The Presence of Human Herpesvirus 6 in the Brain in Health and Disease

Abstract

The human herpesvirus 6 (HHV‐6) ‐A and ‐B are two dsDNA beta‐herpesviruses infectingalmost the entire worldwide population. These viruses have been implicated in multipleneurological conditions in individuals of various ages and immunological status, includingencephalitis, epilepsy, and febrile seizures. HHV‐6s have also been suggested as playing a role inthe etiology of neurodegenerative diseases such as multiple sclerosis and Alzheimer’s disease. Theapparent robustness of these suggested associations is contingent on the accuracy of HHV‐6detection in the nervous system. The effort of more than three decades of researching HHV‐6 in thebrain has yielded numerous observations, albeit using variable technical approaches in terms oftissue preservation, detection techniques, sample sizes, brain regions, and comorbidities. In thisreview, we aimed to summarize current knowledge about the entry routes and direct presence ofHHV‐6 in the brain parenchyma at the level of DNA, RNA, proteins, and specific cell types, inhealthy subjects and in those with neurological conditions. We also discuss recent findings relatedto the presence of HHV‐6 in the brains of patients with Alzheimer’s disease in light of availableevidence.

Chronic Alcoholism and HHV-6 Infection Synergistically Promote Neuroinflammatory Microglial Phenotypes in the Substantia Nigra of the Adult Human Brain

“…HHV-6 (20) is an antibody that is raised against viral lysate and can be used to detect the HHV-6A and HHV-6B subtypes [ 61 , 62 ]. The presence of the respective antigens was determined either by using the HiDef DetectionTM HRP Polymer system (Cell Marque, Rocklin, CA, USA) and 3,3′ diaminobenzidine (DAB) tetrahydrochloride kit (DAB + Chromogen and DAB + Substrate buffer, Cell Marque, Rocklin, CA, USA) or the goat antimouse IgG (H + L) antibody, Alexa Fluor ® 488 conjugate (Thermo Fisher Scientific, Invitrogen, UK, 1:300).…”

The Influence of Virus Infection on Microglia and Accelerated Brain Aging

“…Finally, human herpes viruses, including herpes simplex (type 1, 2, 6), varicella Zoster and Epstein–Barr virus, which are DNA viruses, have also neurotropic properties, may infect the brain and induce chronic neuroinflammation and neurodegeneration [ 179 , 180 , 181 , 182 ]. There may be an association between brain infection with herpes viruses and accelerated aging, including dementia and Alzheimer’s disease [ 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 ].…”

Human Herpesvirus-6 and -7 in the Brain Microenvironment of Persons with Neurological Pathology and Healthy People

“…During persistent viral infection, clinical manifestations may frequently not even appear. However, the putative long term influence is associated with the central nervous system (CNS) diseases such as encephalitis, Alzheimer’s disease, multiple sclerosis, and has a role in tumorigenesis and mood disorders [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”