MS is an immune mediated disease of the central nervous system (CNS) characterized by demyelination, axonal damage and neurologic disability. Although axonal injury occurs in MS, it is regarded as a secondary event to the myelin damage. This opinion has support both from epidemiological data and the findings of immunological abnormalities in spinal fluid that reflect an immune response to an as yet undetermined antigen, possibly a pathogen, in the cerebrospinal fluid. However, other parts of the DNA damage response are inactivated, demonstrating the finesse with which HSV-1 manipulates the DNA repair. Bibbs CJ Jr, Gajdusek DC. These proteins accumulate in the nucleus during lytic replication of the virus. The paper, published October 16 in PLOS ONE (Rumah et al., 2013), may be the first report of a human carrying the organism.
At day 14 post infection, mice were killed, and the brains, SCs and optic nerves collected, post-fixed and stained with the myelin stain, luxol fast blue (LFB). Although current disease-modifying therapeutic agents, IFN-β and copaxone, reduce relapses in a portion of relapsing-remitting MS patients, they are not curative, and their effectiveness in reducing disability progression in both relapsing-remitting and primary-progressive MS patients is unclear (2). These differences were also reflected in the ability of gD-1(delta290-299t) but not gD-1(306t) to block HSV type 1 infection of CHO-HVEM12 cells. Clinical features of MS include alterations in vision, sensory and motor disturbances and cognitive impairment. Gilles de la Tourette’s syndrome (TS), a tic disorder, is characterized by multiple motor and vocal tics, which wax and wane over time . Similarly, ICP0 mutants were analyzed for their association with RNF8. On examination, her blood pressure was 107/68 mm Hg, pulse was 108 bpm, respiratory rate was 18, and temperature was 99.6°F.
Analysis of other proteins from the TAP-MS experiments have identified and confirmed the interaction of two cancer-associated proteins with ICP0. We seek to determine whether these proteins may represent new degradation targets of ICP0, and if so, ICP0 may be useful in understanding the underlying functions of these proteins, both at the cellular level and in the context of HSV-1 infection. Lilley CE, Chaurushiya MS, Boutell C, Landry S, Suh J, Panier S, Everett RD, Stewart GS, Durocher D, and Weitzman MD. A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and the DNA damage responses. Biol., 1117, 593-616. (2010) 29:943-55. PMID: 20075863; PMC2837166.
Lilley CE, Chaurushiya MS, Boutell C, Everett RD, Weitzman MD. The intrinsic antiviral defense to incoming HSV-1 genomes includes specific DNA repair proteins and is counteracted by the viral protein ICP0. A recent large-scale genomewide association study identified alleles of the interleukin (IL)-2 receptor α gene (IL2RA, CD25), alleles of the IL-7 receptor α gene (IL7RA, CD127), both of which are genes related to the regulation of the immune response, and the human leukocyte antigen (HLA)-DR locus as heritable risk factors for MS (Hafler et al. (2011) 7:e1002084.  In addition, there is increased synthesis of Ig (elevated IgG index) suggesting an amplified production of Ig within the CNS compartment. Chaurushiya MS, Lilley CE, Aslanian A, Meisenhelder J, Scott DC, Landry S,Ticau S, Boutell C, Yates JR 3rd, Schulman BA, Hunter T, Weitzman MD. 1994;724:148–156.
and Silverstein, S.J. candidate in the labs of Vartanian and microbiologist Vincent Fischetti, Ph.D., at The Rockefeller University, took on the project for his Ph.D. To determine whether higher doses of HSV-IFN-γ were able to block HSV-IL-2-induced CNS demyelination, additional mice were subjected to the same experimental protocol, except that they were coinfected with 100-fold higher dose of HSV-IFN-γ (2 × 107 PFUs per eye) relative to HSV-IL-2 (2 × 105 PFUs per eye). Louis, Missouri, USA) were dissolved in 10% Tween-80 (Sigma-Aldrich) and PBS to a final concentration of 4 mg/ml or 1 mg/ml.