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Yasuko Mori awarded Lifetime Achievement Award

Yasuko Mori, PhD, Professor of Clinical Virology at the Kobe University Graduate School of Medicine was awarded the HHV-6 Foundation’s Dharam Ablashi Lifetime Achievement Award at the 11th International Conference on HHV-6 & 7.

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Biospecimen Repositories for Alzheimer’s Disease

NIH NeuroBioBank (brain tissues from various neurological diseases) BrainNet Europe – 19 brain banks in 11 European countries UK Brain Banks Network Australian Brain Bank Network – accepts requests from outside Australia

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Decreased HHV-6 IgG in Alzheimer’s

Investigators from Uppsala University in Sweden found that HHV-6 IgG reactivity was significantly lower in Alzheimer’s Disease patients compared to controls. The authors suggest reduced immunity may be one reason why past studies have found increased levels of HHV-6 DNA in the brains of Alzheimer’s patients compared to controls.

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CXCL11 and CCL2 are specific to HHV-6B in febrile infants

Japanese investigators from Kobe University identified CXC11 as a chemokine uniquely expressed in primary HHV-6B infections. They also confirmed a previous finding that cytokine CCL2 (MCP-1) plays a role in HHV-6B primary infections. Both CXCL11 and CCL2 are expressed in several neuroinflammatory conditions including epilepsy, Alzheimer’s disease and traumatic brain injury.

Elevated levels of HHV-6 DNA in Alzheimer’s, linked to variants in antiviral genes

A group from Italy’s University of Bologna report that genetic defects in antimicrobial defense mechanisms can leave some individuals vulnerable to sub-clinical infections that lead to cognitive decline as they age. They found variations in specific antiviral genes that correlate with HHV-6 DNA levels in brain tissue and blood from patients with Alzheimer’s disease.

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HHV-6 increases risk of an “idiopathic” pneumonia syndrome after HCT as does murine roseolovirus in a BMT mouse model. Early HHV-6 was also found to increase non-relapse mortality

Investigators from University of Michigan have demonstrated that murine roseolovirus is a useful homolog for the study of HHV-6 reactivation in lung disease. In a large retrospective study of HCT patients, they also found early HHV-6 reactivation to increase the risk of both idiopathic pneumonia syndrome and non-relapse mortality.

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New mouse model for HHV-6 & 7

Investigators at Washington University have sequenced a murine herpesvirus and determined that it is closely related to HHV-6 & 7. Named Murine Rosesolovirus (MRV), the virus causes severe depletion of CD4+ T cells and thymic necrosis in young mice. The authors believe that MRV will be a useful mouse model to study the impact of HHV-6 & 7 in humans.

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HHV-7 homolog found in the peripheral nerve ganglia of macaques

Virologists led by Serge Barcy, PhD at the Seattle Children’s Research Institute and University of Washington have identified a homolog for HHV-7 in pigtail macaques They were surprised to learn that it could be detected in the peripheral nerve ganglia, and hope to use their new animal model to explore how HHV-7 might play a role in demyelinating diseases.

Spotlight on Horvat & Reynaud from INSERM

Branka Horvat, MD, PhD, Director of Research at the International Centre for Infectiology Research in Lyon, France (INSERM), and her doctoral student Josephine Reynaud have recently published an important paper on a new transgenic mouse model

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GAD antibodies & HHV-6 limbic encephalitis – a case of molecular mimicry?

A fifth case of limbic encephalitis associated with GAD antibodies and HHV-6 infection has been reported, this time in an immunocompetent woman with chromosomally integrated HHV-6, epilepsy, and psychosis. The patient’s condition improved (with a drop in GAD antibody titers and stabilization of psychotic symptoms) in response to three weeks of antiviral therapy but relapsed when antiviral therapy was withdrawn.

