Pathological and immunological characterization of bluetongue virus serotype 1 infection in type I interferons blocked immunocompetent adult mice
| Autor: | Jyoti Misri, S. Vineetha, Mani Saminathan, Yashpal Singh Malik, Madhulina Maity, Gundallhalli Bayyappa Manjunathareddy, Vivek Kumar Gupta, Kuldeep Dhama, Karam Pal Singh, Muthannan Andavar Ramakrishnan |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Medicine (General) Science (General) Leukocytosis Pharmaceutical Science Apoptosis Receptor Interferon alpha-beta Immune responses Bluetongue virus serotype 1 Pathogenesis Q1-390 Mice 0302 clinical medicine Interferon Type I IFNs blockade Leukocytes Lung Multidisciplinary MAR1-5A3 antibody Lymphatic system medicine.anatomical_structure 030220 oncology & carcinogenesis Interferon Type I Female medicine.drug Spleen Biology Serogroup Bluetongue Virus 03 medical and health sciences R5-920 Immune system Antigen medicine Animals Antibodies Blocking Sequential pathology ComputingMethodologies_COMPUTERGRAPHICS Sheep Models Immunological Viral Vaccines Adult mouse Leukopenia 030104 developmental biology Immunology Lymph Nodes Bluetongue virus CD8 |
| Zdroj: | Journal of Advanced Research Journal of Advanced Research, Vol 31, Iss, Pp 137-153 (2021) |
| ISSN: | 2090-1232 |
| DOI: | 10.1016/j.jare.2021.01.007 |
| Popis: | Graphical abstract Introduction Wild-type adult mice with intact interferon (IFN) system were neither susceptible to bluetongue virus (BTV) infection nor showed signs of morbidity/mortality. Establishment of immunologically competent wild-type adult mouse model with type I IFNs blockade is necessary to assess the pathogenesis, immune responses and testing of BTV vaccines. Objectives Present study aimed to establish and characterize BTV serotype 1 infection in immunocompetent adult mice with type I IFNs blockade at the time of infection by studying immune responses and sequential pathology. Methods Adult mice were administered with anti-mouse IFN-α/β receptor subunit-1 (IFNAR1) blocking antibody (Clone: MAR1-5A3) 24 h before and after BTV serotype 1 infection, and sacrificed at various time points. Sequential pathology, BTV localization by immunohistochemistry and quantification by qRT-PCR, immune cell kinetics and apoptosis by flow cytometry, and cytokines estimation by c-ELISA and qRT-PCR were studied. Results IFNAR blocked-infected mice developed clinical signs and typical lesions of BT; whereas, isotype-infected control mice did not develop any disease. The IFNAR blocked-infected mice showed enlarged, edematous, and congested lymph nodes (LNs) and spleen, and vascular (congestion and hemorrhage) and pneumonic lesions in lungs. Histopathologically, marked lymphoid depletion with “starry-sky pattern” due to lymphocytes apoptosis was noticed in the LNs and spleen. BTV antigen was detected and quantified in lymphoid organs, lungs, and other organs at various time points. Initial leukopenia (increased CD4+/CD8+ T cells ratio) followed by leukocytosis (decreased CD4+/CD8+ T cells ratio) and significantly increased biochemical values were noticed in IFNAR blocked-infected mice. Increased apoptotic cells in PBMCs and tissues coincided with viral load and levels of different cytokines in blood, spleen and draining LNs and notably varied between time points in IFNAR blocked-infected mice. Conclusion Present study is first to characterize BTV serotype 1 infection in immunocompetent adult mouse with type I IFNs blockade. The findings will be useful for studying pathogenesis and testing the efficacy of BTV vaccines. |
| Databáze: | OpenAIRE |
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