Human herpesvirus 6

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1-Bilateral optic neuropathy and unilateral tonic pupil associated with

acute human herpesvirus 6 infection: a case report.

2-Co-localization of human herpes virus 6 and tissue plasminogen activator

in multiple sclerosis brain tissue.

3-Viral replication-independent blockade of dendritic cell maturation and

interleukin-12 production by human herpesvirus 6.

4-High prevalence of viral genomes and multiple viral infections in the

myocardium of adults with " idiopathic " left ventricular dysfunction.

5-Etiology of mumps-like illnesses in children and adolescents vaccinated

for measles, mumps, and rubella.

6-Early and late HHV-6 gene transcripts in multiple sclerosis lesions and

normal appearing white matter.

7-Human herpesvirus 6B induces cell cycle arrest concomitant with p53

phosphorylation and accumulation in T cells.

8-Detection of herpesvirus-6A in a case of subacute cerebellitis and

myoclonic dystonia.

9-The laboratory confirmation of suspected measles cases in settings of low

measles transmission: conclusions from the experience in the Americas.

10-Transient decrease in cerebral white matter diffusivity on MR imaging in

human herpes virus-6 encephalopathy.

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Graefes Arch Clin Exp Ophthalmol. 2005 Feb;243(2):175-7. Epub 2004 Sep 10.

Related Articles, Links

Bilateral optic neuropathy and unilateral tonic pupil associated with acute

human herpesvirus 6 infection: a case report.

Oberacher-Velten IM, Jonas JB, Junemann A, Schmidt B.

Department of Ophthalmology and University Eye Hospital, University of

Erlangen-Nurnberg, Schwabachanlage 6, 91054, Erlangen, Germany.

isabelvelten@...

BACKGROUND: Human herpesvirus 6 (HHV-6), a widespread virus and causative

agent of exanthema subitum in children, has been associated with a number of

neurologic disorders including cranial nerve palsies, seizures,

encephalitis, meningitis, and multiple sclerosis. PATIENT: A 31-year-old man

presented with bilateral optic neuropathy, disc edema, and unilateral tonic

pupil, which were found to be associated with acute HHV-6 infection. The

patient had been suffering from juvenile diabetes for 5 years. One week

after onset of intravenous antiviral therapy with foscarnet, disc edema

subsided, and tonic pupil reaction was no longer detectable.

CONCLUSIONS: HHV-6 infection may play a role as a causative agent in

patients with optic neuropathy and tonic pupil.

PMID: 15742213 [PubMed - in process]

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Med Sci Monit. 2005 Feb 25;11(3):BR84-87 [Epub ahead of print] Related

Articles, Links

Co-localization of human herpes virus 6 and tissue plasminogen activator in

multiple sclerosis brain tissue.

Virtanen JO, Zabriskie JB, Siren V, Friedman JE, Lyons MJ, Edgar M, Vaheri

A, Koskiniemi M.

Haartman Institute, Department of Virology, University of Helsinki, Finland.

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the

central nervous system of unknown etiology. Several viruses have been

suggested as playing a role in the pathogenesis of MS. The aim of this study

was to investigate the interrelationship of human herpesvirus 6 (HHV-6) and

plasminogen activation at the cellular level in MS plaques.

Material/Methods: Brain tissue specimens obtained from autopsies of 15

patients with MS and 10 controls were studied immunohistochemically for

HHV-6 and cytomegalovirus (CMV) antigen and tissue plasminogen activator

(tPA) protein. The presence of Ebstein-Barr virus (EBV) EBER RNA was studied

using RNA in situ hybridization. Results: HHV-6 antigen was identified in

the cells of 67% (10/15) of MS brain sections and 30% (3/10) of the control

sections. All samples were negative for CMV antigen and all samples with

intact RNA were negative for EBV EBER RNA as demonstrated by in situ

hybridization. tPA expression was found to be increased in MS plaques

compared with the control samples. Interestingly, in 5 MS samples both HHV-6

antigen and tPA stained clearly, compared with none in the controls, but

HHV-6 and tPA only occasionally co-localized in the same cells.

Conclusions: At the cellular level, HHV-6 and plasminogen activation seem to

co-localize in MS.

PMID: 15735559 [PubMed - as supplied by publisher]

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J Virol. 2005 Mar;79(5):2807-13. Related Articles, Links

Viral replication-independent blockade of dendritic cell maturation and

interleukin-12 production by human herpesvirus 6.

AP, Paolucci C, Di Lullo G, Burastero SE, Santoro F, Lusso P.