Epstein-Barr Virus and Human herpes virus 6 Type A DNA Enhance IL-17 Production in Mice

Since both HHV-6 and EBV have been associated with an increased risk of autoimmune disease development, a group at the American University of Beirut studied whether viral DNA might be capable of triggering IL-17, a cytokine associated with autoimmune disease. They injected BALB/c mice intraperitoneally with either EBV or HHV-6A DNA. They found that both IL-17 and IL-23 were markedly elevated.

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HHV-6 DR7 found to promote glioma development and progression

A Chinese group found HHV-6 direct repeat 7 in 48% of glioma tumors. Furthermore, they determined that DR7 overexpression could promote glioma cell migration, invasion and angiogenesis. Expression profiles showed that DR7 created an inflammatory microenvironment that enhanced degradation of the extracellular matrix.

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HHV-6 in Cancer: Does it play a role?

Since its discovery, HHV-6 has been studied in the context of lymphoproliferative disorders and various types of cancer. Several obstacles, particularly the ubiquitous nature of the virus, have made it difficult to determine exactly how HHV-6 might, or might not, be involved in tumor development.

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Does the high level of U94 in iciHHV-6 contribute to abnormal ‘marker’ chromosomes and cancer?

Investigators from the University of Ferrara, Italy have found evidence suggesting that high levels of U94 in ciHHV6 may predispose to the formation of marker chromosomes. A patient with diffuse large B-cell lymphoma positive for inherited chromosomally integrated HHV-6A and HHV-6A was also found in a marker chromosome, an abnormal piece of chromosome that is seen in some leukemia and lymphomas.

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Foscarnet approved for HHV-6 encephalitis in Japan

Although foscarnet is widely used for HHV-6 encephalitis, it has never been specifically approved for HHV-6. Japan’s Ministry of Health, Labor and Welfare was the first to approve foscarnet (Foscavir) for the treatment of HHV-6 encephalitis.

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Multiple herpesvirus infections lead to telomere shortening

Investigators at Kings College London report that seropositivity for CMV, Herpes simplex 1 and HHV-6 are all associated with a significant shortening of telomeres over a three-year period. Furthermore, the magnitude of the changes was large. For example, CMV seropositivity was associated with the equivalent of almost 12 years of chronological age.

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Solo DR and non-telomeric chromosomal integration

A new study shows that HHV-6A direct repeats can survive alone in an integrated state without the rest of the viral genome. The study also identified non-telomeric integration of HHV-6A in both in vitro cultured cells as well as one iciHHV-6A patient.

Opinion: call for ciHHV6 screening in transplantion

Two physicians from Texas propose that ciHHV6 status of donors and recipients be determined before solid organ transplantion, using a single pre-transplant qPCR test on whole blood, and that patients with ciHHV-6 or ciHHV-6 donors be carefully monitored for signs of active HHV-6 infection.

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Does the high level of U94 in iciHHV-6 contribute to abnormal ‘marker’ chromosomes and cancer?

Investigators from the University of Ferrara, Italy have found evidence suggesting that high levels of U94 in ciHHV6 may predispose to the formation of marker chromosomes. A patient with diffuse large B-cell lymphoma positive for inherited chromosomally integrated HHV-6A and HHV-6A was also found in a marker chromosome, an abnormal piece of chromosome that is seen in some leukemia and lymphomas.

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Decreased HHV-6 IgG in Alzheimer’s

Investigators from Uppsala University in Sweden found that HHV-6 IgG reactivity was significantly lower in Alzheimer’s Disease patients compared to controls. The authors suggest reduced immunity may be one reason why past studies have found increased levels of HHV-6 DNA in the brains of Alzheimer’s patients compared to controls.

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Can depression, psychiatric disorders and fatigue be triggered by a neurovirulent latent HHV-6B protein?

Three virologists led by Kazuhiro Kondo, MD, PhD, a professor of virology at Jikei University School of Medicine, have filed a patent on a method to diagnose and treat prevent mood disorders which he says are initiated by latent and neurovirulent HHV-6B residing in glial cells, and that this condition can be treated effectively with nasal sprays, using the olfactory nerve as a route to the brain. Dr. Kondo has named this protein SITH-1 or “small protein encoded by intermediate state transcript”.

