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
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.