Unit of Human Virology, Department of Biological and Technological Research

(DIBIT), San Raffaele Scientific Institute, Via Olgettina no. 58, 20132

Milan, Italy.

Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive

CD4(+)-T-lymphotropic betaherpesvirus that causes severe human thymocyte

depletion in heterochimeric SCID-hu thy/liv mice and has been implicated as

a potential cofactor in the progression of AIDS. However, the mechanisms of

HHV-6-mediated immunosuppression have not yet been fully elucidated. We

investigated the phenotypic and functional alterations induced by HHV-6 on

peripheral blood-derived human dendritic cells (DC). The infection of DC

with HHV-6 A or B was nonproductive, as revealed by calibrated real-time PCR

measuring the accumulation of viral genome equivalents over time.

Nevertheless, preexposure to HHV-6 markedly impaired the maturation of DC

driven by gamma interferon and lipopolysaccharide, as shown by the reduced

surface expression of major histocompatibility complex class I molecules,

HLA-DR, CD40, and CD80. Moreover, HHV-6, but not the closely related

betaherpesvirus HHV-7, dramatically suppressed the secretion of

interleukin-12 (IL-12) p70 by DC, while the production of other cytokines

that influence DC maturation, i.e., IL-10 and tumor necrosis factor alpha,

was not significantly modified. Likewise, the secretion of the CC chemokines

macrophage inflammatory protein 1beta and RANTES was unaltered.

Functionally, a pretreatment with HHV-6 impaired the ability of DC to

stimulate allogeneic T-cell proliferation.

Altogether, these data identify interference with the functional maturation

of DC as a potential mechanism of HHV-6-mediated immunosuppression.

PMID: 15708999 [PubMed - in process]

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Circulation. 2005 Feb 22;111(7):887-93. Epub 2005 Feb 7. Related Articles,

Links

High prevalence of viral genomes and multiple viral infections in the

myocardium of adults with " idiopathic " left ventricular dysfunction.

Kuhl U, Pauschinger M, Noutsias M, Seeberg B, Bock T, Lassner D, Poller W,

Kandolf R, Schultheiss HP.

Charite-University Medicine Berlin, Campus lin, Department of

Cardiology and Pneumology, Hindenburgdamm 30, 12200 Berlin, Germany.

uwe.kuehl@...

BACKGROUND: For a long time, enteroviruses have been considered to be the

most common cause of acute viral myocarditis (MC), with possible transition

from MC to dilated cardiomyopathy (DCM). Recent investigations have shown,

however, that other viruses are also frequently encountered in MC patients,

suggesting that persistence of various virus species may play a pathogenic

role in the transition from MC to DCM. The purpose of this study was to

screen endomyocardial biopsies (EMBs) from patients with " idiopathic " DCM

for the presence of viral genomes by using polymerase chain reaction (PCR)

to assess the frequency of cardiac viral infections that may be involved in

the pathogenesis of the disease. METHODS AND RESULTS: EMBs were obtained for

PCR analysis from 245 consecutive patients (median left ventricular ejection

fraction, 35.0%; range, 9% to 59%). PCR and reverse transcription-PCR were

performed to detect the genomic sequences of enterovirus (EV), adenovirus

(ADV), human cytomegalovirus (HCMV), herpes simplex virus, Epstein-Barr

virus (EBV), human herpesvirus 6 (HHV-6), parvovirus B19 (PVB19), and

influenza A and B viruses. Myocardial inflammation was assessed by

histological and immunohistological analyses. Viral genomes could be

amplified from EMBs of 165 (67.4%) of the 245 DCM patients: EV=23 (9.4%),

ADV=4 (1.6%), PVB19=126 (51.4%), HHV-6=53 (21.6%), EBV=5 (2.0%), HCMV=2

(0.8%), including n=45 cases (27.3%) with multiple infections. Active or

borderline myocarditis according to the Dallas classification did not exist

in any case. Lymphocyte and macrophage infiltrates were not significantly

different in virus-positive versus virus-negative patients.

CONCLUSIONS: Viral genomes were frequently detected in EMBs of patients with

systolic left ventricular dysfunction. Our data suggest that myocardial

persistence of various viruses, often presenting as multiple infections, may

play a role in the pathogenesis of DCM far more frequently than suspected so

far.

PMID: 15699250 [PubMed - in process]

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J Infect Dis. 2005 Mar 1;191(5):719-23. Epub 2005 Jan 19. Related Articles,

Links

Etiology of mumps-like illnesses in children and adolescents vaccinated for

measles, mumps, and rubella.

kin I, Jokinen S, Paananen A, Leinikki P, Peltola H.