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HHV-6 induced Parkinsonism post-transplant

A group of researchers from Sao Paulo, Brazil reported the development of HHV-6 infection in the striatum of a 32-year-old man six weeks after allogeneic hematopoietic stem cell transplantation. This is the first reported case of HHV-6 infection affecting the striatum and presenting with Parkinsonism post-HSCT.

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HHV-6 reactivation tied to early hypogammaglobulinemia in drug hypersensitivity syndrome

A Spanish study of drug-induced eosinophilia found that early hypogammaglobulinemia was associated with subsequent HHV-6 reactivation in patients with severe drug hypersensitivity syndromes. This study of 274 cases at La Paz University Hospital in Madrid confirms earlier reports from Japan and France that described transient reductions of total IgG at the outset of drug hypersensitivity reactions leading to HHV-6 reactivation.

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Does CD134 upregulation explain why HHV-6 reactivates preferentially in DRESS/ DIHS?

It has long been a mystery why HHV-6 is preferentially reactivated in drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug induced hypersensitivity syndrome (DIHS). HHV-6 reactivation occurs in over 60% of severe cases and is part of the definition of DIHS in Japan. Investigators in Japan suspect that the explanation may lie with the CD134 receptor on activated CD4 cells.

HHV-6 induced kidney damage in drug hypersensitivity

A new case study suggests that HHV-6 might play a role in the multi-organ failure that often follows extreme cases of drug hypersensitivity. Although there have been many studies documenting HHV-6 viremia in drug hypersensitivity (DIHS/DRESS) cases, this is the first to examine an affected organ for signs of HHV-6 DNA and proteins. The mortality rate from severe drug hypersensitivity is approximately 10%, and death usually results from a late flare in symptoms and failure of one or more organ, typically the liver, kidney, lungs or heart. HHV-6 viremia occurs in the majority of extreme drug hypersensitivity cases (Pritchett 2012) but the reason for the disproportionate reactivation of HHV-6 is not understood. The case, which is presented by a Japanese …

Interview with Drs. Ishida and Shiohara

Drs. Ishida and Shiohara from Kyorin University in Tokyo have publised an inportant new study on the dynamics of herpesvirus reactivations during and after severe drug reactions. We asked them their thoughts on the implications of their findings.

Steroids increase HHV-6 but reduce EBV viral loads in DIHS/DRESS

In a recent study published in the European Journal of Allergy and Clinical Immunology, a group from Kyorin University School of Medicine in Tokyo sought to comprehensively record the dynamics of key herpesviruses beyond the acute stage of SJS/TEN. While EBV loads were higher in patients not receiving systemic corticosteroids, CMV and HHV-6 loads were higher in those receiving them.

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Oral brincidofovir cut the rate of high level HHV-6 viremia by 80%, suggesting that IV brincidofovir may have potential to prevent HHV-6 encephalitis.

An abstract at the Transplantation & Cellular Therapy Meeting in Houston showed that only 2% of 92 patients treated with oral brincidofovir developed high level reactivation compared to 11% of 61 patients taking the placebo. The results came from an analysis of stored samples from their previous Phase III SUPPRESS trial for CMV prophylaxis. Chimerix’s Phase III trial for cytomegalovirus failed. Although oral brincidofovir reduced CMV viremia during the first 14 weeks, CMV infections bounced back during the 10-week observation period that followed, and there was a higher mortality rate in the drug group. Analysts blamed the higher death rate on the inability of participating physicians to differentiate between bleeding (a side effect of the drug) and acute GVHD. Instead …

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Foscarnet prophylaxis reduces severity but does not prevent HHV-6 encephalitis

A Japanese trial of foscarnet prophylaxis in cord blood transplant patients was successful in reducing severity and mortality as well as suppressing high viral loads, but it failed to prevent encephalitis. The authors note that the blood brain barrier must be inflamed to allow effective penetration of the drug into the central nervous system and speculate that the prophylaxis may have protected the meninges.

