Epstein-Barr Virus  : EBV

The nasties Chronic Epstein-Barr Virus, Chronic Mononucleosis, re-occurring Glandular Fever and other names all a result of EBV, which in turn can lead to other nasties, ME/CFS, various cancers and more. I will be posting other studies involving this member of the Herpes family as time and health permits.
Till then read on.....
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By way of 'lite' reading here is a brief history of the Herpes family from Stanford U M
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Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr Virus


Suzanne D. Vernon(1,*), Toni Whistler(1), Barbara Cameron(2), Ian B. Hickie(3), William C. Reeves(1), Andrew Lloyd(2)

1 Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, Georgia 30333, United States
2 University of New South Wales, Sydney 2052, Australia
3 Brain and Mind Research Institute, University of Sydney, New South Wales, Sydney 2006, Australia

* Corresponding author
Email addresses:  SDV : svernon@cdc.gov;  TW : taw6@cdc.gov;  BC : b.cameron@unsw.edu.au;  IBH : anh@med.usyd.edu.au;  WCR : wcr1@cdc.gov;  AL : A.Lloyd@unsw.edu.au

Submission date 15 Jun 2005
Acceptance date 31 Jan 2006
Publication date 31 Jan 2006

Abstract

Background

Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV) infection.

Methods

We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC) samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides.

Results

Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene), DNAJB2 (DnaJ [Hsp40] homolog and CD99), CDK8 (cyclin-dependent kinase 8), E2F2 (E2F transcription factor 2), CDK8 (cyclin-dependent kinase 8), and ACTN2 (actinin, alpha 2), known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle.

Conclusions

These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis.

  Click Here for  the full study.....

Source: BMC Infectious Diseases   6:15
   Date January 31, 2006
   URL: < http://www.biomedcentral.com/1471-2334/6/15 >


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R. Glaser et al. / Brain, Behavior, and Immunity 19 (2005) 91­103

Stress-associated changes in the steady-state expression of latent Epstein-Barr virus: Implications for chronic fatigue syndrome and cancer

Ronald Glaser a,b,c, David A. Padgett a,b,c,d, Monica L. Litsky b, Robert A. Baiocchi c,e, Eric V. Yang a,b, Min Chen b, Peir-En Yeh b, Nancy G. Klimas f, Gailen D. Marshallg, Theresa Whiteside h,i, Ronald Herberman h, Janice Kiecolt-Glaser j, Marshall V. Williams a,c

Abstract

Antibodies to several Epstein-­Barr virus (EBV)-encoded enzymes are observed in patients with different EBV-associated diseases. The reason for these antibody patterns and the role these proteins might play in the pathophysiology of disease, separate from their role in virus replication, is unknown. In this series of studies, we found that purified EBV deoxyuridine triphosphate nucleotidohy-drolase (dUTPase) can inhibit the replication of human peripheral blood mononuclear cells in vitro and upregulate the production of TNF-α , IL-1β , IL-6, IL-8, and IL-10. It also enhanced the ability of natural killer cells to lyse target cells. The EBV dUTPase also significantly inhibited the replication of mitogen-stimulated lymphocytes and the synthesis of IFN-γ by cells isolated from lymph nodes and spleens obtained from mice inoculated with the protein. It also produced sickness behaviors known to be induced by some of the cytokines that were studied in the in vitro experiments. These symptoms include an increase in body temperature, a decrease in body mass and in physical activity. The data provide a new perspective on how an early nonstructural EBV-encoded protein can cause immune dysregulation and produce clinical symptoms observed in patients with chronic fatigue syndrome (CFS) separate from its role in virus replication and may serve as a new approach to help identify one of the etiological agents for CFS. The data also provide additional insight into the pathophysiology of EBV infection, inflammation, and cancer.

R. Glaser et al.   more .......

2004 Elsevier Inc. All rights reserved.
Keywords: EBV; Viral latency; Chronic fatigue syndrome; Cancer; dUTPase; Stress; Immune dysregulation
* Corresponding author. Fax: +1 614 292 1011.
E-mail address: glaser.1@osu.edu (R. Glaser).
0889-1591/$ - see front matter 2004 Elsevier Inc. All rights reserved.
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IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome.

Journal: In Vivo. 2004 Mar-Apr;18(2):101-6.

Authors: Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT.

Affiliation: Department of Medicine, William Beaumont Hospital and Wayne State University School of Medicine, Royal Oak, Michigan, USA.
mailto:lerner@cdimed.com

NLM Citation: PMID: 15113035

BACKGROUND:
A unique subset of patients with chronic fatigue syndrome (CFS) and IgM serum antibodies to cytomegalovirus (HCMV) non-structural gene products p52 and CM2 (UL 44 and UL 57) has been described.

PATIENTS AND METHODS:
Fifty-eight CFS patients and 68 non-CFS matched controls were studied. Serum antibodies to EBV viral capsid antigen (VCA) IgM and EBV Early Antigen, diffuse (EA, D) as well HVCMV(V), IgM and IgG; VP (sucrose, density purified V); p52 and CM2 IgM serum antibodies were assayed.