National Public Health Institute, Helsinki, Finland. irja.davidkin@...

The possible viral etiology of mumps-like illnesses in patients vaccinated

for measles, mumps, and rubella (MMR) was studied by use of serum samples

prospectively collected, during 1983-1998, from 601 acutely ill Finnish

children and adolescents with mumps-like symptoms. Mumps virus was excluded

by testing serum samples for mumps antibodies, and the serum samples were

further tested for antibodies to adenovirus, enterovirus, Epstein-Barr

virus, parainfluenza virus types 1-3, and parvovirus B19. The serum samples

of 114 children <4 years old were also tested for antibodies to human

herpesvirus 6 (HHV-6). A viral etiology was verified in 84 cases (14%), most

commonly Epstein-Barr virus (7%), followed by parainfluenza virus types 1,

2, or 3 (4%) and adenovirus (3%). HHV-6 infection was found in 5 children <4

years old (4%).

This study confirms that mumps-like symptoms in MMR-vaccinated children and

adolescents are often not caused by mumps virus infection. Careful

laboratory-based diagnostic testing of MMR-vaccinated children and

adolescents who develop clinical symptoms compatible with those of mumps is

important in the treatment of individual patients, in the comprehension of

the true epidemiology of these illnesses, and in the evaluation of the

impact of MMR vaccination programs.

PMID: 15688285 [PubMed - indexed for MEDLINE]

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Brain. 2005 Mar;128(Pt 3):516-27. Epub 2005 Jan 19. Related Articles, Links

Early and late HHV-6 gene transcripts in multiple sclerosis lesions and

normal appearing white matter.

Opsahl ML, Kennedy PG.

University of Glasgow Department of Neurology, Division of Clinical

Neurosciences, Institute of Neurological Sciences, Southern General

Hospital, Glasgow, UK.

Multiple sclerosis is an inflammatory demyelinating disease of the CNS, the

aetiology of which is believed to have both genetic and environmental

components. We have investigated one of the candidate viruses for the

environmental component of multiple sclerosis, the neurotropic human

herpesvirus 6 (HHV-6). Utilizing fluorescent in situ hybridization (FISH)

techniques, we have examined human post-mortem tissues for the presence of

immediate early and late viral gene expression in multiple sclerosis patient

normal appearing white matter (NAWM), lesional tissue and normal control

brain samples. HHV-6 gene transcription was detected in all tissue samples

and was restricted to oligodendrocytes, as determined by double mRNA FISH

analysis. Quantitative analysis of viral mRNA expression indicated that both

NAWM and lesional multiple sclerosis samples exhibited significantly higher

levels of HHV-6 expression compared with the normal control samples.

Lesional samples exhibited the highest levels of viral gene expression, with

NAWM exhibiting an intermediate level between lesional and control tissues.

Immunofluorescence against early and late HHV-6 proteins verified active

translation of HHV-6 viral mRNA in oligodendrocytes. Southern blot analysis

of nested polymerase chain reactions using extracted genomic DNA and cDNA

confirmed the presence of the HHV-6 genome in all individuals, with the

active expression profile mirroring the FISH results.

The frequent high level of HHV-6 infection in multiple sclerosis samples

suggests a possible role in pathogenesis.

PMID: 15659422 [PubMed - indexed for MEDLINE]

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J Virol. 2005 Feb;79(3):1961-5. Related Articles, Links

Human herpesvirus 6B induces cell cycle arrest concomitant with p53

phosphorylation and accumulation in T cells.

Oster B, Bundgaard B, Hollsberg P.

Department of Medical Microbiology and Immunology, Bartholin Building,

University of Aarhus, DK-8000 Aarhus C, Denmark.

We studied the interactions between human herpesvirus 6B (HHV-6B) and its

host cell. Productive infections of T-cell lines led to G1/S- and G2/M-phase

arrest in the cell cycle concomitant with an increased level and enhanced

DNA-binding activity of p53. More than 70% of HHV-6B-infected cells did not

bind annexin V, indicating that the majority of cells were not undergoing

apoptosis. HHV-6B infection induced Ser20 and Ser15 phosphorylation on p53,

and the latter was inhibited by caffeine, an ataxia telangiectasia mutated

kinase inhibitor.

Thus, a productive HHV-6B infection suppresses T-cell proliferation

concomitant with the phosphorylation and accumulation of p53.

