Venezuelan equine encephalitis virus infection causes modulation of inflammatory and immune response genes in mouse brain.
BACKGROUND
Neurovirulent Venezuelan equine encephalitis virus (VEEV) causes lethal encephalitis in equines and is transmitted to humans by mosquitoes. VEEV is highly infectious when transmitted by aerosol and has been developed as a bio-warfare agent, making it an important pathogen to study from a military and civilian standpoint. Molecular mechanisms of VEE pathogenesis are poorly understood. To study these, the gene expression profile of VEEV infected mouse brains was investigated. Changes in gene expression were correlated with histological changes in the brain. In addition, a molecular framework of changes in gene expression associated with progression of the disease was studied.


RESULTS
Our results demonstrate that genes related to important immune pathways such as antigen presentation, inflammation, apoptosis and response to virus (Cxcl10, CxCl11, Ccl5, Ifr7, Ifi27 Oas1b, Fcerg1,Mif, Clusterin and MHC class II) were upregulated as a result of virus infection. The number of over-expressed genes (>1.5-fold level) increased as the disease progressed (from 197, 296, 400, to 1086 at 24, 48, 72 and 96 hours post infection, respectively).


CONCLUSIONS
Identification of differentially expressed genes in brain will help in the understanding of VEEV-induced pathogenesis and selection of biomarkers for diagnosis and targeted therapy of VEEV-induced neurodegeneration.
Centre for Combat Casualty and Life Sustainment Research, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. asharma@usuhs.mil
Anuj
A
Sharma
Bhaskar
B
Bhattacharya
Raj K
RK
Puri
Radha K
RK
Maheshwari
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000941:Antigens / Q000276:immunology; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004685:Encephalomyelitis, Venezuelan Equine / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D004801:Eosine Yellowish-(YS) / Q000378:metabolism; D020869:Gene Expression Profiling; D006416:Hematoxylin / Q000378:metabolism; D007109:Immunity / Q000235:genetics*; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics*; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D000941:Antigens; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin