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Publications

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural Epublish 7 citations

PubMed: 36569838 DOI: 10.3389/fimmu.2022.1012824

Longitudinal serum proteomics analyses identify unique and overlapping host response pathways in Lyme disease and West Nile virus infection.

Front Immunol 13:1012824

Authors: Patrick Boada, Benoit Fatou, Alexia A Belperron, Tara K Sigdel, Kinga K Smolen, Zainab Wurie, Ofer Levy, Shannon E Ronca, Kristy O Murray, Juliane M Liberto, Priyanka Rashmi, Maggie Kerwin, Ruth R Montgomery, Linda K Bockenstedt, Hanno Steen, Minnie M Sarwal

Affiliations

  • Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, CA, United States.
  • Department of Pathology, Boston Children's Hospital - Harvard Medical School, Boston, MA, United States.
  • Precision Vaccines Program, Boston Children's Hospital, Boston, MA, United States.
  • Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
  • Division of Infectious Diseases, Boston Children's Hospital - Harvard Medical School, Boston, MA, United States.
  • Department of Pathology, Boston Children's Hospital - Harvard Medical School, Boston, MA, United States. Precision Vaccines Program, Boston Children's Hospital, Boston, MA, United States.
  • Broad Institute of Massachusetts Institute of Technology & Harvard, Cambridge, MA, United States.
  • Division of Tropical Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States.
  • William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston, TX, United States.

Abstract

Advancement in proteomics methods for interrogating biological samples has helped identify disease biomarkers for early diagnostics and unravel underlying molecular mechanisms of disease. Herein, we examined the serum proteomes of 23 study participants presenting with one of two common arthropod-borne infections: Lyme disease (LD), an extracellular bacterial infection or West Nile virus infection (WNV), an intracellular viral infection. The LC/MS based serum proteomes of samples collected at the time of diagnosis and during convalescence were assessed using a depletion-based high-throughput shotgun proteomics (dHSP) pipeline as well as a non-depleting blotting-based low-throughput platform (MStern). The LC/MS integrated analyses identified host proteome responses in the acute and recovery phases shared by LD and WNV infections, as well as differentially abundant proteins that were unique to each infection. Notably, we also detected proteins that distinguished localized from disseminated LD and asymptomatic from symptomatic WNV infection. The proteins detected in both diseases with the dHSP pipeline identified unique and overlapping proteins detected with the non-depleting MStern platform, supporting the utility of both detection methods. Machine learning confirmed the use of the serum proteome to distinguish the infection from healthy control sera but could not develop discriminatory models between LD and WNV at current sample numbers. Our study is the first to compare the serum proteomes in two arthropod-borne infections and highlights the similarities in host responses even though the pathogens and the vectors themselves are different.

MeSH

West Nile Fever, Serum, Lyme Disease, West Nile Virus, Asymptomatic Infections, Immune System Diseases, Viruses, Proteomics, Proteome, Acute-Phase Reaction, Virus Diseases

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