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New study details devastating impact of HHV-6 encephalitis

Investigators in Japan studied 145 patients who developed HHV-6 encephalitis. At 100 days after transplantation, the overall survival rate was just 58.3%, compared with 80.5% for patients who did not develop encephalitis. High-dose antiviral therapy was shown to mitigate high mortality rates in these patients.

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HHV-6 induced amnesia after rituximab therapy for autoimmune disease

A young woman on rituximab and two other immunomodulatory agents for the treatment of dermatomyositis developed encephalitis with severe anterograde amnesia. As the use of biologic treatments for refractory autoimmune disease has been increasing, physicians are advised to consider HHV-6 and offer prompt antiviral therapy to limit irreversible morbidity.

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HHV-6 identified in 12% of simple and 42% of complex pediatric febrile seizures

Australian investigators studied 143 young children with febrile seizures for signs of viral infection and found that HHV-6 was the fifth most common virus after rhinovirus (22%), enterovirus (20%), adenovirus (21%) and influenza (13%). Overall, a virus was found in 71% of cases. Virus found in complex seizures was associated with HHV-6 (42%) or influenza (41%).

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GAD antibodies & HHV-6 limbic encephalitis – a case of molecular mimicry?

A fifth case of limbic encephalitis associated with GAD antibodies and HHV-6 infection has been reported, this time in an immunocompetent woman with chromosomally integrated HHV-6, epilepsy, and psychosis. The patient’s condition improved (with a drop in GAD antibody titers and stabilization of psychotic symptoms) in response to three weeks of antiviral therapy but relapsed when antiviral therapy was withdrawn.

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Pathogenic role for HHV-6B in in mesial temporal lobe epilepsy

Japanese investigators published findings suggesting that HHV-6B plays a pathogenic role in epilepsy by enhancing gene expression that induces neuroinflammation and sclerosis in the temporal lobe. HHV-6 DNA levels were significantly higher in the resected tissue of epilepsy patients with sclerosis compared to those without it.

High HHV-6B viral loads found in a subset of epilepsy brain resections

Investigators at the University of Bonn Medical Center in Germany have screened 346 fresh-frozen brain tissue resections from temporal lobe epilepsy (TLE) patients for all nine herpesviruses as well as for RNA viruses including Paramyxovirinae, Phleboviruses, Enteroviruses, and Flavivirus, using qPCR. HHV-6B was the only virus identified.

Interview with Dr. Pitt Niehusmann: HHV-6 & MTLE

Pitt Niehusmann has completed the largest study to date on the question of whether viruses play a role in refractory mesial temporal lobe epilepsy (MTLE), with 346 samples analyzed. We asked Pitt a few questions about his work.

HHV-6 status epilepticus in an immunocompetent adult

Immunocompetent adults are not supposed to get HHV-6 encephalitis or status epilepticus (SE) and HHV-6 testing is rarely performed in these patients. A new case report from Baylor suggests that testing for HHV-6 in these patients may be worthwhile.

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Oral brincidofovir cut the rate of high level HHV-6 viremia by 80%, suggesting that IV brincidofovir may have potential to prevent HHV-6 encephalitis.

An abstract at the Transplantation & Cellular Therapy Meeting in Houston showed that only 2% of 92 patients treated with oral brincidofovir developed high level reactivation compared to 11% of 61 patients taking the placebo. The results came from an analysis of stored samples from their previous Phase III SUPPRESS trial for CMV prophylaxis. Chimerix’s Phase III trial for cytomegalovirus failed. Although oral brincidofovir reduced CMV viremia during the first 14 weeks, CMV infections bounced back during the 10-week observation period that followed, and there was a higher mortality rate in the drug group. Analysts blamed the higher death rate on the inability of participating physicians to differentiate between bleeding (a side effect of the drug) and acute GVHD. Instead …

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Superinfection of HHV-6A in ciHHV6A patients with recurrent cardiac disease: a full genome analysis

A group led by Ursula Gompels from the London School of Hygiene & Tropical Medicine, University of London, did next generation sequencing on three ciHHV6A cardiac patients and found superinfections of HHV-6A in two of the three. They characterized the first full genome sequence of ciHHV-6A and demonstrated the inherited ciHHV6 genome was similar but distinct from known exogenous (community acquired) strains of HHV-6A .

