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EBV, HHV-6, 7, 8, ETC.

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J Virol 2001 Dec;75(23):11641-50 Related Articles, Books, LinkOut

Gene expression profile of herpesvirus-infected T cells obtained using

immunomicroarrays: induction of proinflammatory mechanisms.

Mayne M, Cheadle C, Soldan SS, Cermelli C, Yamano Y, Akhyani N, Nagel JE,

Taub DD, Becker KG, son S.

Department of Pharmacology and Therapeutics, University of Manitoba,

Winnipeg, Manitoba, Canada. mmayne@...

Herpesvirus infections can frequently lead to acute inflammation, yet the

mechanisms regulating this event remain poorly understood. In order to

determine some of the immunological mechanisms regulated by human

herpesvirus infections, we studied the gene expression profile of

lymphocytes infected with human herpesvirus 6 (HHV-6) by using a novel

immunomicroarray. Our nylon-based immunomicroarray contained more than 1,150

immune response-related genes and was highly consistent between experiments.

Experimentally, we found that independently of the HHV-6 strain used to

infect T cells, multiple proinflammatory genes were increased and

anti-inflammatory genes were decreased at the mRNA and protein levels. HHV-6

strains A and B increased expression of the genes for interleukin-18

(IL-18), the IL-2 receptor, members of the tumor necrosis factor alpha

superfamily receptors, mitogen-activated protein kinase, and Janus kinase

signaling proteins. As reported previously, CD4 protein levels were also

increased significantly. Specific type 2 cytokines, including IL-10, its

receptor, and IL-14, were downregulated by HHV-6 infection and,

interestingly, amyloid precursor proteins and type 1 and 2 presenilins.

Thus, T cells respond to HHV-6 infection by inducing a type 1 immune

response that may play a significant role in the development and progression

of diseases associated with HHV-6, including pediatric, hematologic,

transplant, and neurologic disorders.

PMID: 11689646 [PubMed - indexed for MEDLINE]

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Am J Clin Pathol 2001 Nov;116(5):648-54 Related Articles, Books, LinkOut

Prevalence and cellular reservoir of latent human herpesvirus 6 in tonsillar

lymphoid tissue.

Roush KS, Domiati-Saad RK, Margraf LR, Krisher K, Scheuermann RH, BB,

Dawson DB.

Department of Pathology, University of Texas Southwestern Medical Center at

Dallas, USA.

There are few studies that examine prevalence, quantity, and cellular

proclivity of latent human herpesvirus 6 (HHV-6) in healthy populations. We

examined 69 tonsils with paired blood specimens from children without

evidence of acute infection. By polymerase chain reaction (PCR), HHV-6 was

detected at low levels in 100% of tonsils and 39% of blood samples (n = 27),

suggesting that prevalence of latent HHV-6 infection is high in children and

may be underestimated by PCR analysis of blood. Although HHV-6A and HHV-6B

were detected, HHV-6B predominated, being found in 97% of samples (n = 67).

Tonsil sections from 7 cases were examined by in situ hybridization using 2

HHV-6 probes and immunohistochemical analysis. Using both in situ

hybridization and immunohistochemical analysis, all tissues revealed marked

HHV-6-specific staining in the squamous epithelium of the tonsillar crypts

and rare positive lymphocytes. We conclude that HHV-6 is present universally

in tonsils of children, and tonsillar epithelium may be an important viral

reservoir in latent infection.

PMID: 11710680 [PubMed - indexed for MEDLINE]

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Blood 2001 Dec 15;98(13):3739-44 Related Articles, Books, LinkOut

Asymptomatic primary Epstein-Barr virus infection occurs in the absence of

blood T-cell repertoire perturbations despite high levels of systemic viral

load.

Silins SL, Sherritt MA, Silleri JM, Cross SM, Elliott SL, Bharadwaj M, Le

TT, on LE, Khanna R, Moss DJ, Suhrbier A, Misko IS.

Infectious Disease and Immunology Division, Queensland Institute of Medical

Research, Herston, Australia. sharons@...

