Longitudinal analysis of immunocyte responses and inflammatory cytokine profiles in SFTSV-infected rhesus macaques

Yi-Hui Li; Wen-Wu Huang; Wen-Qiang He; Xiao-Yan He; Xue-Hui Wang; Ya-Long Lin; Zu-Jiang Zhao; Yong-Tang Zheng; Wei Pang

doi:10.3389/fimmu.2023.1143796

Longitudinal analysis of immunocyte responses and inflammatory cytokine profiles in SFTSV-infected rhesus macaques

Front Immunol. 2023 Mar 22:14:1143796. doi: 10.3389/fimmu.2023.1143796. eCollection 2023.

Authors

Yi-Hui Li^{1

2}, Wen-Wu Huang^{1

2

3}, Wen-Qiang He^{1

2}, Xiao-Yan He^{1

2}, Xue-Hui Wang^{1

4}, Ya-Long Lin^{1

2}, Zu-Jiang Zhao^{1

2}, Yong-Tang Zheng^{1

2}, Wei Pang^{1

2}

Affiliations

¹ Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology - The Chinese University of Hong Kong (KIZ-CUHK) Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
² Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
³ Office of Science and Technology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
⁴ School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging bunyavirus, causes severe fever with thrombocytopenia syndrome (SFTS), with a high fatality rate of 20%-30%. At present, however, the pathogenesis of SFTSV remains largely unclear and no specific therapeutics or vaccines against its infection are currently available. Therefore, animal models that can faithfully recapitulate human disease are important to help understand and treat SFTSV infection. Here, we infected seven Chinese rhesus macaques (Macaca mulatta) with SFTSV. Virological and immunological changes were monitored over 28 days post-infection. Results showed that mild symptoms appeared in the macaques, including slight fever, thrombocytopenia, leukocytopenia, increased aspartate aminotransferase (AST) and creatine kinase (CK) in the blood. Viral replication was persistently detectable in lymphoid tissues and bone marrow even after viremia disappeared. Immunocyte detection showed that the number of T cells (mainly CD8⁺ T cells), B cells, natural killer (NK) cells, and monocytes decreased during infection. In detail, effector memory CD8⁺ T cells declined but showed increased activation, while both the number and activation of effector memory CD4⁺ T cells increased significantly. Furthermore, activated memory B cells decreased, while CD80⁺/CD86⁺ B cells and resting memory B cells (CD27⁺CD21⁺) increased significantly. Intermediate monocytes (CD14⁺CD16⁺) increased, while myeloid dendritic cells (mDCs) rather than plasmacytoid dendritic cells (pDCs) markedly declined during early infection. Cytokines, including interleukin-6 (IL-6), interferon-inducible protein-10 (IP-10), and macrophage inflammatory protein 1 (MCP-1), were substantially elevated in blood and were correlated with activated CD4⁺ T cells, B cells, CD16⁺CD56⁺ NK cells, CD14⁺CD16⁺ monocytes during infection. Thus, this study demonstrates that Chinese rhesus macaques infected with SFTSV resemble mild clinical symptoms of human SFTS and provides detailed virological and immunological parameters in macaques for understanding the pathogenesis of SFTSV infection.

Keywords: SFTSV; immunocyte subsets; inflammatory cytokines; non-human primates; rhesus macaques.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes
Cytokines
Humans
Macaca mulatta
Phlebovirus*
Severe Fever with Thrombocytopenia Syndrome*

Substances

Cytokines

Grants and funding

This work was supported in part by grants from the National Key R & D Program of China (2021YFC2301700, 2018ZX10301406), Yunnan Key R & D Program (202103AQ100001, 202103AC100005), the Yunnan Major Science and Technique Programs (202102AA310055), the key program of Chinese Academy of Sciences (KJZD-SW-L11-02), and CAS “Light of West China”.