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HHV-6 myocarditis, pericarditis following transplantation

A hematology group in Australia reported a case of biopsy-proven HHV-6 myocarditis post-hematopoietic stem cell transplantation (HSCT). he post-mortem exam confirmed dilated cardiomyopathy and focal changes consistent with viral myocarditis and cardiac tissue was positive for HHV-6 DNA by nested and quantitative PCR. Separately, A Japanese group reported a worman who developed pericarditis with over 10,000 copies/ml of HHV-6 DNA in the pericardial fluid, after a cord blood transplant.

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ciHHV-6 is a risk factor for angina pectoris

In an article published this month in the Proceedings of the National Academy of Sciences, Dr. Louis Flamand’s team has described a relationship between inherited chromosomally integrated HHV-6 (iciHHV-6) and the development of angina pectoris.

Heart failure worsens in patients with persistent HHV-6B positive biopsies

Numerous case reports and studies have now tied HHV-6 to myocarditis and cardiomyopathies. To further investigate this relationship, investigators from one of the top cardiology clinics in Europe performed a study to determine the outcome of patients discovered to have HHV-6 in their cardiac tissue during the initial biopsy screen.

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HHV-6 and EBV elevated in the GI tract of HIV+ patients

A group from Sapienza University in Rome has found a significantly elevated prevalence of HHV-6 and a higher viral load for EBV in the stomach and duodenum biopsies of patients with HIV compared to controls, suggesting that these viruses may contribute to the development of gastric cancer in immunocompromised patients.

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HHV-6A, infertility and miscarriage: a hypothesis

Growing evidence implicates HHV-6, especially HHV-6A, in some cases of female infertility, miscarriage, and other gestational problems affecting both the mother and child. The authors of the paper wonder if heparin, an anticoagulant with antiviral properties often used to treat infertility, might mitigate the detrimental effects of HHV-6 in the uterine environment.

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HHV-6A infection of the uterus linked to infertility

A new study reported that HHV-6A infects the lining of the uterus in 43% of women with unexplained infertility but cannot be found in uterine lining of fertile women.  Furthermore, the cytokine and the natural killer cell profiles were very different in patients with the infection. HHV-6A was found only in uterine endothelial cells, and not in the blood.

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HHV-6 is a greater risk than CMV for rejection in pediatric kidney transplantation

Investigators from the Children’s Hospital of Mexico found that although CMV caused the biggest increase in risk for liver rejection, HHV-6 was the more important infection associated with rejection of kidney transplants. A single HHV-6 infection resulted in an increased risk of over 5 fold, while a coinfection of EBV, HHV-6 and HHV-7 increased the risk of kidney rejection by over 17 fold.

HHV-6 induced kidney damage in drug hypersensitivity

A new case study suggests that HHV-6 might play a role in the multi-organ failure that often follows extreme cases of drug hypersensitivity. Although there have been many studies documenting HHV-6 viremia in drug hypersensitivity (DIHS/DRESS) cases, this is the first to examine an affected organ for signs of HHV-6 DNA and proteins. The mortality rate from severe drug hypersensitivity is approximately 10%, and death usually results from a late flare in symptoms and failure of one or more organ, typically the liver, kidney, lungs or heart. HHV-6 viremia occurs in the majority of extreme drug hypersensitivity cases (Pritchett 2012) but the reason for the disproportionate reactivation of HHV-6 is not understood. The case, which is presented by a Japanese …

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Yasuko Mori awarded Lifetime Achievement Award

Yasuko Mori, PhD, Professor of Clinical Virology at the Kobe University Graduate School of Medicine was awarded the HHV-6 Foundation’s Dharam Ablashi Lifetime Achievement Award at the 11th International Conference on HHV-6 & 7.

