Gammaherpesvirus Latency Accentuates EAE Pathogenesis: Relevance to Epstein-Barr Virus and Multiple Sclerosis

Epstein-Barr virus (EBV) has been identified as a putative environmental trigger of multiple sclerosis (MS), yet EBV's role in MS remains elusive. We utilized murine gamma herpesvirus 68 (γHV-68), the murine homolog to EBV, to examine how infection by a virus like EBV could enhance CNS autoimmunity. Mice latently infected with γHV-68 developed more severe EAE including heightened paralysis and mortality. Similar to MS, γHV-68EAE mice developed lesions composed of CD4 and CD8 T cells, macrophages and loss of myelin in the brain and spinal cord. Further, T cells from the CNS of γHV-68 EAE mice were primarily Th1, producing heightened levels of IFN-γ and T-bet accompanied by IL-17 suppression, whereas a Th17 response was observed in uninfected EAE mice. Clearly, γHV-68 latency polarizes the adaptive immune response, directs a heightened CNS pathology following EAE induction reminiscent of human MS and portrays a novel mechanism by which EBV likely influences MS and other autoimmune diseases

Limits on the high-energy gamma and neutrino fluxes from the SGR 1806-20 giant flare of December 27th, 2004 with the AMANDA-II detector

On December 27th 2004, a giant gamma flare from the Soft Gamma-ray Repeater 1806-20 saturated many satellite gamma-ray detectors. This event was by more than two orders of magnitude the brightest cosmic transient ever observed. If the gamma emission extends up to TeV energies with a hard power law energy spectrum, photo-produced muons could be observed in surface and underground arrays. Moreover, high-energy neutrinos could have been produced during the SGR giant flare if there were substantial baryonic outflow from the magnetar. These high-energy neutrinos would have also produced muons in an underground array. AMANDA-II was used to search for downgoing muons indicative of high-energy gammas and/or neutrinos. The data revealed no significant signal. The upper limit on the gamma flux at 90% CL is dN/dE < 0.05 (0.5) TeV^-1 m^-2 s^-1 for gamma=-1.47 (-2). Similarly, we set limits on the normalization constant of the high-energy neutrino emission of 0.4 (6.1) TeV^-1 m^-2 s^-1 for gamma=-1.47 (-2).Comment: 14 pages, 3 figure

First year performance of the IceCube neutrino telescope

The first sensors of the IceCube neutrino observatory were deployed at the South Pole during the austral summer of 2004-2005 and have been producing data since February 2005. One string of 60 sensors buried in the ice and a surface array of eight ice Cherenkov tanks took data until December 2005 when deployment of the next set of strings and tanks began. We have analyzed these data, demonstrating that the performance of the system meets or exceeds design requirements. Times are determined across the whole array to a relative precision of better than 3 ns, allowing reconstruction of muon tracks and light bursts in the ice, of air-showers in the surface array and of events seen in coincidence by surface and deep-ice detectors separated by up to 2.5 km

The ICECUBE prototype string in AMANDA

The Antarctic Muon And Neutrino Detector Array (Amanda) is a high-energy neutrino telescope. It is a lattice of optical modules (OM) installed in the clear ice below the South Pole Station. Each OM contains a photomultiplier tube (PMT) that detects photons of Cherenkov light generated in the ice by muons and electrons. IceCube is a cubic-kilometer-sized expansion of Amanda currently being built at the South Pole. In IceCube the PMT signals are digitized already in the optical modules and transmitted to the surface. A prototype string of 41 OMs equipped with this new all-digital technology was deployed in the Amanda array in the year 2000. In this paper we describe the technology and demonstrate that this string serves as a proof of concept for the IceCube array. Our investigations show that the OM timing accuracy is 5 ns. Atmospheric muons are detected in excellent agreement with expectations with respect to both angular distribution and absolute rate

Limits to the muon flux from neutralino annihilations in the Sun with the AMANDA detector

A search for an excess of muon-neutrinos from neutralino annihilations in the Sun has been performed with the AMANDA-II neutrino detector using data collected in 143.7 days of live-time in 2001. No excess over the expected atmospheric neutrino background has been observed. An upper limit at 90% confidence level has been obtained on the annihilation rate of captured neutralinos in the Sun, as well as the corresponding muon flux limit at the Earth, both as functions of the neutralino mass in the range 100 GeV-5000 GeV.Comment: 13 pages, 3 figures. Submitted to Astropart. Phy

An Updated Meta-Analysis of Risk of Multiple Sclerosis following Infectious Mononucleosis

Background: Multiple sclerosis (MS) appears to develop in genetically susceptible individuals as a result of environmental exposures. Epstein-Barr virus (EBV) infection is an almost universal finding among individuals with MS. Symptomatic EBV infection as manifested by infectious mononucleosis (IM) has been shown in a previous meta-analysis to be associated with the risk of MS, however a number of much larger studies have since been published.Methods/Principal Findings: We performed a Medline search to identify articles published since the original meta-analysis investigating MS risk following IM. A total of 18 articles were included in this study, including 19390 MS patients and 16007 controls. We calculated the relative risk of MS following IM using a generic inverse variance with random effects model. This showed that the risk of MS was strongly associated with IM (relative risk (RR) 2.17; 95% confidence interval 1.97-2.39; p<10(-54)).Discussion: Our results establish firmly that a history of infectious mononucleosis significantly increases the risk of multiple sclerosis. Future work should focus on the mechanism of this association and interaction with other risk factors