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Elina Zuniga

Research

The immune system is responsible for the tremendous task of fighting a wide range of pathogens to which we are constantly exposed. This system can be broadly subdivided into innate and adaptive arms, which act in conjunction to protect the host. The innate immune system exists in both vertebrate and invertebrate organisms and represents the first barrier against microbial invasion. This arm of the immune system rapidly eliminates the vast majority of microorganisms that we daily encounter and is responsible for limiting early pathogen replication and imprinting the profile of the subsequent adaptive response. The adaptive immune response is a more sophisticated feature, found only in vertebrate animals, involving a broad repertoire of genetically rearranged receptors that specifically recognize microbial antigens. The hallmark of the adaptive response is the generation of a potent and long-lasting protection specifically directed against the invading pathogen. Despite highly evolved immune responses, pathogens have co-evolved ways to evade or subvert the immune system and favor their replication and transmission. Therefore, despite major scientific and medical efforts, infectious diseases remain among the leading causes of mortality and disability worldwide.

Our laboratory uses a holistic perspective to study whole-organism, cellular and molecular aspects of immune responses during viral infections to determine general principles of antiviral immunity, immune-evasion, persistence and pathogenesis. We analyze both innate and adaptive immune responses, the multiple cells they entail and their interactions among themselves, with viruses and with non-immune-systems. This approach often situates our research at the boundaries of immunology and other disciplines, a challenge that we embrace in order to break new ground on the basic principles of antiviral immunity. The ultimate goal is to generate fundamental knowledge on immune-regulation that could help modulating immune responses to prevent or treat infectious diseases and possibly other immune-related illnesses.

As such, we have contributed to uncovering many fundamental aspects of Interferons, Dendritic Cells and T cells that extended beyond viral infections and broadened our general understanding of immune-regulation.

Some of the questions we are excited about include:

  1. What are the rules dictating whether an infection results in pathogen clearance versus persistence, host survival versus death, health recovery versus lasting sequels?
  2. How innate and adaptive immune cells adjust to co-exist with a foreign presence (i.e. persistent pathogen) during protracted infections, and what are the consequences of lacking such adaptations?
  3. How the immune system impacts and is impacted by other systems (e.g. gastro-intestinal system, central nervous system and whole-body metabolism) that should continue performing vital tasks while a host fights an infection, and how this cross-talk among different systems influence the infection outcome and disease?
  4. How multi-functional viral proteins exploit the cellular machinery to aid pathogen immune-evasion? Which are the specific pathways that they evolve to target and what are their implications for viral control and host health?