RESULTS:
Mean age of CFS patients was 44 years (75% women). Control patients were 9 years older (73% women). Serum EBV VCA IgM positive antibody titers were identified in 33 CFS patients (Group A subset EBV VCA IgM 62.3+/-8.3, neg. <20), but were not present in other CFS patients, (Group B subset EBV VCA IgM 6.8+/-0.7) controls (p<0.0001). EBV VCA IgM titers remained positive in CFS patients from Group A for 24-42 months.

CONCLUSION:
Serum antibody to EBV VCA IgM may be a specific diagnostic test for a second subset of CFS patients.

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Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr Virus

Suzanne D Vernon , Toni Whistler , Barbara Cameron , Ian B Hickie , William C Reeves and Andrew Lloyd
BMC Infectious Diseases 2006, 6:15
doi:10.1186/1471-2334-6-15
Published 31 January 2006

Abstract (provisional)

Background

Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV) infection.

Methods

We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC) samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides.

Results

Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene), DNAJB2 (DnaJ [Hsp40] homolog and CD99), CDK8 (cyclin-dependent kinase 8), E2F2 (E2F transcription factor 2), CDK8 (cyclin-dependent kinase 8), and ACTN2 (actinin, alpha 2), known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle.

Conclusions

These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis.

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Genetic Dissection of Cell Growth Arrest Functions Mediated by the Epstein-Barr Virus Lytic Gene Product, Zta

Antonio Rodriguez, Monica Armstrong, Daniel Dwyer, and Erik Flemington*

Harvard University and Dana-Farber Cancer Institute, Boston, Massachusetts 02115

Received 12 May 1999/Accepted 3 August 1999

Abstract

Expression of the Epstein-Barr virus (EBV) latency-associated genes activates cell cycle progression and drives immortalization of the infected cell. In contrast, progression of the EBV replication program occurs most efficiently in growth-arrested cells. Previous studies showed that the EBV-encoded immediate-early transcription factor, Zta, can induce expression of the cyclin-dependent kinase inhibitors, p21 and p27, the tumor suppressor, p53, and cell growth arrest. Moreover, Zta-mediated induction of growth arrest occurs independently of its transcriptional transactivation function. Here we show that substitution of Zta's basic DNA binding domain with the analogous region of the Zta homologue, c-Fos, abrogates Zta's ability to induce growth arrest and to induce p21, p27, or p53 expression, suggesting that protein-protein interactions between this region of Zta and key cell cycle control proteins are involved in signaling cell cycle arrest. We also show that despite the crucial role for Zta's basic domain in eliciting cell growth arrest, its amino terminus is required for efficient induction of p27 and it modulates the level of p53 induction. Last, we provide evidence that Zta-mediated inductions of p21, p27, and p53 occur, at least in part, through distinct pathways. Therefore, Zta interacts with multiple growth arrest pathways, a property which may have evolved partly as a means to ensure that lytic replication occurs in a growth-arrested setting in multiple different tissues in various states of differentiation.

* Corresponding author. Mailing address: Department of CIA, Rm. D1420B, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02446. Phone: (617) 632-3852. Fax: (617) 632-2662. E-mail: erik_flemington{at}dfci.harvard.edu

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Prolonged Illness after Infectious Mononucleosis Is Associated with Altered Immunity but Not with Increased Viral Load

Barbara Cameron, Mandvi Bharadwaj, Jacqueline Burrows, Chrysa Fazou, Denis Wakefield, Ian Hickie, Rosemary Ffrench, Rajiv Khanna, Andrew Lloyd, and Dubbo Infection Outcomes Study

Volume 193(2006), pages 664 - 671
DOI: 10.1086/500248

Abstract

Background. Primary Epstein-Barr virus (EBV) infection causes a spectrum of characteristics that range from asymptomatic seroconversion to severe infectious mononucleosis (IM), sometimes with prolonged symptoms and disability. We examined the relationships between clinical course, number of viral copies, and immunological parameters in a prospective cohort of subjects with recent IM.

Methods. Eight case patients with at least 6 months of disabling symptoms and 31 matched control subjects who had recovered promptly were included. Symptom scores were recorded at regular intervals over the course of 12 months. Cellular EBV load, EBV-specific antibody responses, lymphocyte subsets, and EBV-specific interferon (IFN) induction were measured.

Results. In case patients with prolonged illness, the severity of acute-phase symptoms was greater, the development of antiEBV nuclear antigen1 immunoglobulin G was more rapid, and the time to development of the peak IFN- response to the majority of latent-cycle EBV peptides was generally slower than those in control subjects. However, in both groups, neither viral nor immune parameters correlated with the severity or duration of symptoms.

Conclusions. The resolution of symptomatic IM is not determined by control of viremia, nor is it easily explained by altered host responses to EBV infection. The detailed determinants of delayed recovery remain to be elucidated.

J Infect Dis. 2006 Mar 1;193(5):664-71. Epub 2006 Jan 30
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