Critical Role of the Virus-Encoded MicroRNA-155 Ortholog in the Induction of Marek's Disease Lymphomas

Notwithstanding the well-characterised roles of a number of oncogenes in neoplastic transformation, microRNAs (miRNAs) are increasingly implicated in several human cancers. Discovery of miRNAs in several oncogenic herpesviruses such as KSHV has further highlighted the potential of virus-encoded miRNAs to contribute to their oncogenic capabilities. Nevertheless, despite the identification of several possible cancer-related genes as their targets, the direct in vivo role of virus-encoded miRNAs in neoplastic diseases such as those induced by KSHV is difficult to demonstrate in the absence of suitable models. However, excellent natural disease models of rapid-onset Marek's disease (MD) lymphomas in chickens allow examination of the oncogenic potential of virus-encoded miRNAs. Using viruses modified by reverse genetics of the infectious BAC clone of the oncogenic RB-1B strain of MDV, we show that the deletion of the six-miRNA cluster 1 from the viral genome abolished the oncogenicity of the virus. This loss of oncogenicity appeared to be primarily due to the single miRNA within the cluster, miR-M4, the ortholog of cellular miR-155, since its deletion or a 2-nucleotide mutation within its seed region was sufficient to inhibit the induction of lymphomas. The definitive role of this miR-155 ortholog in oncogenicity was further confirmed by the rescue of oncogenic phenotype by revertant viruses that expressed either the miR-M4 or the cellular homolog gga-miR-155. This is the first demonstration of the direct in vivo role of a virus-encoded miRNA in inducing tumors in a natural infection model. Furthermore, the use of viruses deleted in miRNAs as effective vaccines against virulent MDV challenge, enables the prospects of generating genetically defined attenuated vaccines

A Genome-Wide Comparative Evolutionary Analysis of Herpes Simplex Virus Type 1 and Varicella Zoster Virus

Herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are closely related viruses causing lifelong infections. They are typically associated with mucocutaneous or skin lesions, but may also cause severe neurological or ophthalmic diseases, possibly due to viral- and/or host-genetic factors. Although these viruses are well characterized, genome-wide evolutionary studies have hitherto only been presented for VZV. Here, we present a genome-wide study on HSV-1. We also compared the evolutionary characteristics of HSV-1 with those for VZV. We demonstrate that, in contrast to VZV for which only a few ancient recombination events have been suggested, all HSV-1 genomes contain mosaic patterns of segments with different evolutionary origins. Thus, recombination seems to occur extremely frequent for HSV-1. We conclude by proposing a timescale for HSV-1 evolution, and by discussing putative underlying mechanisms for why these otherwise biologically similar viruses have such striking evolutionary differences

Schmallenberg virus infection of ruminants: challenges and opportunities for veterinarians

François Claine, Damien Coupeau, Laetitia Wiggers, Benoît Muylkens, Nathalie Kirschvink Veterinary Department, Faculty of Sciences, Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), Namur, Belgium Abstract: In 2011, European ruminant flocks were infected by Schmallenberg virus (SBV) leading to transient disease in adult cattle but abortions and congenital deformities in calves, lambs, and goat kids. SBV belonging to the Simbu serogroup (family Bunyaviridae and genus Orthobunyavirus) was first discovered in the same region where bluetongue virus serotype 8 (BTV-8) emerged 5 years before. Both viruses are transmitted by biting midges (Culicoides spp.) and share several similarities. This paper describes the current knowledge of temporal and geographical spread, molecular virology, transmission and susceptible species, clinical signs, diagnosis, prevention and control, impact on ruminant health, and productivity of SBV infection in Europe, and compares SBV infection with BTV-8 infection in ruminants. Keywords: Schmallenberg virus, Europe, ruminants, revie

Schmallenberg virus among female lambs, Belgium, 2012

Reemergence of Schmallenberg virus (SBV) occurred among lambs (n = 50) in a sheep flock in Belgium between mid-July and mid-October 2012. Bimonthly assessment by quantitative reverse transcription PCR and seroneutralization demonstrated that 100% of lambs were infected. Viremia duration may be longer in naturally infected than in experimentally infected animals

In vivo and in vitro identification of a hypervariable region in Schmallenberg virus

Detected for the first time in 2011, Schmallenberg virus (SBV) is an orthobunyavirus of the Simbu serogroup that caused a large outbreak in European ruminants. In a tight time frame, data have been obtained on SBV epidemiology and the clinical pictures associated with this new viral infection, but little information is available on the molecular biology of SBV. In this study, SBV sequence variability was characterized from the central nervous system of two stillborn lambs in a naturally infected herd. A hypervariable region (HVR) was detected in the N-terminal region of the SBV Gc glycoprotein through sequencing and analysis of the two full-length genomes representative of intra-herd SBV dissemination. In vitro growth assays coupled with full-length genome sequencing were performed on the two isolates after successive cellular passages, showing an in vitro adaptation of SBV and mutation accumulation inside the HVR in the absence of immune selective pressure.</jats:p