The Oskar Fischer prize is named after a neuropathologist who was the first to describe neuritic plaques in 1907 in Prague. James Truchard, the former CEO and Chairman of National Instruments has donated funds for a prize to scientists who can review the existing medical literature to come up with a theory on what causes Alzheimer’s. Truchard points out that there have been 130,000 scientific papers on Alzheimer’s but that each paper focuses only on a narrow aspect of the disease and brain science. He wants someone to comb through all of the literature and find a unifying “big picture” explanation. “Just like someone like Einstein did in creating the theory of general relativity or Darwin did in looking at …
Research Priorities
Note: we welcome your input. Please send comments to: Kristin_Loomis@HHV-6Foundation.org PROPOSED NEW PRIORITIES FOR ALZHEIMER’S RESEARCH Exploration of HHV-6A and HHV-7 in the development and progression of Alzheimer’s Disease Background: Two recent papers published in Neuron have strongly implicated herpesviruses in the pathogenesis of Alzheimer’s disease. Moir and Tanzi showed that amyloid plaques develop rapidly in response to infection by HHV-6A, HHV-6B and HSV1 (Eimer 2018). In addition, a comprehensive NIH funded “multiomic” evaluation of the Alzheimer’s brain tissue using next generation sequencing data strongly implicated two roseoloviruses: HHV-6A and HHV-7 (Readhead 2018). Among the findings: Contrary to popular belief, HHV-6A is not ubiquitous. Only HHV-6B, which is spread via the saliva, is ubiquitous. HHV-6A is not found in the …
HHV-6A receptor CD46 identified as a critical factor in ‘awakening’ endogenous retrovirus
Both infectious and UV-inactivated HHV-6A activate endogenous retrovirus envelope protein – but so does selective stimulation of HHV-6A’s CD46 receptor. This “cross-talk” between HHV-6A and endogenous retrovirus appears to play an important role in the pathogenesis of inflammatory diseases.
New findings on how HHV-6A/B U94 blocks angiogenesis
The HHV-6 latency gene U94 has been found to block angiogenesis, but the mechanisms behind this phenomenon have been unclear. A team lead by Roberta Rizzo and Elisabetta Caselli in Italy shed light on this process, opening the door to new potential molecular targets to pursue in treating diseases marked by improper vascularization.
HHV-6A & B dysregulate autophagy differently in HSB-2 cells
A group led by Mara Cirone in Italy found that HHV-6B blocks autophagy in HSB-2 cells. Both HSV-1 and CMV have proteins that block autophagy, and HHV-6B carries genes that are homologues of those encoding for CMV’s anti-autophagy protein. Her next step is to study the impact of both HHV-6A and HHV-6B on autophagy in neuronal cells.
NEJM HIGHLIGHTS A CASE OF HHV-6 REACTIVATION IN DRESS
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.