Primary infection with the human herpesvirus, Epstein-Barr virus (EBV), may

result in subclinical seroconversion or may appear as infectious

mononucleosis (IM), a lymphoproliferative disease of variable severity. Why

primary infection manifests differently between patients is unknown, and,

given the difficulties in identifying donors undergoing silent

seroconversion, little information has been reported. However, a

longstanding assumption has been held that IM represents an exaggerated form

of the virologic and immunologic events of asymptomatic infection. T-cell

receptor (TCR) repertoires of a unique cohort of subclinically infected

patients undergoing silent infection were studied, and the results highlight

a fundamental difference between the 2 forms of infection. In contrast to

the massive T-cell expansions mobilized during the acute symptomatic phase

of IM, asymptomatic donors largely maintain homeostatic T-cell control and

peripheral blood repertoire diversity. This disparity cannot simply be

linked to severity or spread of the infection because high levels of EBV DNA

were found in the blood from both types of acute infection. The results

suggest that large expansions of T cells within the blood during IM may not

always be associated with the control of primary EBV infection and that they

may represent an overreaction that exacerbates disease.

PMID: 11739180 [PubMed - indexed for MEDLINE]

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Med Virol 2002 Mar;66(3):384-7 Related Articles, Books, LinkOut

Primary human herpesvirus-6 associated with an afebrile seizure in a

3-week-old infant.

Zerr DM, Yeung LC, Obrigewitch RM, Huang ML, Frenkel LM, Corey L.

Department of Pediatrics, University of Washington, Seattle, Washington.

We describe a 3-week-old male infant with an afebrile seizure in whom

serologic and polymerase chain reaction (PCR) findings support concomitant

primary human herpesvirus 6 (HHV-6) infection. Although HHV-6 infection has

been associated with first-time febrile seizures and encephalitis in both

immunocompetent and immunocompromised hosts, it has not been associated

previously with afebrile seizures in healthy infants. This report provides

additional evidence of the neuropathogenic potential of HHV-6. Copyright

2002 Wiley-Liss, Inc.

PMID: 11793391 [PubMed - in process]

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J Med Virol 2002 Apr;66(4):497-505 Related Articles, Books, LinkOut

Latent infection of human herpesvirus 6 in astrocytoma cell line and

alteration of cytokine synthesis.

Yoshikawa T, Asano Y, Akimoto S, Ozaki T, Iwasaki T, Kurata T, Goshima F,

Nishiyama Y.

Laboratory of Virology, Research Institute for Disease Mechanism and

Control, Nagoya University School of Medicine, Nagoya, Aichi, Japan.

In order to study the pathogenesis of HHV-6 infection in central nervous

system disorders, U251 cell line was infected with freshly isolated variant

B HHV-6. Although IEA/ex 3 antigen (immediate early protein) was detected in

infected cell nuclei, neither the presence of OHV-3 antigen (late antigen)

nor production of infectious virus was demonstrated. These results indicate

that abortive infection was established in the cells. After viral infection,

the viral genome copy in the infected cells gradually decreased and became

stable after 6 cell passages. At that point, HHV-6 gene expression was

restricted to only 2 immediate early genes (U90 and U94). However,

12-O-tetra-decanoyl (TPA) treatment induced transcription of other genes

(U31 and U39) by the 10th cell passage, indicating HHV-6 reactivation.

Moreover, production of two proinflamatory cytokines (IL-6 and IL-1[beta])

was up-regulated by the presence of the HHV-6 genome and TPA-induced

activation of the viral transcripts. Copyright 2002 Wiley-Liss, Inc.

PMID: 11857528 [PubMed - as supplied by publisher]

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Clin Infect Dis 2002 Feb 15;34(4):461-6 Related Articles, Books, LinkOut

Influenza Encephalopathy Associated with Infection with Human Herpesvirus 6

and/or Human Herpesvirus 7.

Sugaya N, Yoshikawa T, Miura M, Ishizuka T, Kawakami C, Asano Y.

Department of Pediatrics, Nippon Kokan Hospital, Kawasaki, Kanagawa

210-0852, Japan. sugaya-n@...

Influenza-associated encephalopathy is often reported in young Japanese

children, but its pathogenesis is unknown. Although influenza virus can be

demonstrated by throat culture for patients with encephalopathy, cultures of

samples of cerebrospinal fluids (CSF) do not yield the virus. Eight patients

with encephalopathy or complicated febrile convulsions had influenza virus

infection diagnosed by means of culture, polymerase chain reaction (PCR), or

rapid diagnosis using throat swabs. In all 8 cases, the results of PCR

testing of CSF specimens for influenza virus were negative. On the other

hand, human herpesvirus 6 (HHV-6) DNA was demonstrated in CSF specimens

obtained from 2 of 8 patients. In 3 of 8 patients, the presence of human

herpesvirus 7 (HHV-7) DNA was demonstrated in CSF specimens. Some cases of

influenza-associated encephalopathy reported in Japan may be attributable to

a dual infection with influenza virus and HHV-6, -7, or both. Another

possibility is that latent HHV-6 or HHV-7 in the brain is reactivated by

influenza, causing encephalopathy or febrile convulsions.

