Systems immunology of transcriptional responses to viral infection identifies conserved antiviral pathways across macaques and humans

Kalani Ratnasiri; Hong Zheng; Jiaying Toh; Zhiyuan Yao; Veronica Duran; Michele Donato; Mario Roederer; Megha Kamath; John-Paul M. Todd; Matthew Gagne; Kathryn E. Foulds; Joseph R. Francica; Kizzmekia S. Corbett; Daniel C. Douek; Robert A. Seder; Shirit Einav; Catherine A. Blish; Purvesh Khatri

Cell Reports (Feb 2024)

Systems immunology of transcriptional responses to viral infection identifies conserved antiviral pathways across macaques and humans

Kalani Ratnasiri,
Hong Zheng,
Jiaying Toh,
Zhiyuan Yao,
Veronica Duran,
Michele Donato,
Mario Roederer,
Megha Kamath,
John-Paul M. Todd,
Matthew Gagne,
Kathryn E. Foulds,
Joseph R. Francica,
Kizzmekia S. Corbett,
Daniel C. Douek,
Robert A. Seder,
Shirit Einav,
Catherine A. Blish,
Purvesh Khatri

Affiliations

Kalani Ratnasiri: Stanford Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Epidemiology and Population Health, Stanford University, Stanford, CA 94305, USA
Hong Zheng: Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA
Jiaying Toh: Stanford Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA 94305, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA
Zhiyuan Yao: Department of Microbiology and Immunology, Stanford University, CA 94305, USA
Veronica Duran: Department of Microbiology and Immunology, Stanford University, CA 94305, USA
Michele Donato: Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA 94305, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA
Mario Roederer: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Megha Kamath: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
John-Paul M. Todd: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Matthew Gagne: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Kathryn E. Foulds: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Joseph R. Francica: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Kizzmekia S. Corbett: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Daniel C. Douek: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Robert A. Seder: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Shirit Einav: Department of Microbiology and Immunology, Stanford University, CA 94305, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA
Catherine A. Blish: Stanford Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA
Purvesh Khatri: Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA 94305, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA 94305, USA; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 2
p. 113706

Abstract

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Summary: Viral pandemics and epidemics pose a significant global threat. While macaque models of viral disease are routinely used, it remains unclear how conserved antiviral responses are between macaques and humans. Therefore, we conducted a cross-species analysis of transcriptomic data from over 6,088 blood samples from macaques and humans infected with one of 31 viruses. Our findings demonstrate that irrespective of primate or viral species, there are conserved antiviral responses that are consistent across infection phase (acute, chronic, or latent) and viral genome type (DNA or RNA viruses). Leveraging longitudinal data from experimental challenges, we identify virus-specific response kinetics such as host responses to Coronaviridae and Orthomyxoviridae infections peaking 1–3 days earlier than responses to Filoviridae and Arenaviridae viral infections. Our results underscore macaque studies as a powerful tool for understanding viral pathogenesis and immune responses that translate to humans, with implications for viral therapeutic development and pandemic preparedness.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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