Back to Search
Start Over
A VP35 Mutant Ebola Virus Lacks Virulence but Can Elicit Protective Immunity to Wild-Type Virus Challenge.
- Source :
-
Cell reports [Cell Rep] 2019 Sep 17; Vol. 28 (12), pp. 3032-3046.e6. - Publication Year :
- 2019
-
Abstract
- Zaire ebolavirus (EBOV) VP35 protein is a suppressor of type I interferon (IFN) production, an inhibitor of dendritic cell maturation, and a putative virulence determinant. Here, a recombinant EBOV encoding a mutant VP35 virus (VP35m) is demonstrated to activate RIG-I-like receptor signaling and innate antiviral pathways. When inoculated into cynomolgus macaques, VP35m exhibits dramatic attenuation as compared to wild-type EBOV (wtEBOV), with 20 or 300 times the standard 100% lethal challenge dose not causing EBOV disease (EVD). Further, VP35m infection, despite limited replication in vivo, activates antigen presentation and innate immunity pathways and elicits increased frequencies of proliferating memory T cells and B cells and production of anti-EBOV antibodies. Upon wtEBOV challenge, VP35m-immunized animals survive, exhibiting host responses consistent with an orderly immune response and the absence of excessive inflammation. These data demonstrate that VP35 is a critical EBOV immune evasion factor and provide insights into immune mechanisms of EBOV control.<br /> (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Chlorocebus aethiops
Macaca fascicularis
Vero Cells
B-Lymphocytes immunology
B-Lymphocytes pathology
Ebolavirus genetics
Ebolavirus immunology
Ebolavirus pathogenicity
Hemorrhagic Fever, Ebola genetics
Hemorrhagic Fever, Ebola immunology
Hemorrhagic Fever, Ebola pathology
Hemorrhagic Fever, Ebola prevention & control
T-Lymphocytes immunology
T-Lymphocytes pathology
Viral Regulatory and Accessory Proteins genetics
Viral Regulatory and Accessory Proteins immunology
Virulence Factors genetics
Virulence Factors immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 28
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 31533029
- Full Text :
- https://doi.org/10.1016/j.celrep.2019.08.047