Select Publications

Full list on PubMed
  • Greene TT, Jo YR, Zuniga EI. Curr Opin Immunol. 2020 Oct;66:114-122. doi: 10.1016/j.coi.2020.08.001. Epub 2020 Sep 15. PMID: 32947131
  • Labarta-Bajo L, Gramalla-Schmitz A, Gerner RR, Kazane KR, Humphrey G, Schwartz T, Sanders K, Swafford A, Knight R, Raffatellu M, Zúñiga EI.Proc Natl Acad Sci U S A. 2020 Oct 6;117(40):24998-25007. doi: 10.1073/pnas.2003656117. Epub 2020 Sep 21.
  • Labarta-Bajo L, Nilsen SP, Humphrey G, Schwartz T, Sanders K, Swafford A, Knight R, Turner JR, Zúñiga EI.J Exp Med. 2020 Dec 7;217(12):e20192276. doi: 10.1084/jem.20192276.
  • Loureiro ME, Zorzetto-Fernandes AL, Radoshitzky S, Chi X, Dallari S, Marooki N, Lèger P, Foscaldi S, Harjono V, Sharma S, Zid BM, López N, de la Torre JC, Bavari S, Zuniga El. DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection. PLoS Pathog. 2018 Jul 12;14(7):e1007125. doi: 10.1371/journal.ppat.1007125
  • Macal M, Jo Y, Dallari S, Chang AY, Dai J, Swaminathan S, Wehrens EJ, Fitzgerald P, Zuniga EI. Self-Renewal and Toll-like Receptor Signaling Sustain Exhausted Plasmacytoid Dendritic Cells during Chronic Viral Infection. Immunity. 2018 Apr 17: 48(4):730-744.e5. doi:10.1016/j.immuni
  • Dallari S, Macal M, Loureiro ME, Jo Y, Swanson L, Hesser C, Ghosh P, Zuniga EI. Src Family Kinases Fyn and Lyn are Constitutively Activated and Mediate Plasmacytoid Dendritic Cell Responses. Nat Commun. 2017 Apr 3;8:14830. doi: 10.1038/ncomms14830.
  • Lewis GM, Wehrens EJ, Labarta-Bajo L, Streeck H, Zuniga EI. TGF-β Receptor Maintains CD4 T Helper Cell Identity during Chronic Viral Infections. J Cling Invest. 2016 Oct 3;126(10):3799-3813. doi: 10.1172/JCI87041.
  • Macal M, Tam MA, Hesser C, Di Domizio J, Leger P, Gilliet M, Zuniga EI. CD28 Deficiency Enhances Type I IFN Production by Murine Plasmacytoid Dendritic Cells. J Immunol. 2016 Feb 15;196(4):1900-9. doi: 10.4049/jimmunol.1501658.
  • Zuniga EI, Macal M, Lewis GM, Harker JA. Innate and Adaptive Immune Regulation During Chronic Viral Infections. Annu Rev Virol. 2015 Nov;2(1):573-97. doi: 10.1146/annurev-virology-100114-055226.
  • Harker JA, Wong KA, Dolgoter A, Zuniga EI. Cell-Intrinsic gp130 Signaling on CD4+ T Cells Shapes Long-Lasting Antiviral Immunity. J Immunol. 2015 Aug 1;195(3):1071-81. doi: 10.4049/jimmunol.1402402.
  • Harker JA, Dolgoter A, Zuniga EI. Cell-Intrinsic IL-27 and gp130 Cytokine Receptor Signaling Regulates Virus-Specific CD4+ T Cell Responses and Viral Control during Chronic Infection. Immunity. 2013 Sep 19;39(3):548-59. doi: 10.1016/j.immuni.2013.08.010.
  • Macal M, Lewis GM, Kunz S, Flavell R, Harker JA, Zuniga EI. Plasmacytoid Dendritic Cells are Productively Infected and Activated Through TLR-7 Early after Arenavirus Infection. Cell Host Microbe. 2012 Jun 14;11(6):617-30. doi: 10.1016/j.chom.2012.04.017.
  • Harker JA, Lewis GM, Mack L, Zuniga EI. Late interleukin-6 Escalates T Follicular Helper Cell Responses and Controls a Chronic Viral Infection. Science. 2011 Nov 11;334(6057):825-9. doi: 10.1126/science.1208421.
  • Tinoco R, Alcalde V, Yang Y, Sauer K, Zuniga EI. Cell-Intrinsic Transforming Growth Factor-β Signaling Mediates Virus-Specific CD8+ T Cell Deletion and Viral Persistence In Vivo. Immunity. 2009 Jul 17;31(1):145-57. doi: 10.1016/j.immuni.2009.06.015.
  • Zuniga EI, Liou LY, Mack L, Mendoza M, Oldstone MB. Persistent Virus Infection Inhibits Type I interferon Production by Plasmacytoid Dendritic Cells to Facilitate Opportunistic Infections. Cell Host Microbe. 2008 Oct 16;4(4):374-86. doi: 10.1016/j.chom.2008.08.016.
  • Lauterbach H, Zuniga EI, Truong P, Oldstone MB, McGavern DB. Adoptive Immunotherapy Induces CNS Dendritic Cell Recruitment and Antigen Presentation during Clearance of a Persistent Viral Infection. J Exp Med. 2006 Aug 7;203(8):1963-75. Epub 2006 Jul 17.
  • Zuniga EI, McGavern DB, Pruneda-Paz JL, Teng C, Oldstone MB. Bone Marrow Plasmacytoid Dendritic Cells can Differentiate into Myeloid Dendritic Cells upon Virus Infection. Nat Immunol. 2004 Dec;5(12):1227-34. Epub 2004 Nov 7.

Biography

Elina Zuniga received her Ph.D. in Biochemistry from the National University of Cordoba, Argentina. She conducted postdoctoral research at The Scripps Research Institute where she held two post-doctoral fellowships from Antorchas Foundation and PEW Charitable Trust. After joining UCSD in 2007 she has received a Hellman Foundation Scholar Award, The Vilcek Finalist Prize for Creative Promise, the Leukemia and Lymphoma Society Scholar Award and the American Cancer Society Scholar Award (a lifetime honor). Prof. Zuniga is also co-founder of Global Immunotalks and has been elected for the American Association of Immunologists Vanguard Lecture and for the American Academy of Microbiology Fellowship. She is stable member of the “Virology B” Study Section at the National Institute of Health as well as member of the American Association of Immunologists Fellowship Committee.

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