Biomedical subjects

Raj Deonarain

Publications and source records attributed to Raj Deonarain.

3 recordsLinked to original sources

PubMed2004

Protective role for interferon-beta in coxsackievirus B3 infection.

BACKGROUND: Coxsackievirus-induced myocarditis can be a serious cause of heart failure. In the absence of a specific antiviral therapy, modulating the host immune response may be protective. Interferons (IFNs)-alpha and -beta perform a fundamental role in innate and adaptive antiviral responses, thereby presenting as candidate therapeutics for coxsackievirus infections. METHODS AND RESULTS: To examine the contribution of IFN-beta in protection from coxsackievirus B3 (CVB3) infection, mice lacking the IFN-beta gene were infected with 10(3) plaque-forming units of CVB3. In contrast to wild-type mice that exhibit an intact IFN-beta response, we observed increased susceptibility to infection (70% mortality), a downregulation of IFN-stimulated gene targets (2'-5' oligoadenylate synthetase, serine/threonine protein kinase, the GTPase Mx), and cardiomyocyte breakdown and disruption in the IFN-beta-/- mice. CONCLUSIONS: Viewed together, these results clearly demonstrate that IFN-beta is important in mediating protection against CVB3-induced myocarditis.

2',5'-Oligoadenylate Synthetase↗

PubMed2003

Critical roles for IFN-beta in lymphoid development, myelopoiesis, and tumor development: links to tumor necrosis factor alpha.

We have generated mice null for IFN-beta and report the diverse consequences of IFN-beta for both the innate and adaptive arms of immunity. Despite no abnormalities in the proportional balance of CD4 and CD8 T cell populations in the peripheral blood, thymus, and spleen of IFN-beta-/- mice, activated lymph node and splenic T lymphocytes exhibit enhanced T cell proliferation and decreased tumor necrosis factor alpha production, relative to IFN-beta+/+ mice. Notably, constitutive and induced expression of tumor necrosis factor alpha is reduced in the spleen and bone marrow (BM) macrophages, respectively, of IFN-beta-/- mice. We also observe an altered splenic architecture in IFN-beta-/- mice and a reduction in resident macrophages. We identify a potential defect in B cell maturation in IFN-beta-/- mice, associated with a decrease in B220+ve/high/CD43-ve BM-derived cells and a reduction in BP-1, IgM, and CD23 expression. Circulating IgM-, Mac-1-, and Gr-1-positive cells are also substantially decreased in IFN-beta-/- mice. The decrease in the numbers of circulating macrophages and granulocytes likely reflects defective maturation of primitive BM hematopoiesis in mice, shown by the reduction of colony-forming units, granulocyte-macrophage. We proceeded to evaluate the in vivo growth of malignant cells in the IFN-beta-/- background and give evidence that Lewis lung carcinoma-specific tumor growth is more aggressive in IFN-beta-/- mice. Taken altogether, our data suggest that, in addition to the direct growth-inhibitory effects on tumor cells, IFN-beta is required during different stages of maturation in the development of the immune system.

Animals↗

PubMed2002

Interferon-alpha/beta-receptor interactions: a complex story unfolding.

The Type I interferons (IFN-alpha/beta) exhibit pleiotropic biological activities. Notably, the different IFN subtypes activate the same cell surface receptor complex to mediate variable responses. Accumulating evidence suggests that distinct differences in critical amino acid residues among the different IFN-alphas and IFN-beta determine the nature of the ligand-receptor interaction and the subsequent responses. This review focuses on IFN-receptor interactions, the key residues involved in this interaction and the potential for targeted modifications of the ligand to enhance bioactivity.

Animals↗