Long-term Sudan Virus Ebola Survivors Maintain Multiple Antiviral Defense Mechanisms

Author:

Sobarzo Ariel12,Moné Yves3,Lang Steven3,Gelkop Sigal1,Brangel Polina4,Kuehne Ana I5,McKendry Rachel A4,Mell Joshua Chang3,Ahmed Azad3,Davis Claytus1,Dye John M5,Lutwama Julius Julian6,Lobel Leslie1,Veas Francisco78,Ehrlich Garth D3ORCID

Affiliation:

1. The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva , Israel

2. The Pre-Clinical Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev , Beer-Sheva , Israel

3. Department of Microbiology and Immunology, Center for Genomic Sciences and Center for Advanced Microbial Processing, Institute for Molecular Medicine and Infectious Disease, Genomic Core Facility, Drexel University College of Medicine , Philadelphia, Pennsylvania , USA

4. London Centre for Nanotechnology, Division of Medicine, University College London , London , United Kingdom

5. Viral Immunology Branch, US Army Medical Research Institute of Infectious Diseases , Fort Detrick, Maryland , USA

6. Department of Arbovirology, Emerging and Re-emerging Infection, Uganda Virus Research Institute , Entebbe , Uganda

7. Molecular Comparative Immuno-Physiopathology Lab, French Institute of Research for Development Health Branch of UMR5151 and UMR Research Unit-Ministry of Defense, Faculty of Pharmacy, University of Montpellier , Montpellier , France

8. Copernicus Integrated Solutions for Biosafety Risks, Faculty of Pharmacy, Montpellier University Montpellier , France

Abstract

Abstract Background The critical issues of sustained memory immunity following ebolavirus disease among long-term survivors are still unclear. Methods Here, we examine virus-specific immune and inflammatory responses following in vitro challengd in 12 Sudan virus (SUDV) long-term survivors from Uganda’s 2000–2001 Gulu outbreak, 15 years after recovery. Total RNA from isolated SUDV-stimulated and unstimulated peripheral blood mononuclear cells was extracted and analyzed. Matched serum samples were also collected to determine SUDV IgG levels and functionality. Results We detected persistent humoral (58%, 7 of 12) and cellular (33%, 4 of 12) immune responses in SUDV long-term survivors and identified critical molecular mechanisms of innate and adaptive immunity. Gene expression in immune pathways, the interferon signaling system, antiviral defense response, and activation and regulation of T- and B-cell responses were observed. SUDV long-term survivors also maintained robust virus-specific IgG antibodies capable of polyfunctional responses, including neutralizing and innate Fc effector functions. Conclusions Data integration identified significant correlations among humoral and cellular immune responses and pinpointed a specific innate and adaptive gene expression signature associated with long-lasting immunity. This could help identify natural and vaccine correlates of protection against ebolavirus disease.

Funder

European Commission

Drexel University

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

Reference49 articles.

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1. Harnessing high-throughput OMICS in emerging zoonotic virus preparedness and response activities;Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease;2024-10

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