A group from the National Institute of Neurological Disorders and Stroke, NIH, has reported finding Epstein-Barr Virus (EBV) and HHV-6 but no cytomegalovirus (CMV) in astrocytomas, a brain tumor comprising approximately one quarter of all gliomas diagnosed. The group used digital droplet PCR (ddPCR), a technique that is highly precise but less sensitive than nested PCR and immunohistochemistry, techniques that have been used in previous studies.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
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?
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.
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).