PMID: 11797172 [PubMed - in process]

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Nippon Rinsho 2001 Nov;59(11):2285-92 Related Articles, Books, LinkOut

[Hypersensitivity syndrome and HHV-6]

[Article in Japanese]

Tohyama M, Hashimoto K.

Department of Dermatology, Ehime University School of Medicice.

Hypersensitivity syndrome (HS) has been recognized as one of severe adverse

drug eruptions. HS has several characteristic features as follows. First,

the clinical symptoms are high fever, multiple lymphadenopathy, severe skin

rash, mononucleosis and multiple visceral involvement. Secondly, those

symptoms appear two to six weeks after the initiation of drug

administration. Thirdly, HS is induced by the specific drugs, carbamazepine,

phenytoin, salazosulfapyridine, allopurinol, diaphenylsulphone, and

mexiletine. Recently, we reported the association of HS with reactivation of

HHV-6, the causative virus for exanthem subitum. We propose the new disease

entity of HHV-6-associated drug eruption (HADE) because HS is composed of

two clinical phases, drug allergic reaction in the early phase and HHV-6

reactivation in the late phase.

Publication Types:

Review

Review, Tutorial

PMID: 11712420 [PubMed - indexed for MEDLINE]

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Scand J Infect Dis 2001;33(9):648-58 Related Articles, Books, LinkOut

Multiple sclerosis and Kaposi's sarcoma--chronic diseases associated with

new human herpesviruses?

Enbom M.

Department of Virology, Swedish Institute for Infectious Disease Control,

Solna.

Two diseases that for many years have been suspected to be of viral origin

are multiple sclerosis (MS) and Kaposi's sarcoma (KS). With the use of a new

technique called representational difference analysis both these diseases

have recently been associated with new lymphotropic herpesviruses, i.e.

human herpesviruses (HHV) 6 and 8. HHV-6 is a ubiquitous virus and the

etiological agent of exanthema subitum. Viral neuroinvasion occurs

frequently in primary HHV-6 infection, and meningitis, encephalitis and

demyelination have been described as rare complications. A relation with MS

has been suggested for HHV-6, as the virus has been detected in MS plaques

in the brain. Data from different studies are, however, conflicting and a

definitive role for HHV-6 in MS pathogenesis has not been established. HHV-8

is believed to be the causative agent of KS, and is also associated with

some rare hematological malignancies. The viral genome contains several

potential oncogenes that are believed to have been picked up from the human

genome during evolution. The role of HHV-8 in healthy, immunocompetent

individuals is however uncertain. In conclusion, the full spectrum of human

diseases associated with these new viruses is not yet understood, and rapid

developments in molecular biology will continue to shed new light on the

interactions between herpesviruses and their hosts.

Publication Types:

Review

Review, Tutorial

PMID: 11669221 [PubMed - indexed for MEDLINE]

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J Med Virol 2001 Nov;65(3):576-83 Related Articles, Books, LinkOut

Human herpesvirus 6 downregulates major histocompatibility complex class I

in dendritic cells.

Hirata Y, Kondo K, Yamanishi K.

Department of Microbiology, Osaka University Medical School, Yamada-oka,

Suita, Osaka 565-0871, Japan.

The expression of major histocompatibility complex (MHC) class I, class II,

CD1a, and CD 83 in dendritic cells (DCs) after infection with human

herpesvirus 6 (HHV-6) was examined. Whereas there was no significant change

in the expression of CD1a, CD83, and MHC class II in infected DCs, MHC class

I expression was downregulated after infection with HHV-6 variant A but not

HHV-6B. The expression of HHV-6 immediate-early or early genes was required

for the downregulation of MHC class I. The de novo synthesis of MHC class I

was greatly suppressed by infection with HHV-6A in DCs, while its rate of

degradation was only slightly elevated. These results suggest that HHV-6A

may escape from the host immune system in DCs by causing the downregulation

of MHC class I synthesis. Copyright 2001 Wiley-Liss, Inc.

PMID: 11596096 [PubMed - indexed for MEDLINE]

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Herpes 2001 Nov;8(3):64-8 Related Articles, Books

The association of herpes simplex virus and Alzheimer's disease: a potential

synthesis of genetic and environmental factors.

Pyles RB.

Department of Pediatrics and Sealy Center for Vaccine Development,

University of Texas Medical Branch, Galveston, TX, USA.

