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

doi:10.1016/j.celrep.2024.113706

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

Cell Rep. 2024 Feb 27;43(2):113706. doi: 10.1016/j.celrep.2024.113706. Epub 2024 Jan 30.

Authors

Kalani Ratnasiri¹, Hong Zheng², Jiaying Toh³, Zhiyuan Yao⁴, Veronica Duran⁴, Michele Donato⁵, Mario Roederer⁶, Megha Kamath⁶, John-Paul M Todd⁶, Matthew Gagne⁶, Kathryn E Foulds⁶, Joseph R Francica⁶, Kizzmekia S Corbett⁶, Daniel C Douek⁶, Robert A Seder⁶, Shirit Einav⁷, Catherine A Blish⁸, Purvesh Khatri⁹

Affiliations

¹ Stanford Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Epidemiology and Population Health, Stanford University, Stanford, CA 94305, USA.
² 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.
³ 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.
⁴ Department of Microbiology and Immunology, Stanford University, CA 94305, USA.
⁵ 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.
⁶ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁷ 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.
⁸ 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.
⁹ 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. Electronic address: pkhatri@stanford.edu.

Abstract

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.

Keywords: CP: Immunology; antiviral immunity; conserved host response to viruses; human immune response; macaques; non-human primates; systems immunology; transcriptomics; virus.

MeSH terms

Animals
Antiviral Agents
Filoviridae*
Humans
Immunoinformatics
Macaca
Orthomyxoviridae Infections*

Substances

Antiviral Agents

Abstract

MeSH terms

Substances

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