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Human Herpesvirus 6 Infection in Normal Human Brain Tissue
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Mario Luppi, Patrizia Barozzi, Antonio Maiorana, Roberto Marasca, Giuseppe Torelli; Human Herpesvirus 6 Infection in Normal Human Brain Tissue, The Journal of I
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HHV-6 causes a primary infection usually during the first two-three years of life, after which it becomes dormant predominantly inside monocytes and macrophages.
“Similar to all herpesviruses, HHV-6 causes a primary infection, usually during the first two-three years of life, after which it becomes dormant predominantly inside monocytes and macrophages [3,4,5].”
From Human Herpesvirus 6—A Rare Aetiologic Agent for CNS Infections in Immunocompetent Individuals or an Underestimation? (2024) · cites this paper as [3]
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“It includes brain tissue (60, 110, 248), liver tissue (155, 186,”
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“Consistent with this hypothesis, HHV-6-specific DNA was detected by PCR in over 80% of autopsy brain specimens, suggesting that the CNS of most people is persistently infected with HHV-6 (87, 329, 330).”
Soldan, S. S., Berti, R., Salem, N., Secchiero, P., Flamand, L., Calabresi, P. A., Brennan, M. B., Maloni, H. W., McFarland, H. F., Lin, H. C., et al. (1997) · Nature Medicine · doi:10.1038/nm1297-1394 · Cited by 445
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Self-citationLaboratory and Clinical Aspects of Human Herpesvirus 6 Infections
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Cross‐reactivity with myelin basic protein and human herpesvirus‐6 in multiple sclerosis
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“Human herpesvirus 6 can also be detected in the brains of healthy elderly patients, and in multiple sclerosis patients [28,47].”
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“Both variant viruses were detected in the brain of patients who died of causes related or unrelated to HHV-6, which demonstrates that both variant viruses can invade and be harbored in the brain (61,78-82).”
BackgroundHuman Herpesvirus 6 Is Associated with Focal Encephalitis
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“Recent attention has also focused on the roles of HHV-6 in causing neurological disease (23, 33).”
BackgroundIto, M., Blumberg, B. M., Mock, D. J., Goodman, A. D., Moser, A. B., Moser, H. W., Smith, K. D., & Powers, J. M. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.10.1004 · Cited by 125
“Luppi et al detected HHV6-DNA in 11 of 13 normal brain tissue specimens without neurological symptoms (28), and the CNS is also considered to be a site of latent infection for HHV6 (29).”
BackgroundNeuroimaging of herpesvirus infections in children
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“The virus remains latent throughout the body, including the salivary glands, white blood cells, and the brain [103, 106–108].”
BackgroundProgress with retroviral gene vectors
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Detection of Human Herpesvirus 6 by Reverse Transcription-PCR
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“The last example poses the question whether a destructive process in the CNS might lead to release of latent HHV-6 DNA from the brain (48) into the CSF.”
BackgroundHuman herpes virus 6 and multiple sclerosis
Moore, F. G. A., & Wolfson, C. M. (2002) · Acta Neurologica Scandinavica · doi:10.1034/j.1600-0404.2002.01251.x · Cited by 83
“1999 (35) Hungary ELISA Compared titres Number and sex: 3 F/ 4 M Mean age: 36 (25-53) Diagnostic criteria: (Bencsik 1998, Unguean 1996) Duration: NM Treatment: NM Other: 6 relapsing–remitting, 1 first attack Other neurological disease: 3 F/ 3 M Mean age 31 (1-50) Disc, headache, HSV, neuropathy Healthy subjects: 12 su…”
BackgroundInfluentialLuppi, M., Barozzi, P., Maiorana, A., Marasca, R., Trovato, R., Fano, R., Ceccherini‐Nelli, L., & Torelli, G. (1995) · Journal of Medical Virology · doi:10.1002/jmv.1890470119 · Cited by 79
Self-citationFulminant human herpesvirus six encephalitis in a human immunodeficiency virus‐infected infant
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Current understanding of human herpesvirus 6 (HHV-6) chromosomal integration
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Successful Treatment of Human Herpesvirus 6 Encephalomyelitis in Immunocompetent Patient
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“HHV-6 is a neurotrophic virus present in brain tissues from healthy control patients (51), and more than (70%) of both MS patients and controls were positive for the representational difference analysis sequence by PCR (44).”
BackgroundHuman Herpesvirus-6: Neurologic Implications of a Newly-Described Viral Pathogen
Kimberlin, D. W., & Whitley, R. J. (1998) · Journal of NeuroVirology · doi:10.3109/13550289809113492 · Cited by 63
Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders
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“, the presence of late proteins expressed immediately after the replicative cycle–have not previously been investigated in brain tissue in psychiatric illness (Luppi et al., 1994; Challoner et al., 1995; Chan et al., 2001; Cuomo et al., 2001; Esposito et al., 2015).”
