The NEJM rarely covers HHV-6, but did an excellent case history of this patient with HHV-6 reactivation in conjunction with DRESS. The patient was not treated with an antiviral in spite of a plasma HHV-6 DNA load of 112,836, extensive lymphadenopathy, rash and abnormal liver function tests. What did NEJM get wrong? They stated ciHHV6 could be ruled out because a) the viral load was only log 5 on a plasma DNA test and b) the viral load dropped to less than 500 copies/ml. The plasma viral load in a ciHHV-6 patient can fall below 500 copies/ml if the blood is centrifuged within a few hours. On the other hand, ciHHV-6 samples shipped overnight and centrifuged the next day, are …
Genomic analysis finds a surprising association between ciHHV-6 and two genes
A genomic analysis of samples from 141,431 Chinese women found a highly significant association between ciHHV-6 and a variant in the MLCI-MOV10L region. The MLC1 gene is involved in myeloid cell differentiation and the MOV10L1 gene may allow for more efficient integration during spermatogenesis.
Novel antiviral compound with unusual mechanism of action found to work well for HHV-6A and CMV
In a study led by Manfred Marschall German investigators analyzed the potency of novel pyrrolopyridine-class compounds and found one that is highly active against CMV and HHV-6A. It works at an early stage of viral protein production, and differs from ganciclovir in mechanism.
Active HHV-6A/B found in the cerebellar Purkinje cells in patients with mood disorders
HHV-6 was found more frequently in the Purkinje cells of bipolar and major depressive disorder patients compared to controls. Furthermore HHV-6A was associated with a reduced Purkinje cell size. HHV-6 was not found, however in patients with schizophrenia.
Could this be why HHV-6 is better than other herpesviruses at establishing latent infection?
German investigators suggest that silencing of HHV-6A by the ND10 complex may explain why HHV-6A is more likely than other herpesviruses to establish a quiescent infection.
HHV-6 small non-coding RNA proposed as an indicator of an early stage of HHV-6 reactivation
German investigators have identified a marker for what they believe is the earliest stage of viral reactivation, or “transactivation” marked by transcription of several viral small non-coding RNAs in the absence of detectable viral replication. The group believes that these viral small RNAs could be developed as biomarkers.
HHV-6 in the news!
After years of very little interest by the scientific community, there has suddenly been a lot of interest in HHV-6A, which along with HHV-7, appears to be central to the progression of Alzheimer’s disease.
HHV-6A IE1 antibodies associated with increased risk of non-Hodgkin lymphoma
Using a novel serological assay that can differentiate HHV-6A from HHV-6B, investigators found HHV-6A immediate early antibodies to be associated with an increased risk of non-Hodgkin lymphoma.
Cross-sectional analysis of CD8 T cell immunity to HHV-6B identifies new targets for adoptive T cell therapy
German investigators conducted a broad scale analysis of CD8 T cell responses to HHV-6B, identifying novel epitopes with potential for immunotherapy or vaccines. The strongest responses were directed against an epitope from IE-2.
Large scale sequencing effort of HHV-6B defines global diversity, finds new genes, and identifies changes due to viral culture
A gigantic sequencing effort by investigators at University of Washington has provided a wealth of new information about the HHV-6B genome, including important flaws of the reference strains currently in use.
HHV-6A sequences found in ovarian cancer tissues but not in controls
A broadscale investigation of the ovarian cancer oncobiome using a microarray system PathoChip found HHV-6A sequences at or near genes associated with tumorigenesis in ovarian cancer tissue samples.
HHV-6 infection of NK cells causes dramatic changes in miRNA and transcription factors that govern immune function
Italian investigators showed that HHV-6A and -6B infection of natural killer cells have a remarkable effect on the expression of miRNAs and transcription factors, which in turn control natural killer cell development, maturation and function.
Deep sequencing analysis finds HHV-6, CMV and EBV in a subset of stomach and colon cancers
A team at University of Pittsburgh analyzed a large database of deep sequencing data from tumor and control tissues to look for viral sequences in 22 different cancers. They were surprised to find several herpesviruses in gastrointestinal cancers but not in control tissues.
Could HHV-6 U94 attenuate tumor cell growth and metastasis?
Italian investigators found that HHV-6 latency-associated gene U94, inserted in a HSV1 vector, inhibited the development of breast cancer, cervical cancer, and lung metastasis. It also impaired tumor driven angiogenesis.
A more efficient form of latency? HHV-6A persistence depends on telomeric repeats, not circular episomes
Most herpesviruses maintain latency by forming circular episomes in the nucleus of the cell. Investigators in Germany have provided further evidence that HHV-6A relies on their telomeres, not circular episomes, to maintain a persistent latent infection by integrating into the host chromosome.
