Archive for February 1st, 2013

Schmallenberg Virus Pathogenesis, Tropism and Interaction with the Innate Immune System of the Host

1 February, 2013

See on Scoop.itVirology News

Schmallenberg virus (SBV) was discovered in Germany (near the town of Schmallenberg) in November 2011 and since then has been found to be the cause of malformations and stillbirths in ruminants. SBV has spread very rapidly to many European countries including the Netherlands, Belgium, France and the United Kingdom. Very little is known about the biological properties of this virus and there is no vaccine available. In this study (i) we developed an approach (called reverse genetics) that allows the recovery of “synthetic” SBV under laboratory conditions; (ii) we developed a mouse model of infection for SBV; (iii) we showed that SBV replicates in neurons of experimentally infected mice similar to naturally infected lambs and calves; (iv) we developed viral mutants that are not as pathogenic as the original virus due to the inability to counteract the host cell defenses; and v) we identified mutations that are associated with increased virulence. This work provides the experimental tools to understand how this newly emerged virus causes disease in ruminants. In addition, it will now be possible to manipulate the SBV genome in order to develop highly effective vaccines.

 

Ed Rybicki‘s insight:

A timely paper on a serious new emerging virus of livestock.

See on www.plospathogens.org

PLOS Pathogens: The Importance of Prions

1 February, 2013

See on Scoop.itVirology News

While agent host-range and strain properties convinced early researchers of a viral etiology, the once unorthodox postulate that prion transmission occurs by conformational corruption of host-encoded cellular prion protein (PrPC) by a pathogenic isoform (PrPSc) is now widely accepted. Indeed, conformational templating is increasingly understood to be a general mechanism of protein-mediated information transfer and pathogenesis. The high infectivity of prions, their capacity to cause neurodegeneration in genetically tractable animal models, as well as the ability to culture prions in cells, or under cell-free conditions using defined components, provide finely controlled experimental settings in which to elucidate general mechanisms for all diseases involving protein conformational templating, and thus to develop integrated therapeutic approaches.

Ed Rybicki‘s insight:

These things have fascinated me since I heard and read about kuru and scrapie as a student – and they still do.  Alternative protein folding as a route to pathology – and transmissible!

 

Prion transmission graphic by Russell Kightely Media.

See on www.plospathogens.org

Dual Short Upstream Open Reading Frames Control Translation of a Herpesviral Polycistronic mRNA

1 February, 2013

See on Scoop.itVirology News

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of multicentric Castleman’s disease, primary effusion lymphoma and Kaposi’s sarcoma. KSHV expresses a number of transcripts with the potential to generate multiple proteins, yet relies on the cellular translation machinery that is primed to synthesize only one protein per mRNA. Here we report that the viral transcript encompassing ORF35–37 is able to direct synthesis of two proteins and that the translational switch is regulated by two short upstream open reading frames (uORFs) in the native 5′ untranslated region. uORFs are elements commonly found upstream of mammalian genes that function to interfere with unrestrained ribosomal scanning and thus repress translation of the major ORF. The sequence of the viral uORF appears unimportant, and instead functions to position the translation machinery in a location that favors translation of the downstream major ORF, via a reinitiation mechanism. Thus, KSHV uses a host strategy generally reserved to repress translation to instead allow for the expression of an internal gene.

 
See on www.plospathogens.org