When the research team led by Benedikt Kaufer attempted to shed light on the mechanism behind HHV-6 integration, they were suprised to find telomeric repeats were critical to the integration process. Since the U94 gene shares homology and biological properties with the adenovirus Rep68 gene responsible for viral integration into human chromosomes, U94 was considered the most likely candidate to mediate HHV-6 integration.
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.
The crystal structure of HHV-6B U14 defined
A group led by Yasuko Mori in Japan has analyzed the crystal structure of HHV-6B U14, an important accomplishment for the understanding of HHV-6. Human herpesvirus 6B encodes numerous tegument proteins that make up the viral matrix. One of these tegument proteins is U14. In addition to being necessary for viral propagation, it is able to regulate host cell responses by interacting with host factors such as tumor suppressor p53.
Congrats to Seth Frietze, PhD for winning an NIH grant to study ciHHV-6
Congrats to Seth Frietze, PhD of the University of Vermont for winning an NIH grant to study ciHHV6. Dr. Frietz and his team have developed a system to study HHV-6 latency and will study differential gene expression during viral integration as well as reactivation in response to triggering drugs such as HDAC inhibitors.
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.
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.
HHV-6 & 7 found in spinal fluid of immunocompetent children suspected of CNS infection
An Italian study on immunocompetent children with suspected CNS infections found HHV-6 and HHV-7 DNA in 4.2% and 4.8% of 304 cerebrospinal fluid (CSF) samples, respectively. Although once considered rare in the immunocompetent, recent studies with more sensitive methods have found HHV-6 in the CSF of 4-17% of immunocompetent children with seizures or suspected CNS infections.
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.
Mystery: Why was ciHHV-6A integration lost with tumor formation?
Nicola Royle’s laboratory at the University of Leicester in the UK has reported that a ciHHV-6A patient with an HHV-8-negative primary effusion-like lymphoma had fully integrated genomes in the blood, but lost the integration in the tumor. Did the release of HHV-6A genomes play a role in tumor formation?
76% of Ugandan infants acquire HHV-6B in the first year
A new study led by Soren Gantt, MD from the University of British Columbia and Lawrence Corey, MD of the University of Washington revealed risk factors for transmission and symptoms of primary human herpesvirus infections among Ugandan infants.
Saliva DNA load for HHV-6 (but not HHV-7) elevated in caregivers of patients with dementia
Investigators associated with a dementia center at Kobe University Hospital found that saliva HHV-6 DNA levels may serve as an objective marker for caregiver exhaustion. The saliva HHV-6 DNA levels in caregivers (log 3.04 copies/ ml) were significantly higher than in those of non-caregivers (2.78 copies/ml).
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.
Highlights from the 9th International Conference on HHV-6 & 7
A summary of the highlights from the 9th International conference on HHV-6 & 7, held in Boston in November 2015, has been published. This summary may be downloaded free of charge from the Foundation web site at this link, from May 25 through August 1st. Many thanks to Anthony Komaroff, MD and the Conference Co-Chairs Louis Flamand, PhD and Philip Pellett, PhD for preparing this summary and to the editors of the journal for making the summary available free of charge for this period.
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”.
HHV-6 as a cause of liver failure in an immunocompetent patient with hypersensitivity
A group from University of Chicago Medicine urged physicians to consider testing for HHV-6 in cases of unexplained liver failure in immunocompetent patients, especially those with skin rash and upper respiratory symptoms, citing evidence from past studies as well as their own recent case experience.