Journal Article

Fatal Lassa fever in cynomolgus monkeys is associated with systemic viral dissemination and inflammation

Germain, Clara, Journeaux, Alexandra, Lopez-Maestre, Hélène, Perthame, Emeline, Legras-Lachuer, Catherine, Hortion, Jimmy, Reynard, Stéphanie, Croze, Séverine, Baize, Sylvain, Lafoux, Blaise, Soyer, Laura, Baillet, Nicolas, Pietrosemoli, Natalia, Rey, Catherine

2024

Overview

The pathogenesis of Lassa fever has not yet been fully deciphered, particularly as concerns the mechanisms determining whether acute infection is controlled or leads to catastrophic illness and death. Using a cynomolgus monkey model of Lassa virus (LASV) infection reproducing the different outcomes of the disease, we performed histological and transcriptomic studies to investigate the dynamics of LASV infection and the immune mechanisms associated with survival or death. Lymphoid organs are an early major reservoir for replicating virus during Lassa fever, with LASV entering through the cortical sinus of draining lymph nodes regardless of disease outcome. However, subsequent viral tropism varies considerably with disease severity, with viral dissemination limited almost entirely to lymphoid organs and immune cells during nonfatal Lassa fever. By contrast, the systemic dissemination of LASV to all organs and diverse cell types, leading to infiltrations with macrophages and neutrophils and an excessive inflammatory response, is associated with a fatal outcome. These results provide new insight into early viral dynamics and the host response to LASV infection according to disease outcome.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adrenal glands / Animal biology / Animals / Antigens / Biochemistry, Molecular Biology / Biology and Life Sciences / Disease Models, Animal / Disease transmission / Epidemics / Fever / Genomics / Human health and pathology / Immune system / Immunology / Infections / Infectious diseases / Inflammation / Inflammation - immunology / Inflammation - virology / Inflammatory response / Innate immunity / Lassa fever / Lassa Fever - immunology / Lassa Fever - pathology / Lassa Fever - virology / Lassa virus - immunology / Lassa virus - pathogenicity / Leukocytes (neutrophilic) / Life Sciences / Lymph nodes / Macaca fascicularis / Macrophages / Male / Medical research / Medicine and Health Sciences / Medicine, Experimental / Microbiology and Parasitology / Monkeys / Organs / Pathogenesis / Patients / Physiological aspects / Transcriptomics / Tropism / Veterinary medicine and animal Health / Viral Tropism / Virology / Viruses