HHV-6 Research News - November 2015
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HHV-6 reactivation reduces CD8+ T cell recovery with increased risk of infections and reduced survival

In a French study of 366 adult allogenic hematopeietic stem cell transplantation (aHSCT) recipients CD8+ T cell recovery was significantly reduced in patients with HHV-6 reactivation. HHV-6 reactivation was also associated with reduced survival and increased infections of CMV and BKV. The authors note that recent in vitro data has shown that HHV-6 infection can shift T-cell differentiation toward HHV-6 specific regulatory T cells known for potent immunosuppressive activity. This report also supports previous studies demonstrating higher non-relapse mortality in active HHV-6 infection after transplantation.
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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). The 62-year old patient had a relatively low HHV-6 DNA viral load (<200 copies/mL of plasma) three days before the patient passed away due to progressive heart failure on day +30. The 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. Immunohistochemistry revealed HHV-6 antigen in cardiac myocytes.
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, enterovirus and parvovirus B-19 DNA found in blood of immunocompetent infants with myocarditis

80% of infants with myocarditis were positive for a cardiotropic virus compared to less than 4% of healthy controls, according to a multicenter study led by researchers at Washington University in St. Louis. This was a far higher rate than in older children who had comparable levels of positivity.
Out of the 21 patients, 9 (43%) demonstrated positive blood viral PCR results: 4 were positive for enterovirus, 2 for parvovirus B19, 1 for adenovirus, and 2 for HHV-6. This is the first study to demonstrate an age-specific difference of viral DNAemia in pediatric patients with clinical myocarditis.
Read more.
Stanford uses non-invasive new assay to detect occult infections including HHV-6 after lung transplantation

Researchers from Stanford University successfully used circulating cell-free DNA (cfDNA) to identify infections in lung transplants that can often be found only with a more invasive transbronchial biopsy. Infections were identified by comparing nonhuman cfDNA with known genomic databases of pathogens.
This hypothesis free approach led to find HHV-6 & 7 at high levels in patients with infections, even though these viruses are not generally considered lung pathogens.
Read more.
HHV-6 induced Parkinsonism post-transplant

A group of researchers from Sao Paulo, Brazil  published a case study detailing the development of HHV-6 infection in the striatum of a 32-year-old man with diffuse large B-cell non-Hodgkin’s lymphoma. Six weeks after allogeneic hematopoietic stem cell transplantation, he developed progressive bilateral bradykinesia, rest tremor, upper limbs rigidity, and disorientation. HHV-6 was detected in both plasma and CSF by polymerase chain reaction (PCR). After being treated with intravenous ganciclovir, (5 mg/kg twice daily for 21 days) the patient demonstrated improvement in disorientation and a repeat CSF HHV-6 DNA PCR was negative at two weeks. This is the first reported case of HHV-6 infection affecting the striatum and presenting with Parkinsonism post-HSCT.
Read more.

The 9th International Conference on HHV-6 & 7  takes place November 9-11th in Boston at Harvard Medical School's Martin Conference Center.

Featured speakers include Lasker prize winner Stephen Elledge on DNA Damage Response & Viral Infection, Michael Boeckh on HHV-6 & Lung Disease, Jeffrey Cohen on HHV-6B in Febrile Seizures and MTLE. Read more.

Other Recent HHV-6 Publications:

Determinants of Human CD134 Essential for Entry of Human Herpesvirus 6B.

Human Herpesvirus-6 U14 Induces Cell-Cycle Arrest in G2/M Phase by Associating with a Cellular Protein, EDD.

Drug-Induced Hypersensitivity Syndrome Followed by Subacute Thyroiditis.

Optic neuritis as an initial manifestation of human herpesvirus 6 reactivation after unrelated bone marrow transplantation.

Increased risk of infections and infection-related mortality in children undergoing haematopoietic stem cell transplantation in comparison to conventional anticancer therapy: a multicentre nationwide study.

Human herpesvirus-6 viremia is not associated with poor clinical outcomes in children following allogeneic hematopoietic cell transplantation.

Human herpesvirus-6 associated with hematopoietic stem cell transplantation.

The Role of Cytokines, Chemokines, and Growth Factors in the Pathogenesis of Pityriasis Rosea.

Serologic evidence that activation of ubiquitous human herpes virus-6 (HHV-6) plays role in chronic idiopathic/spontaneous urticaria (CIU).

Atypical exanthems associated with HHV-6 reactivation after hematopoietic cell transplantation.

Distinguishing the status of human herpesvirus 6 and 7 infection.

Individuals with inherited chromosomally integrated HHV-6 (ciHHV-6) have functionally active HHV-6 specific T-cell immunity.

Astute Clinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 of ICOS Causes a Combined Immunodeficiency Associated with an Enteritis and Hepatitis.

Ganciclovir-resistant HHV-6 encephalitis that progressed rapidly after bone marrow transplantation.
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