Dataset Information

Identification of genes involved in the host response to neurovirulent alphavirus infection.

ABSTRACT: Single-amino-acid mutations in Sindbis virus proteins can convert clinically silent encephalitis into uniformly lethal disease. However, little is known about the host gene response during avirulent and virulent central nervous system (CNS) infections. To identify candidate host genes that modulate alphavirus neurovirulence, we utilized GeneChip Expression analysis to compare CNS gene expression in mice infected with two strains of Sindbis virus that differ by one amino acid in the E2 envelope glycoprotein. Infection with Sindbis virus, dsTE12H (E2-55 HIS), resulted in 100% mortality in 10-day-old mice, whereas no disease was observed in mice infected with dsTE12Q (E2-55 GLN). dsTE12H, compared with dsTE12Q, replicated to higher titers in mouse brain and induced more CNS apoptosis. Infection with the neurovirulent dsTE12H strain was associated with both a greater number of host genes with increased expression and greater changes in levels of host gene expression than was infection with the nonvirulent dsTE12Q strain. In particular, dsTE12H infection resulted in greater increases in the levels of mRNAs encoding chemokines, proteins involved in antigen presentation and protein degradation, complement proteins, interferon-regulated proteins, and mitochondrial proteins. At least some of these increases may be beneficial for the host, as evidenced by the demonstration that enforced expression of the antiapoptotic mitochondrial protein peripheral benzodiazepine receptor (PBR) protects neonatal mice against lethal Sindbis virus infection. Thus, our findings identify specific host genes that may play a role in the host protective or pathologic response to neurovirulent Sindbis virus infection.

SUBMITTER: Johnston C

PROVIDER: S-EPMC114617 | biostudies-literature | 2001 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of genes involved in the host response to neurovirulent alphavirus infection.

Johnston C C Jiang W W Chu T T Levine B B

Journal of virology 20011101 21

Single-amino-acid mutations in Sindbis virus proteins can convert clinically silent encephalitis into uniformly lethal disease. However, little is known about the host gene response during avirulent and virulent central nervous system (CNS) infections. To identify candidate host genes that modulate alphavirus neurovirulence, we utilized GeneChip Expression analysis to compare CNS gene expression in mice infected with two strains of Sindbis virus that differ by one amino acid in the E2 envelope g ...[more]

PMID: 11581411

Similar Datasets

Project description:Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae. VEEV causes a bi-phasic illness in mice where primary replication in lymphoid organs is followed by entry into the central nervous system (CNS). The CNS phase of infection is marked by encephalitis and large scale neuronal death ultimately resulting in death. Molecular determinants of VEEV neurovirulence are not well understood. In this study, host gene expression response to highly neurovirulent VEEV (V3000 strain) infection was compared with that of a partially neurovirulent VEEV (V3034 strain) to identify host factors associated with VEEV neurovirulence.Whole genome microarrays were performed to identify the significantly modulated genes. Microarray observations were classified into three categories i.e., genes that were similarly modulated against both V3000 and V3034 infections, and genes that were uniquely modulated in infection with V3034 or V3000. Histologic sections of spleen and brain were evaluated by hematoxylin and eosin stains from all the mice.V3000 infection induced a greater degree of pathology in both the spleen and brain tissue of infected mice compared to V3034 infection. Genes commonly modulated in the spleens after V3000 or V3034 infection were associated with innate immune responses, inflammation and antigen presentation, however, V3000 induced a gene response profile that suggests a stronger inflammatory and apoptotic response compared to V3034. In the brain, both the strains of VEEV induced an innate immune response reflected by an upregulation of the genes involved in antigen presentation, interferon response, and inflammation. Similar to the spleen, V3000 was found to induce a stronger inflammatory response than V3034 in terms of induction of pro-inflammatory genes and associated pathways. Ccl2, Ccl5, Ccl6, and Ly6 were uniquely upregulated in V3000 infected mouse brains and correlated with the extensive inflammation observed in the brain.The common gene profile identified from V3000 and V3034 exposure can help in understanding a generalized host response to VEEV infection. Inflammatory genes that were uniquely identified in mouse brains with V3000 infection will help in better understanding the lethal neurovirulence of VEEV. Future studies are needed to explore the roles played by the genes identified in VEEV induced encephalitis.

Project description:BackgroundMastitis in dairy cattle results from infection of mammary tissue by a range of micro-organisms but principally coliform bacteria and Gram positive bacteria such as Staphylococcus aureus. The former species are often acquired by environmental contamination while S. aureus is particularly problematic due to its resistance to antibiotic treatments and ability to reside within mammary tissue in a chronic, subclinical state. The transcriptional responses within bovine mammary epithelial tissue subjected to intramammary challenge with S. aureus are poorly characterised, particularly at the earliest stages of infection. Moreover, the effect of infection on the presence of bioactive innate immune proteins in milk is also unclear. The nature of these responses may determine the susceptibility of the tissue and its ability to resolve the infection.ResultsTranscriptional profiling was employed to measure changes in gene expression occurring in bovine mammary tissues sampled from three dairy cows after brief and graded intramammary challenges with S. aureus. These limited challenges had no significant effect on the expression pattern of the gene encoding beta-casein but caused coordinated up-regulation of a number of cytokines and chemokines involved in pro-inflammatory responses. In addition, the enhanced expression of two genes, S100 calcium-binding protein A12 (S100A12) and Pentraxin-3 (PTX3) corresponded with significantly increased levels of their proteins in milk from infected udders. Both genes were shown to be expressed by mammary epithelial cells grown in culture after stimulation with lipopolysaccharide. There was also a strong correlation between somatic cell count, a widely used measure of mastitis, and the level of S100A12 in milk from a herd of dairy cows. Recombinant S100A12 inhibited growth of Escherichia coli in vitro and recombinant PTX3 bound to E. coli as well as C1q, a subunit of the first component of the complement cascade.ConclusionThe transcriptional responses in infected bovine mammary tissue, even at low doses of bacteria and short periods of infection, probably reflect the combined contributions of gene expression changes resulting from the activation of mammary epithelial cells and infiltrating immune cells. The secretion of a number of proinflammatory cytokines and chemokines from mammary epithelial cells stimulated by the bacteria serves to trigger the recruitment and activation of neutrophils in mammary tissue. The presence of S100A12 and PTX3 in milk from infected udder quarters may increase the anti-bacterial properties of milk thereby helping to resolve the mammary tissue infection as well as potentially contributing to the maturation of the newborn calf epithelium and establishment of the newborn gut microbial population.

Dataset Information

Identification of genes involved in the host response to neurovirulent alphavirus infection.

Publications

Identification of genes involved in the host response to neurovirulent alphavirus infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets