Systemic viral spreading and defective host responses are associated with fatal Lassa fever in macaques

被引：27

作者：

Baillet, Nicolas ^{[1
,2
]}

Reynard, Stephanie ^{[1
,2
]}

Perthame, Emeline ^{[3
]}

Hortion, Jimmy ^{[1
,2
]}

Journeaux, Alexandra ^{[1
,2
]}

Mateo, Mathieu ^{[1
,2
]}

Carnec, Xavier ^{[1
,2
]}

Schaeffer, Justine ^{[1
,2
]}

Picard, Caroline ^{[1
,2
]}

Barrot, Laura ^{[4
]}

Barron, Stephane ^{[4
]}

Vallve, Audrey ^{[4
]}

Duthey, Aurelie ^{[4
]}

Jacquot, Frederic ^{[4
]}

Boehringer, Cathy ^{[4
]}

Jouvion, Gregory ^{[5
]}

Pietrosemoli, Natalia ^{[3
]}

Legendre, Rachel ^{[3
]}

Dillies, Marie-Agnes ^{[3
]}

Allan, Richard ^{[6
]}

Legras-Lachuer, Catherine ^{[6
]}

Carbonnelle, Caroline ^{[4
]}

Raoul, Herve ^{[4
]}

Baize, Sylvain ^{[1
,2
]}

机构：

[1] Inst Pasteur, Unite Biol Infect Virales Emergentes, Lyon, France

[2] Univ Lyon 1, Ctr Int Rech Infectiol CIRI, Ecole Normale Super Lyon, Univ Lyon,INSERM U1111,CNRS UMR5308, Lyon, France

[3] Inst Pasteur, USR CNRS 3756, Hub Bioinformat & Biostat, Dept Biol Computationnelle, Paris, France

[4] Lab P4 INSERM Jean Merieux, INSERM US003, Lyon, France

[5] Inst Pasteur, Dept Sante Globale, Neuropathol Expt, Paris, France

[6] ViroScan3D SAS, Trevoux, France

来源：

COMMUNICATIONS BIOLOGY | 2021年 / 4卷 / 01期

关键词：

FIBROBLASTIC RETICULAR CELLS; HUMAN DENDRITIC CELLS; VIRUS-INFECTION; IMMUNE-RESPONSE; MOPEIA VIRUS; SEPSIS; CD4(+); MODEL; ACTIVATION; EXPRESSION;

D O I：

10.1038/s42003-020-01543-7

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Lassa virus (LASV) is endemic in West Africa and induces a viral hemorrhagic fever (VHF) with up to 30% lethality among clinical cases. The mechanisms involved in control of Lassa fever or, in contrast, the ensuing catastrophic illness and death are poorly understood. We used the cynomolgus monkey model to reproduce the human disease with asymptomatic to mild or fatal disease. After initial replication at the inoculation site, LASV reached the secondary lymphoid organs. LASV did not spread further in nonfatal disease and was rapidly controlled by balanced innate and T-cell responses. Systemic viral dissemination occurred during severe disease. Massive replication, a cytokine/chemokine storm, defective T-cell responses, and multiorgan failure were observed. Clinical, biological, immunological, and transcriptomic parameters resembled those observed during septic-shock syndrome, suggesting that similar pathogenesis is induced during Lassa fever. The outcome appears to be determined early, as differentially expressed genes in PBMCs were associated with fatal and non-fatal Lassa fever outcome very early after infection. These results provide a full characterization and important insights into Lassa fever pathogenesis and could help to develop early diagnostic tools. Baillet et al. use the cynomolgus monkey model to model Lassa virus and associated Lassa fever (LF). They provide a full characterisation of LF pathogenesis with the aim of assisting the development of early diagnostic tools.

引用

页数：19

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