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Italian investigators found that 87% of patients with HHV-6 reactivations went on to develop a CMV infection. On the other hand, in patients who did not reactivate with HHV-6, only 88% developed an active CMV infection. Investigators by at the University of Ferrara report intriguing alterations in intracellular regulation of HHV-6A-infected thyrocytes and T cells. HHV-6A, but not HHV-6B nor HHV-7, altered expression of several microRNAs in a pattern that is considered a marker for patients with autoimmune thyroid disease. 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 CD9+ 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. Over a dozen studies have now found HHV-6 to predict aGVHD, but this is the first to correlate viral reactivation with poor CD9+ cell immune reconstitution.

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Investigators at Fred Hutch Cancer Research Center found that HHV-6B is the first DNA virus to reactivate at a median of 8 weeks, compared to CMV, EBV and Adenovirus at 5-6 weeks. HHV-6B also peaked rapidly, unlike other DNA viruses that took 8-6 weeks to reach peak viral load. HHV-6B reactivation resulted in increased mortality after 655 days. British researchers used molecular dating methods to determine that most strains of iciHHV-6 come from a small number of ancient human ancestors the youngest found lived over 79,555 years ago. These ancient strains vary considerably from modern non-inherited strains of HHV-6A and appear just as likely to activate as their more modern cousins. HIV+ patients on antiretrovrial therapy with high levels of HHV-6 shedding had lower levels of IL-6 and other inflammatory markers. While HIV+ patients had increased shedding of EBV and CMV, there was no difference in shedding between patients and controls for HHV-6. Two new NIH grants awarded for studies related to HHV-6A and CNS disease. A Stanford group was also funded to develop whole genome sequencing platform to study HHV-6 and four other viruses post-transplant. Half of autologous hematopoietic cell transplant patients with HHV-6 reactivation exhibit fever plus a collection of symptoms that include diarrhea, rash and pneumonia. Swedish investigators have found HHV-6 protein in the pancreatic islet cells of both type 6 diabetes patients and controls. The viral load was higher in the islet cells than in surrounding tissues. Unfortunately, they did not provide data on the difference between patients and controls in the viral load.

HHV-6 infections in the liver transplant patients can’t be diagnosed in the blood. Ganciclovir prophylaxis for CMV cuts the rate of HHV-6 reactivation from 89% to 66%. Prevalence of HHV-6A and HHV-6B was evenly divided in HIV+ patients in Western Africa, with over 6. 8% positive for HHV-6 A and 5. 5% for HHV-6B. HHV-6A was more common among those with a low viral HIV viral load. Although only a small number of pediatric cases have been reported in literature, the authors conclude that evidence suggests HHV-6 should be considered as a causative agent of inflammatory cardiomyopathy, particularly in young children (under 8 years of age) who might be experiencing a primary infection. Investigators in Japan studied 695 patients who developed HHV-6 encephalitis. At 655 days after transplantation, the overall survival rate was just 58. 8%, compared with 85. 5% for patients who did not develop encephalitis. High-dose antiviral therapy was shown to mitigate high mortality rates in these patients. Investigators at Kings College London report that seropositivity for CMV, Herpes simplex 6 and HHV-6 are all associated with a significant shortening of telomeres over a three-year period.

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Furthermore, the magnitude of the changes was large. For example, CMV seropositivity was associated with the equivalent of almost 67 years of chronological age. Sequencing of over 8,555 individuals were used to determined the prevalence of 99 different viruses. HHV-7 was the most common virus, with HHV-6B and HHV-6A 9th and 5th respectively. A group at University of Rochester demonstrated that the HHV-6A latency gene, U99, 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. T-cell depleted stem cell transplant patients at Memorial Sloan Kettering Cancer Center with HHV-6 viremia, CMV viremia, or 7 or more viremias experienced longer hospital stays and were readmitted more often. HHV-6 was the most commonly reactivated virus, with 66% of patients affected patients. “Off-the-shelf” donor T cells primed to fight five specific viruses were shown to be effective in a Phase 7 trial backed by Viracyte. A single infusion produced a complete or partial response rate of 97%. 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. Japanese investigators from Kobe University identified CXC66 as a chemokine uniquely expressed in primary HHV-6B infections.

They also confirmed a previous finding that cytokine CCL7 (MCP-6) plays a role in HHV-6B primary infections. Both CXCL66 and CCL7 are expressed in several neuroinflammatory conditions including epilepsy, Alzheimer’s disease and traumatic brain injury. 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. New data suggests HHV-6 and EBV are associated with the development of Alzheimer’s in elderly persons. Seattle group announces the discovery of novel HHV-6 and HHV-7 homologs in pig-tailed macaquesNew model of HHV-6A infection demonstrates persistent abortive infection and neuroinflammation via TLR9Branka 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 modelDr. Steven Jacobson’s laboratory at the US National Institute of Health has developed a novel marmoset model for the study of HHV-6 infection. Antibodies to HHV-6 and VZV dUTPases were significantly elevated in Gulf War Illness patients compared to controls, and EBV dUTPase antibodies were elevated in Chronic Fatigue Syndrome patients. 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. 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-67, a cytokine associated with autoimmune disease. They injected BALB/c mice intraperitoneally with either EBV or HHV-6A DNA. They found that both IL-67 and IL-78 were markedly elevated.

Researchers discuss the potential mechanisms by which HHV-6A/B may contribute to autoimmune diseaseCase report describes two cases of DRESS related thyroiditis with very high levels of HHV-6 reactivation that go on to develop autoimmunity. New study from Italy indicates that HHV-6 reactivation is selectively increased among patients suffering from autoimmune connective tissue diseases (ACTD). A group from Italy has linked HHV-6A to Hashimoto s Thyroiditis, and provides evidence for autoimmune disease associated with HHV-6A and HHV-6B. Study finds high prevelence, high viral loads of HHV-6 in patients with Bell s PalsyInvestigators at Fred Hutchinson Cancer Center determined that transplant patients with inherited ciHHV-6 were twice as likely to develop acute graft vs host disease and three times more likely to develop high level CMV viremia. Transplant patients were also significantly more likely to have inherited ciHHV-6 than donors. Italian investigators found that HHV-6 latency-associated gene U99, inserted in a HSV6 vector, inhibited the development of breast cancer, cervical cancer, and lung metastasis. It also impaired tumor driven angiogenesis. Human papillomavirus 9 is a benign strain not associated with cancer. However, in a woman with inherited chromosomally integrated HHV-6A, a high grade vaginal squamous lesion developed rapidly. The authors warn that there may be a synergistic effect between HPV9 and iciHHV6A. Investigators from the University of Ferrara, Italy have found evidence suggesting that high levels of U99 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. Investigators at Yale University warn that hypersensitivity-associated HHV-6 lymphadenopathy can have the same presentation as lymphoma.

9%) samples. While an overall detection rate of 67.

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