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HHV-6 DR7 found to promote glioma development and progression

A Chinese group found HHV-6 direct repeat 7 in 48% of glioma tumors. Furthermore, they determined that DR7 overexpression could promote glioma cell migration, invasion and angiogenesis. Expression profiles showed that DR7 created an inflammatory microenvironment that enhanced degradation of the extracellular matrix.

$4 million in prizes for literature reviews that explain Alzheiemer’s

The Oskar Fischer prize is named after a neuropathologist who was the first to describe neuritic plaques in 1907 in Prague. James Truchard, the former CEO and Chairman of National Instruments has donated funds for a prize to scientists who can review the existing medical literature to come up with a theory on what causes Alzheimer’s. Truchard points out that there have been 130,000 scientific papers on Alzheimer’s but that each paper focuses only on a narrow aspect of the disease and brain science. He wants someone to comb through all of the literature and find a unifying “big picture” explanation. “Just like someone like Einstein did in creating the theory of general relativity or Darwin did in looking at …

Research Priorities

Note: we welcome your input. Please send comments to: Kristin_Loomis@HHV-6Foundation.org PROPOSED NEW PRIORITIES FOR ALZHEIMER’S RESEARCH Exploration of HHV-6A and HHV-7 in the development and progression of Alzheimer’s Disease Background: Two recent papers published in Neuron have strongly implicated herpesviruses in the pathogenesis of Alzheimer’s disease. Moir and Tanzi showed that amyloid plaques develop rapidly in response to infection by HHV-6A, HHV-6B and HSV1 (Eimer 2018). In addition, a comprehensive NIH funded “multiomic” evaluation of the Alzheimer’s brain tissue using next generation sequencing data strongly implicated two roseoloviruses: HHV-6A and HHV-7 (Readhead 2018). Among the findings: Contrary to popular belief, HHV-6A is not ubiquitous. Only HHV-6B, which is spread via the saliva, is ubiquitous. HHV-6A is not found in the …

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HHV-6, EBV and CMV found in GI tract cancers

A group from Washington University used a bioinformatics system called VirusScan to analyze RNA-Seq data sets from 6,813 human tumors compared to those of adjacent normal tissue. Tumor samples representing 23 different forms of cancer were analyzed. HHV-6, EBV and CMV were found at significantly high levels in GI tract cancer tissue.

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Drug-induced liver injury and HHV-6 reactivation without rash or fever

Another case of drug induced liver injury accompanied by HHV-6 reactivation has been reported in Japan, the second such case without exanthema to be described. An earlier case was reported last year (Fujita 2015). The authors suggest that drug-induced liver injury cases be investigated for HHV-6 reactivation when liver dysfunction begins several weeks after the initiation of a new drug typically associated with hypersensitivity syndromes.

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HHV-6 increases risk of an “idiopathic” pneumonia syndrome after HCT as does murine roseolovirus in a BMT mouse model. Early HHV-6 was also found to increase non-relapse mortality

Investigators from University of Michigan have demonstrated that murine roseolovirus is a useful homolog for the study of HHV-6 reactivation in lung disease. In a large retrospective study of HCT patients, they also found early HHV-6 reactivation to increase the risk of both idiopathic pneumonia syndrome and non-relapse mortality.

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HHV-6 can cause “idiopathic” pneumonia

A pivotal study, led by Michael Boeckh at the Fred Hutchinson Cancer Research Center, has determined that occult infections contribute to 57% of all cases of “idiopathic” pneumonia syndrome (IPS), a condition previously assumed to be non-infectious. HHV-6 was the dominant pathogen representing 29% of cases.

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Latent HHV-6A may impair myelin repair in multiple sclerosis

A group at University of Rochester demonstrated that the HHV-6A latency gene, U94, inhibits migration of cells involved in myelin repair. Inefficient myelin repair is associated with progression MS, and the ability of HHV-6A to impede this process suggests that it could be involved in the progression of MS, and raises questions about the virus’s role in other chronic demyelinating diseases.

