A new study shows that HHV-6A direct repeats can survive alone in an integrated state without the rest of the viral genome. The study also identified non-telomeric integration of HHV-6A in both in vitro cultured cells as well as one iciHHV-6A patient.
The group that recently discovered a ligand for U24 has expanded upon their previous experiments to further elucidate the viral protein’s interactions and functions as they pertain to MS.
A group led by Professor Niza Frenkel of Tel Aviv University in Israel has determined that HHV-6A limits its own replication to avoid detection and destruction, leading to a long life-cycle with limited propagation. This finding may reveal the mechanism behind persistent HHV-6A infections and help explain some disease associations.
A group from Aarhus University propose that differing isoform patterns of CD46 correlate with the ability of some HHV-6B strains to enter T cells.
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.
Chinese investigators from Nanjing Medical University report that HHV-6A infection of astrocytes are associated with differences in gene expression that are also found in several CNS diseases including Alzheimer’s, glioma and multiple sclerosis. The investigators used gene ontology analysis to determine the biological processes, cellular components, and molecular functions of the differentially expressed genes and signalling pathways.
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.
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.
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.
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.
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?