PMID: 15650224 [PubMed - indexed for MEDLINE]

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J Med Virol. 2005 Mar;75(3):427-9. Related Articles, Links

Detection of herpesvirus-6A in a case of subacute cerebellitis and myoclonic

dystonia.

Borghi E, Pagani E, Mancuso R, Delbue S, Valli M, Mazziotti R, Giordano L,

Micheli R, Ferrante P.

Department of Biomedical Science and Technology, University of Milan, Milan,

Italy.

This is a case study of a child who developed roseola infantum first, then

varicella, and was later affected by acute cerebellar syndrome, severe

truncal ataxia, and myoclonic dystonia. Human herpesvirus 6 (HHV-6) A and B

were detected in the cerebrospinal fluid (CSF) and peripheral blood,

respectively, upon ataxia onset.

The intricacy of this case suggests multifaceted conclusions ranging from

the need for a multidirectional approach to neurological diseases, to

confirmation of a more pronounced neurotropism of HHV-6A and a possible role

of viruses in myoclonic dystonia syndrome, although this last hypothesis

should be confirmed by larger studies. 2005 Wiley-Liss, Inc.

PMID: 15648060 [PubMed - in process]

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Bull World Health Organ. 2004 Nov;82(11):852-7. Epub 2004 Dec 14. Related

Articles, Links

The laboratory confirmation of suspected measles cases in settings of low

measles transmission: conclusions from the experience in the Americas.

Dietz V, Rota J, Izurieta H, Carrasco P, Bellini W.

Immunization Unit, Family and Community Health Unit, Pan American Health

Organization, Washington DC, USA. vxd0@...

The Americas have set a goal of interrupting indigenous transmission of

measles using a strategy developed by the Pan American Health Organization

(PAHO). This strategy includes recommendations for vaccination activities to

achieve and sustain high immunity in the population and is complemented by

sensitive epidemiological surveillance systems developed to monitor

illnesses characterized by febrile rash, and to provide effective

virological and serological surveillance. A key component in ensuring the

success of the programme has been a laboratory network comprising 22

national laboratories including reference centres. Commercially available

indirect enzyme immunoassay kits (EIA) for immunoglobulin M (IgM)-class

antibodies are currently being used throughout the region. However, because

there are few or no true measles cases in the region, the positive

predictive value of these diagnostic tests has decreased.

False-positive results of IgM tests can also occur as a result of testing

suspected measles cases with exanthemata caused by Parvovirus B19, rubella

and Human herpesvirus 6, among others. In addition, as countries maintain

high levels of vaccination activity and increased surveillance of rash and

fever, the notification of febrile rash illness in recently vaccinated

people can be anticipated.

Thus, managers in the measles elimination programme must be prepared to

address the interpretation of a positive result of a laboratory test for

measles IgM when clinical and epidemiological data may indicate that the

case is not measles. The interpretation of an IgM-positive test under

different circumstances and the definition of a vaccine-related rash illness

in a setting of greatly reduced, or absent, transmission of measles is

discussed.

PMID: 15640921 [PubMed - indexed for MEDLINE]

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Brain Dev. 2005 Jan;27(1):30-3. Related Articles, Links

Transient decrease in cerebral white matter diffusivity on MR imaging in

human herpes virus-6 encephalopathy.

Akasaka M, Sasaki M, Ehara S, Kamei A, Chida S.

Department of Pediatrics, Iwate Medical University, 19-1 Uchimaru, Morioka,

Iwate 020-8505, Japan. manami-imed@...

We report a 16-month-old boy with human herpes virus-6 (HHV-6)

encephalopathy showing transient abnormalities of the cerebral white matter

on magnetic resonance imaging. Diffusion-weighted imaging (DWI) demonstrated

diffuse high signal intensity in the bilateral cerebral white matter areas.

The signal changes on DWI subsequently resolved, and cerebral atrophy

resulted. The transient decrease in the cerebral white matter diffusivity

seen in the present case may reflect axonal involvement secondary to the

glial or neuronal damage in HHV-6 encephalopathy.

PMID: 15626538 [PubMed - in process]

Muta T, Kamo M, Gondo H, Kato K, Eto T, Shibuya T, Fukuda T, Miyamoto T,

Nagafuji K, Ichinohe T, Harada M. Related Articles, Links

Human herpesvirus-6 encephalitis followed by severe acute GVHD after a stem

cell transplant from a microchimeric non-inherited maternal antigen

(NIMA)-mismatched sibling.

Bone Marrow Transplant. 2005 Feb;35(4):411-3. No abstract available.

PMID: 15608657 [PubMed - in process]