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Systems analysis of subjects acutely infected with the Chikungunya virus
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP, PLoS Pathogens, PLoS Pathogens, Vol 15, Iss 6, p e1007880 (2019)
- Publication Year :
- 2019
-
Abstract
- The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.<br />Author summary The Chikungunya virus (CHIKV) has infected millions of people worldwide and presents a serious public health issue. Acute symptomatic infections caused by contracting this mosquito-transmitted arbovirus are typically associated with an abrupt onset of fever and often debilitating polyarthralgia/ polyarthritis, as well as prolonged periods of disability in some patients. These dramatic effects call for a careful evaluation of the molecular mechanisms involved in this puzzling infection. By analyzing the blood transcriptome of adults acutely infected with CHIKV, we were able to provide a detailed picture of the early molecular events induced by the infection. Additionally, the systems biology approach revealed genes that can be investigated extensively as probable therapeutic targets for the disease.
- Subjects :
- RNA viruses
Viral Diseases
Apolipoprotein B
Physiology
Inflammasomes
Interleukin-1beta
Gene Identification and Analysis
Genetic Networks
Dengue virus
medicine.disease_cause
Pathology and Laboratory Medicine
Virus Replication
Biochemistry
Mice
Eukaryotic initiation factor
Medicine and Health Sciences
Chikungunya
Biology (General)
0303 health sciences
Chikungunya Virus
Immune System Proteins
biology
030302 biochemistry & molecular biology
virus diseases
Inflammasome
Genomics
Body Fluids
Infectious Diseases
Blood
Medical Microbiology
Arboviral Infections
Viral Pathogens
Viruses
Polyarthritis
Female
Pathogens
Anatomy
Transcriptome Analysis
Network Analysis
medicine.drug
Research Article
Neglected Tropical Diseases
Adult
Computer and Information Sciences
Fever
QH301-705.5
Alphaviruses
Immunology
Rheumatoid Arthritis
Microbiology
Virus
Autoimmune Diseases
Togaviruses
03 medical and health sciences
Rheumatology
Virology
Cytidine Deaminase
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Genetics
Animals
Humans
Molecular Biology
Gene
Microbial Pathogens
030304 developmental biology
Biology and life sciences
Arthritis
Organisms
Chikungunya Infection
Computational Biology
Proteins
MICROBIOLOGIA
RC581-607
Dengue Virus
medicine.disease
Tropical Diseases
Genome Analysis
biology.protein
Chikungunya Fever
Parasitology
Clinical Immunology
Immunologic diseases. Allergy
Clinical Medicine
Follow-Up Studies
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP, PLoS Pathogens, PLoS Pathogens, Vol 15, Iss 6, p e1007880 (2019)
- Accession number :
- edsair.doi.dedup.....7ef9cb870a14a64254f57ca88381c21c