mouse hepatitis virus at multiple levels. J Virol. 2007 Jul; 81(13):7189-99.
    View in: PubMed
  41. He Q, Martinez-Sobrido L, Eko FO, Palese P, Garcia-Sastre A, Lyn D, Okenu D, Bandea C, Ananaba GA, Black CM, Igietseme JU. Live-attenuated influenza viruses as delivery vectors for Chlamydia vaccines. Immunology. 2007 Sep; 122(1):28-37.
    View in: PubMed
  42. Kochs G, García-Sastre A, Martínez-Sobrido L. Multiple anti-interferon actions of the influenza A virus NS1 protein. J Virol. 2007 Jul; 81(13):7011-21.
    View in: PubMed
  43. Grimm D, Staeheli P, Hufbauer M, Koerner I, Martínez-Sobrido L, Solórzano A, García-Sastre A, Haller O, Kochs G. Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene. Proc Natl Acad Sci U S A. 2007 Apr 17; 104(16):6806-11.
    View in: PubMed
  44. Mayer D, Molawi K, Martínez-Sobrido L, Ghanem A, Thomas S, Baginsky S, Grossmann J, García-Sastre A, Schwemmle M. Identification of cellular interaction partners of the influenza virus ribonucleoprotein complex and polymerase complex using proteomic-based approaches. J Proteome Res. 2007 Feb; 6(2):672-82.
    View in: PubMed
  45. Stertz S, Reichelt M, Spiegel M, Kuri T, Martínez-Sobrido L, García-Sastre A, Weber F, Kochs G. The intracellular sites of early replication and budding of SARS-coronavirus. Virology. 2007 May 10; 361(2):304-15.
    View in: PubMed
  46. Kopecky-Bromberg SA, Martínez-Sobrido L, Frieman M, Baric RA, Palese P. Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J Virol. 2007 Jan; 81(2):548-57.
    View in: PubMed
  47. Mibayashi M, Martínez-Sobrido L, Loo YM, Cárdenas WB, Gale M, García-Sastre A. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J Virol. 2007 Jan; 81(2):514-24.
    View in: PubMed
  48. Martínez-Sobrido L, Zúñiga EI, Rosario D, García-Sastre A, de la Torre JC. Inhibition of the type I interferon response by the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus. J Virol. 2006 Sep; 80(18):9192-9.
    View in: PubMed
  49. Cárdenas WB, Loo YM, Gale M, Hartman AL, Kimberlin CR, Martínez-Sobrido L, Saphire EO, Basler CF. Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J Virol. 2006 Jun; 80(11):5168-78.
    View in: PubMed
  50. Martinez-Sobrido L, Gitiban N, Fernandez-Sesma A, Cros J, Mertz SE, Jewell NA, Hammond S, Flano E, Durbin RK, García-Sastre A, Durbin JE. Protection against respiratory syncytial virus by a recombinant Newcastle disease virus vector. J Virol. 2006 Feb; 80(3):1130-9.
    View in: PubMed
  51. Kopecky-Bromberg SA, Martinez-Sobrido L, Palese P. 7a protein of severe acute respiratory syndrome coronavirus inhibits cellular protein synthesis and activates p38 mitogen-activated protein kinase. J Virol. 2006 Jan; 80(2):785-93.
    View in: PubMed
  52. Muñoz-Jordán JL, Laurent-Rolle M, Ashour J, Martínez-Sobrido L, Ashok M, Lipkin WI, García-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul; 79(13):8004-13.
    View in: PubMed
  53. García-Barreno B, Steel J, Payá M, Martínez-Sobrido L, Delgado T, Yeo RP, Melero JA. Epitope mapping of human respiratory syncytial virus 22K transcription antitermination factor: role of N-terminal sequences in protein folding. J Gen Virol. 2005 Apr; 86(Pt 4):1103-7.
    View in: PubMed
  54. Spiegel M, Pichlmair A, Martínez-Sobrido L, Cros J, García-Sastre A, Haller O, Weber F. Inhibition of Beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two-step model for activation of interferon regulatory factor 3. J Virol. 2005 Feb; 79(4):2079-86.
    View in: PubMed
  55. Jennings S, Martínez-Sobrido L, García-Sastre A, Weber F, Kochs G. Thogoto virus ML protein suppresses IRF3 function. Virology. 2005 Jan 5; 331(1):63-72.
    View in: PubMed
  56. Vecino WH, Quanquin NM, Martinez-Sobrido L, Fernandez-Sesma A, García-Sastre A, Jacobs WR, Fennelly GJ. Mucosal immunization with attenuated Shigella flexneri harboring an influenza hemagglutinin DNA vaccine protects mice against a lethal influenza challenge. Virology. 2004 Aug 1; 325(2):192-9.
    View in: PubMed
  57. Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Mühlberger E, Bray M, Klenk HD, Palese P, García-Sastre A. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol. 2003 Jul; 77(14):7945-56.
    View in: PubMed
  58. Schickli JH, Flandorfer A, Nakaya T, Martinez-Sobrido L, García-Sastre A, Palese P. Plasmid-only rescue of influenza A virus vaccine candidates. Philos Trans R Soc Lond B Biol Sci. 2001 Dec 29; 356(1416):1965-73.
    View in: PubMed

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