The chronic and sporadic nature of Alzheimer's disease (AD), in which the

majority of presenting cases are over 65 years of age, suggests that

compounded injury or long-term exposure to environmental factors is involved

in the aetiology, rather than inherited genetic alterations. Great hope has

been placed on identifying a causative infectious agent that would present

the potential for therapeutic or preventative vaccines or drugs. Although

not the sole causative agent, herpes simplex virus type 1 has been the most

clearly established pathogen to be associated with AD development to date.

Recent advances have begun to suggest mechanisms by which this ubiquitous,

neurotropic pathogen may predispose an individual to the development of AD.

Such progress should ultimately lead to therapeutic strategies that limit

predisposing neurological damage and potentially reverse the process,

increasing the quality and quantity of life in this patient population.

PMID: 11867022 [PubMed - in process]

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Arch Neurol 2001 Oct;58(10):1580-3 Related Articles, Books, LinkOut

Increase in peripheral CD4 bright+ CD8 dull+ T cells in Parkinson disease.

Hisanaga K, Asagi M, Itoyama Y, Iwasaki Y.

Department of Neurology, Miyagi National Hospital, 100 Kassenhara, Takase,

Yamamoto, Watari, Miyagi 989-2202, Japan.

BACKGROUND: Immune abnormalities are known to be involved in the

pathogenesis of sporadic Parkinson disease. OBJECTIVE: To examine whether

abnormalities in peripheral lymphocytes exist in Parkinson disease. METHODS:

Immune mediators, including CD1a, CD3, CD4, CD8, CD45RO, and Fas (CD95),

were examined in peripheral lymphocytes of patients by 3-color flow

cytometry. RESULTS: Patients with Parkinson disease displayed a

significantly greater population of circulating CD3+ CD4 bright+ CD8 dull+

lymphocytes than age-matched control subjects (P =.005) and patients with

cerebrovascular disease (P =.002). The increase in these cells appeared to

continue for at least 17 months. These T cells also expressed CD45RO and

Fas, markers for activated T cells, while CD1a, a marker for thymic T cells,

was negative, suggesting that these cells are mature T cells with immune

activities. CONCLUSIONS: As CD4+ CD8+ T cells are known to increase after

some specific viral infections, the continuous increase in CD4 bright+ CD8

dull+ T cells shown here may indicate postinfectious immune abnormalities

that are possibly associated with the pathogenesis of this slowly

progressive, multifactorial neurodegenerative disease.

PMID: 11594915 [PubMed - indexed for MEDLINE]

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Microb Pathog 2002 Feb;32(2):49-60 Related Articles, Books, LinkOut

Pathogenesis of transplacental virus infection: pestivirus replication in

the placenta and fetus following respiratory infection.

Swasdipan S, McGowan M, N, Bielefeldt-Ohmann H.

School of Veterinary Science, University of Queensland, Brisbane, North

Mymms, Qld 4072, Australia

Although transplacental virus infections account for considerable morbidity

and mortality in both animals and humans, very little is so far known about

the pathways whereby virus reaches the conceptus, the subsequent virus-host

interactions in the early phases of the infections, and the establishment of

persistent non-lethal infection. Using a natural animal model we recently

demonstrated that bovine pestivirus can spread from the site of infection to

the ovine fetus within 72 h, despite the expression of interferon in the

reproductive tract [1]. In the present study we demonstrate that pestivirus

first establishes infection and spread within the allantoic and amniotic

membranes and then the fetus, followed several days later by infection of

the uterine glands. However, virus replication and spread within the fetus

is, at least in part, controlled by fetal developmental factors. In fetuses

less than 25 days of gestational age, the virus remains restricted to the

bulbis cordis, the first brachial pouch and occasionally the aorta. Over the

next few days the virus spreads to multiple tissues, in addition to becoming

more widespread and pronounced within the initially infected tissues. A

potential role for the binucleated cells of the allantochorion in the spread

of the virus from the fetal to the maternal tissues was also found. These

cells expressed high levels of viral antigen just prior to and during the

time period in which virus antigen became detectable in the epithelial cells

of the uterine glands, in endothelial cells of uterine vessels and in

scattered macrophage-like cells in the uterine stroma. Most likely this

relatively late virus transfer is inconsequential for the mother, since it

occurs at a time when a maternal virus-specific antibody response is

becoming measurable. This is in contrast to the fetus, where the infection

will have established itself widely prior to the development of lymphoid

tissues and a functional immune response, thus setting the scenario for

development of specific tolerance to the persisting virus. Copyright 2002

Academic Press.

PMID: 11812211 [PubMed - in process]

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