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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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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.

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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.

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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 …

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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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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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Human Herpesviruses-6A/6B linked to important reproductive diseases

A recent review from the Departments of Medicine and Obstetrics/Gynecology at Harvard Medical School and the University of Ferrara, Italy, summarizes evidence linking HHV6-A/B to several important reproductive diseases: primary unexplained infertility, preeclampsia, congenital infection and, possibly, spontaneous abortion and intrauterine growth restriction.

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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 …

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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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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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