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Self-citationThe Presence of Human Herpesvirus 6 in the Brain in Health and Disease
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“The presence of HHV-6 in the brain has been repeatedly reported since the 1990s [37,38] and it is widely admitted in both immunocompromised and immunocompetent individuals.”
BackgroundHuman herpesvirus 6 encephalitis
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Modulation of the cytokine network in human adult astrocytes by human herpesvirus-6A
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“HHV-6 is present in different tissues including mononuclear cells, salivary glands, lungs, genital tract, brain and cerebrospinal fluid (CSF) (Braun et al., 1997; Cuomo et al., 2001; Luppi et al., 1994).”
BackgroundGenetic investigation of novel hantaviruses causing fatal HPS in Brazil
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“Furthermore, reports have suggested that HHV-6 may persist within the CNS [120] and that reactivation of HHV-6 may be associated with recurrent febrile seizures [118].”
BackgroundLack of Evidence for a Role of HHV-6 in the Pathogenesis of Alzheimer’s Disease
Agostini, S., Mancuso, R., Baglio, F., Cabinio, M., Hernis, A., Guerini, F. R., Calabrese, E., Nemni, R., & Clerici, M. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150464 · Cited by 39
“The possible role of HHV-6 in AD is highly controversial: thus, although a high frequency of HHV-6 genome was described to be present in AD brains [9], HHV-6 DNA is also observed frequently in the brains of non demented elderly individuals [7, 24].”
Herpes Viruses in Transplant Recipients: HSV, VZV, Human Herpes Viruses, and EBV
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“Nonetheless, other causes of encephalitis should be ruled out as HHV-6 has been detected in the CSF of asymptomatic patients and the symptoms of HHV-6 encephalitis may be strikingly similar to those of immunosuppression leukoencephalopathy.(172,179,180) Other manifestations of HHV-6 disease reported in the literature…”
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Case-Control Study of Primary Human Herpesvirus 6 Infection in Children With Febrile Seizures
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Risk of recurrent seizures after a primary human herpesvirus 6-induced febrile seizure
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A pilot study on the antibodies to HHV-6 variants and HHV-7 in CSF of MS patients
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“In children and adults with dual infections, only HHV-6A persists in CSF, which suggests that HHV6A had greater neurotropism, while HHV-6B tends to be more prominent in other tissues (Hall et al, 1998; Luppi et al, 1994).”
BackgroundImpact of human herpes virus 6 in liver transplantation
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Detection of human herpesviruses 6 and 7 genomic sequences in brain tumours.
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“Indeed, several studies have reported the presence of HHV-6DNA in different brain regions of healthy immunocompetent adults [5–11] as well as some viral transcripts, using in situ hybridization techniques [12].”
BackgroundThe pathogenesis of febrile seizures: Is there a role for specific infections?
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“However, although originally classified as lymphotropic herpesviruses, both HHV-6A and HHV-6B species have a considerably broader cell tropism as they can infect not only T- and B-lymphocytes but also macrophages [15], natural killer (NK) cells [16], vascular and lymphatic endothelial cells [17–19], epithelial cells o…”
BackgroundThe Interplay between Natural Killer Cells and Human Herpesvirus-6
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“…latent infectionwithHHV-6Barenot fully understood, several sites, including monocytes/macrophages [Kondo et al., 1991], salivary glands [Levy et al., 1990; Di Luca et al., 1995], and the central nervous system [Luppi et al., 1994], have been proposed as potential sites of latency.”
BackgroundInfections due to human herpesvirus 6 in solid organ transplant recipients
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An encephalitic episode in a multiple sclerosis patient with human herpesvirus 6 latent infection
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“…et al., 2001], but the pathogenic role of HHV-6 in those CNS diseases is dif®cult to establish since the viral DNA is also frequently found in normal CNS tissues [Luppi et al., 1994, 1995; Challoner et al., 1995; Merelli et al., 1997; Chan et al., 1999; Blumberg et al., 2000; Cuomo et al., 2001].”
BackgroundHerpes Viruses in Transplant Recipients: HSV, VZV, Human Herpes Viruses, and EBV
Shiley, K. T., & Blumberg, E. A. (2011) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2010.11.012 · Cited by 20
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Human Herpesviruses 6, 7, and 8
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“Human herpesvirus 6 can be silently harbored in the human brain following primary infection.(11) Detection of viTable.”