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New evidence linking HHV-6A U24 protein to MS

HHV-6 has been linked in numerous studies to multiple sclerosis. Now, investigators at the University of British Columbia have published new data suggesting that HHV-6A may be a key player in the development of multiple sclerosis. The investigators propose that the viral protein U24 may dysregulate myelination.

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CXCL11 and CCL2 are specific to HHV-6B in febrile infants

Japanese investigators from Kobe University identified CXC11 as a chemokine uniquely expressed in primary HHV-6B infections. They also confirmed a previous finding that cytokine CCL2 (MCP-1) plays a role in HHV-6B primary infections. Both CXCL11 and CCL2 are expressed in several neuroinflammatory conditions including epilepsy, Alzheimer’s disease and traumatic brain injury.

See All Multiple Sclerosis Articles
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Foscarnet approved for HHV-6 encephalitis in Japan

Although foscarnet is widely used for HHV-6 encephalitis, it has never been specifically approved for HHV-6. Japan’s Ministry of Health, Labor and Welfare was the first to approve foscarnet (Foscavir) for the treatment of HHV-6 encephalitis.

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HHV-6 increases risk of an “idiopathic” pneumonia syndrome after HCT as does murine roseolovirus in a BMT mouse model. Early HHV-6 was also found to increase non-relapse mortality

Investigators from University of Michigan have demonstrated that murine roseolovirus is a useful homolog for the study of HHV-6 reactivation in lung disease. In a large retrospective study of HCT patients, they also found early HHV-6 reactivation to increase the risk of both idiopathic pneumonia syndrome and non-relapse mortality.

View Post

HHV-6 is a greater risk than CMV for rejection in pediatric kidney transplantation

Investigators from the Children’s Hospital of Mexico found that although CMV caused the biggest increase in risk for liver rejection, HHV-6 was the more important infection associated with rejection of kidney transplants. A single HHV-6 infection resulted in an increased risk of over 5 fold, while a coinfection of EBV, HHV-6 and HHV-7 increased the risk of kidney rejection by over 17 fold.

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Virus-specific immunotherapy for transplant patients with primary immune deficiencies

A group from Baylor College of Medicine reviewed the efficacy of treating viral infections in transplant patients with primary immunodeficiencies using their viral-specific T lymphocytes. A total of 36 patients were treated with these immunotherapy infusions before or after undergoing hematopoietic stem cell transplantation, and a complete or partial antiviral response were seen in 86% of patients with CMV, 76% of patients with EBV and all patients with adenovirus or HHV-6.

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Foscarnet approved for HHV-6 encephalitis in Japan

Although foscarnet is widely used for HHV-6 encephalitis, it has never been specifically approved for HHV-6. Japan’s Ministry of Health, Labor and Welfare was the first to approve foscarnet (Foscavir) for the treatment of HHV-6 encephalitis.

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Foscarnet prophylaxis reduces severity but does not prevent HHV-6 encephalitis

A Japanese trial of foscarnet prophylaxis in cord blood transplant patients was successful in reducing severity and mortality as well as suppressing high viral loads, but it failed to prevent encephalitis. The authors note that the blood brain barrier must be inflamed to allow effective penetration of the drug into the central nervous system and speculate that the prophylaxis may have protected the meninges.

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Low dose emetine shows promise as a herpesvirus antiviral

Investigators at Johns Hopkins have determined that emetine, an older drug used to treat dysentery as well as to induce vomiting, is also effective against cytomegalovirus (CMV/HHV-5). Not only was emetine effective at an extremely low dose, it demonstrated a synergistic effect when combined with ganciclovir in a mouse model of CMV infection and it worked at a much earlier stage of viral replication than the drugs currently in use.

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Genome editing to clear latent herpesvirus infection

A group from the University Medical Center in the Netherlands has shown that new gene editing technology can be used to impair viral replication and clear latent herpesvirus infections. The group used a CRISPR-Cas system to target viral genetic elements that completely eliminated CMV and HSV1 replication. They were also able to clear latent EBV from transformed human tumor cells.

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