Shingles Research Today is a free monthly online journal that collates and summarizes the latest research about Shingles, including details on symptoms, treatment, causes, virus.

Transcriptional coactivator HCF-1 couples the histone chaperone Asf1b to HSV-1 DNA replication components.

Peng H, Nogueira ML, Vogel JL, Kristie TM

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bld 4-131, 4 Center Drive, Bethesda, MD 20892.

The cellular transcriptional coactivator HCF-1 interacts with numerous transcription factors as well as other coactivators and is a component of multiple chromatin modulation complexes. The protein is essential for the expression of the immediate early genes of both herpes simplex virus (HSV) and varicella zoster virus and functions, in part, by coupling chromatin modification components including the Set1 or MLL1 histone methyltransferases and the histone demethylase LSD1 to promote the installation of positive chromatin marks and the activation of viral immediately early gene transcription. Although studies have investigated the role of HCF-1 in both cellular and viral transcription, little is known about other processes that the protein may be involved in. Here we demonstrate that HCF-1 localizes to sites of HSV replication late in infection. HCF-1 interacts directly and simultaneously with both HSV DNA replication proteins and the cellular histone chaperone Asf1b, a protein that regulates the progression of cellular DNA replication forks via chromatin reorganization. Asf1b localizes with HCF-1 in viral replication foci and depletion of Asf1b results in significantly reduced viral DNA accumulation. The results support a model in which the transcriptional coactivator HCF-1 is a component of the HSV DNA replication assembly and promotes viral DNA replication by coupling Asf1b to DNA replication components. This coupling provides a novel function for HCF-1 and insights into the mechanisms of modulating chromatin during DNA replication.

Published 5 February 2010 in Proc Natl Acad Sci U S A.
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Articles on Shingles published 4 February 2010:

Divergence and genotyping of human alpha-herpesviruses: An overview.   Infect Genet Evol, 10(1): 14-25.

Herpesviruses are large DNA viruses that are highly disseminated among animals. Of the eight herpesviruses identified in humans, three are classified into the alpha-herpesvirus subfamily: herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), which are typically associated with mucocutaneous lesions, and varicella-zoster virus (VZV), which is the cause of chicken pox and herpes zoster. All three viruses establish lifelong infections and may also induce more severe symptoms, such as neurological ... [Abstract] [Full-text]

A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis.   N Engl J Med, 362(5): 416-426.

BACKGROUND: Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis. METHODS: We randomly assigned 1326 patients in an approximate 1:1:1 ratio to receive one of two cumulative doses of cladribine tablets (either 3.5 mg or 5.25 mg per kilogram of body weight) or matching placebo, given in two or four short courses for the ... [Abstract] [Full-text]

Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis.   N Engl J Med, 362(5): 402-415.

BACKGROUND: Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis. METHODS: In this 12-month, double-blind, double-dummy study, we randomly assigned 1292 patients with relapsing-remitting multiple sclerosis who had a recent history of at least one relapse to receive either oral fingolimod at a daily dose of either 1.25 or ... [Abstract] [Full-text]

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Varicella zoster virus (VZV) causes varicella and herpes zoster, diseases characterized by distinct cutaneous rashes. DC are essential for inducing anti-viral immune responses, however the contribution of DC subsets to the immune control during natural cutaneous VZV infection has not been investigated. Immunostaining showed that compared to normal skin, the proportion of cells expressing DC-SIGN (dermal DC marker) or DC-LAMP and CD83 (mature DC markers) were not significantly altered in ... [Abstract] [Full-text]

A case of reversible restless legs syndrome (RLS) and sleep-related eating disorder relapse triggered by acute right leg herpes zoster infection: Literature review of spinal cord and peripheral nervous system contributions to RLS.   Sleep Med.

Restless legs syndrome (RLS) is thought to be due to abnormalities of iron metabolism in the central nervous system; however, occasional cases are associated with lesions of the spinal cord, spinal rootlets, and peripheral nervous system. This is a case report of RLS exacerbated by shingles with a review of the literature of extra-cerebral lesions or disorders causing or contributing to RLS. [Abstract] [Full-text]

Articles on Shingles published 3 February 2010:

Intrathecal antibody production against Epstein-Barr and other neurotropic viruses in pediatric and adult onset multiple sclerosis.   J Neurol, 257(2): 212-6.

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The aim of this study was to describe the demographic, clinical and laboratory features of idiopathic acute transverse myelitis (IATM). Patients with non-compressive ATM receiving care at Hospital da Lagoa, Rio de Janeiro (Brazil) between 2000 and 2008 were selected. Of the 70 cases of acute myelopathies, the idiopathic form was identified in 41 following exclusion of the cases associated with systemic lupus erythematosus (n = 1), Sjogren's syndrome (n = 1), herpes zoster (n = 1), ... [Abstract] [Full-text]

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OBJECTIVES: Human herpesviruses, e.g., herpes simplex virus (HSV) type 1, Epstein-Barr virus, and cytomegalovirus, appear in saliva at greater frequency in persons infected with human immunodeficiency virus (HIV) than in healthy individuals. However, it is not known if varicella zoster virus (VZV) and HSV-2 appear simultaneously during HIV infection at greater frequency in saliva in this era of highly active antiretroviral therapy (HAART). The aim of this study was to investigate the prevalence ... [Abstract] [Full-text]

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