The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Friday Science Review: August 19, 2011

Host-Cell Nucleolin, A Helping Hand for RSV

University of British Columbia ♦ University of Toronto ♦ Published in Nature Medicine, August 14th, 2011

Human respiratory syncytial virus (RSV), a Pneumovirus that is widely responsible for respiratory tract infections worldwide, appears to use host-cell nucleolin for viral entry. After making the discovery, researchers corroborated their finding with several experiments to show the importance that nucleolin plays in RSV infection. Neutralization experiments with nucleolin antibodies in vitro decreased RSV infection, while competition experiments with soluble nucleolin placed in cell culture medium also inhibited the virus from passing into cells. Interestingly, insect cells that are typically immune to the virus could be made susceptible through the transfection of human nucleolin. Mice given a prophylactic dose of RNAi, knocking down nucleolin in the lung, exhibited significant reduction in RSV infection. RSV interacts with host-cell nucleolin with a glycoprotein found in the viral envelope. There is currently no effective therapeutic or vaccination for the virus. Palivizumab (manufactured by MedImmune) is available for patients considered to be at high risk, but remains expensive.

Calpain-Mediated Degradation Spurs Autoimmune Disease

University of Toronto ♦ Samuel Lunenfeld Research Institute ♦ Toronto General Research Institute ♦ Princess Margaret Hospital ♦ Others..

Published in Nature Genetics, August 14th, 2011

The human Lyp protein tyrosine phosphatase (Lyp620W) plays a critical role in immune homeostasis by regulating T-cell antigen receptor signaling. A mutant of Lyp620W, Pep619W, is associated with increased risk of autoimmune disease. The mechanism by which this mutation promotes autoimmune disease is largely unknown. Recent findings suggest that degradation of Lyp protein is at the root of immune dysfunction. When analyzing Lyp transcripts in both wild-type mice and mice containing mutant alleles of the gene encoding Lyp620W, researchers found that transcript levels remained the same despite mutation. However, in the case of mice homozygous for the mutant allele, there was a drastic reduction in Pep619W protein. It appears that the enzyme calpain-1 degrades mutant versions of the protein, preventing Lyp protein from regulating the immune system. In the absence of functioning Lyp620W, lymphocyte and dendritic cell hyperresponsiveness ensues, leading to deleterious disease conditions.

Also see this review (written by U of T researchers and published in Trends in Biotechnology) on the use of biomaterials to create supportive micro-environments for the transplantation of neural stem/progenitor cells into the central nervous system..

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