BackgroundVittayawacharin, P., E’leimat, G., Lee, B. J., Griffin, S. P., Doh, J., Nam, H. H., Blodget, E., Jeyakumar, D., Kongtim, P., & Ciurea, S. O. (2023) · Transplantation and Cellular Therapy · doi:10.1016/j.jtct.2023.02.022 · Cited by 17
Human herpesvirus 6 and the nervous system
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Leukotropic herpesviruses in multiple sclerosis
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Chromosomally-integrated human herpesvirus 6 in familial glioma etiology
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“While a few studies have provided limited evidence that HHV-6 virions are present in brain tumor tissues (8– 60% prevalence range) [24–27], whether the virus may play a causative role in a subset of cases remains unclear because the prevalence of the virus in tumor tissues is not consistently higher compared to normal…”
BackgroundTransactivation of Human Endogenous Retroviruses by Viruses
Evans, E., Saraph, A., & Tokuyama, M. (2024) · Viruses · doi:10.3390/v16111649 · Cited by 15
An Adult Case of Relapsing Human Herpesvirus-6 Encephalitis
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“or recurrent febrile seizures [2] or in healthy children and adults [13,14].”
BackgroundHuman Herpesvirus 6 and Human Herpesvirus 7
Yamanishi, K., & Mori, Y. (2009) · doi:10.1128/9781555815981.ch23 · Cited by 9
Case Report: A Case of Severe Clinical Deterioration in a Patient With Multiple Sclerosis
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“The same applies to infection and replication in the CNS; studies have revealed the presence of HHV-6 DNA even in healthy brain tissues (6).”
BackgroundGanea, O. A., Tilișcan, C., Streinu-Cercel, A., Pițigoi, D., Drăgănescu, A. C., Lazar, M., Mihai, N., Florea, D., Aramă, S. Ș., & Aramă, V. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13164660 · Cited by 7
“Similar to all herpesviruses, HHV-6 causes a primary infection, usually during the first two-three years of life, after which it becomes dormant predominantly inside monocytes and macrophages [3–5].”
BackgroundGuennec, L. L., Mokhtari, K., Chauvet, D., Dupuis, N., Roos‐Weil, D., Agut, H., Leclercq, D., Psimaras, D., Mayaux, J., Demeret, S., et al. (2017) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2017.04.003 · Cited by 7
A Practitioner's Guide to Human Herpesvirus-6 (HHV-6) and Human Herpesvirus-7 (HHV-7)
Caserta, M. T., & Hall, C. B. (1998) · AIDS Patient Care and STDs · doi:10.1089/apc.1998.12.833 · Cited by 7
“…the presence of HHV-6 DNA in the cerebrospinal fluid (CSF) of normal children and in brain tissue from adults dying from non-neurologic diseases.47,48 Whether the presence of HHV-6 DNA or proteins in the central nervous system of patients with neuropathologic lesions represents merely…”
HHV-6: an unusual cause of cerebellar ataxia
Sitta, E. A., Khazan, A., Luttmann, K. F., et al. (2020) · BMJ Case Reports · doi:10.1136/bcr-2020-234303 · Cited by 6
Rantala, H., Mannonen, L., Ahtiluoto, S., et al. (2000) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2000.tb00123.x · Cited by 6
“HHV-6 may invade the brain without causing any neurological symptoms (Luppi et al. 1994), and our finding of a HHV-6 genome in tumour tissue may indicate that the virus is capable of invading tumour tissue.”
BackgroundHuman herpesvirus-6 infection in a critically ill and immunocompetent patient: a case report
Chia, X. T., Wong, H. L. M., & Loh, J. S. (2024) · Journal of Medical Case Reports · doi:10.1186/s13256-024-04387-5 · Cited by 5
“HHV-6 also belongs to the subfamily betaherpesvirinaie , which is characterized by an established latency in leukocytes after the initial infection [2].”
Background
Metadata
- Authors
- Luppi, M., Barozzi, P., Maiorana, A., Marasca, R., & Torelli, G.
- Affiliations
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Torelli, G.
- Venue
- Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 1994-04-01
- Volume
- 169
- Issue
- 4
- Pages
- 943-944
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- OpenAlex
- W2325138701
- Cited by
- 130
- References
- 0
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Infectious Diseases › Herpesvirus Infections and Treatments
- Keywords
- human herpesvirus 6, viral latency, neurotropism
- MeSH terms
- Base Sequence, Brain, Carrier State, DNA, Viral, Herpesviridae Infections, Humans, Molecular Sequence Data, Herpesvirus 6, Human, Polymerase Chain Reaction, DNA Primers
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