Possible synergy between chronic alcohol use and HHV-6B infection of substantia nigra in producing microglial activation
Dysregulation of the microRNA miR155 is associated with pathophysiological progression of Alzheimer’s disease. HHV-6A has been shown to suppress miR155.
Japanese investigators show that a protein expressed by latent HHV-6B in astrocytes, results in an influx of extra-cellular calcium, triggering the onset of depression.
HHV-6/7 DNA was found in the plasma of 19.6% of epilepsy patients compared to none of the controls. Protein expression indicating active infection was found in 53% of the HHV-6/7 positive patients.
This multiplex qualitative test for cerebrospinal fluid helps physicians diagnose HHV-6 encephalitis quickly, but interpretation must take into account imaging, ciHHV-6 status and other markers.
Researchers at the NIH used RNA-Seq cells from skin and blood to study the underlying mechanisms in DIHS/DRESS and identified both HHV-6 and JAK-STAT pathways as potential targets. Central memory CD4+T cells were enriched with HHV-6B.
A team led by Steven Jacobson, PhD at NINDS analyzed RNA-seq datasets from 901 brains, and found only 1.2% of Alzheimer’s patients and 0.4% of controls positive for HHV-6 RNA. They also found HHV-6 DNA in less than 4% of samples tested by ddPCR.
Two groups have challenged the widely-publicized 2018 study in 2018, that found increased HHV-6A & 7 abundance and an association with clinical and pathology scores in Alzheimer’s. The topic has become the focus vigorous debate.
Building on their prior work, an Italian team has shown that HHV-6A is able to induce dysregulation of autophagy in neurons and astrocytoma cells, increasing amyloid beta and tau production.
Karolinska Institute researchers developed a novel serological assay to determine that individuals with antibodies to HHV-6A early proteins are more likely to develop MS. HHV-6A antibodies were the highest in the presence of elevated EBV antibodies, suggesting that the two viruses could jointly contribute to the development of MS.
Investigators propose that the induction of endoplasmic reticulum stress, likely exacerbated by autophagy inhibition, could contribute to the immune suppression induced by HHV-6B in exanthem subitem patients.
A review of post-transplant cases found that the incidence of HHV-6 myelitis was 4.1%; symptoms of pruritus without rash, pain, numbness, dysuria and constipation are potential signs.
Japanese investigators evaluated cytokines and chemokines in the CSF and plasma in HHV-6 encephalitis patients with good and poor prognoses. They found IL-6, IL-7, MCP-1 to be elevated one week before onset, suggesting that these cytokines may be effective targets for intervention.
MIT examined transcription across tens of thousands of individual cells in both Alzheimer’s and healthy brains and found APOE strongly upregulated in the microglia and perturbation in myelination-related processes in multiple cell types including oligodendrocytes.
The cellular housekeeping function of autophagy may play a role in Alzheimer’s as dysfunction could result in the accumulation of amyloid. HHV-6A, HHV-6B and HSV1 can infect central nervous system cells and dysregulate autophagy.