Purkinje cells are a central part of the human cerebellum, the part of the brain that plays an important role in motor learning, fine motor control of the muscle, equilibrium, and posture but also influences emotions, perception, memory and language.
Scientists from the Institute for Virology and Immunobiology of the University of Würzburg and their US colleagues have now made a surprising discovery in these nerve cells.
They found a high infection rate of Purkinje neurons with the human herpes virus HHV-6 for the first time in patients with two types of psychiatric disorders: bipolar disorder and/or severe depression.
Human Herpesvirus 6 (HHV-6) is a set of two closely related herpes viruses known as HHV-6A and HHV-6B. HHV-6B infects nearly 100% of human beings, typically before the age of three and often results in fever, diarrhea, sometimes with a rash known as roseola.
Although rare, this initial infection HHV-6B infection can also cause febrile seizures, encephalitis or intractable seizures.
Little is known about the prevalence of HHV-6A or how it is acquired, but one small study found very low levels of HHV-6A in the saliva of half of healthy adults.
Like the other herpesviruses – Epstein Barr virus, chicken pox, herpes simplex – HHV-6 establishes life-long latency and can become reactivated later in life.
This reactivation has been associated with many clinical manifestations that can be seen in the “Associated Conditions” section of this site.
Reactivation can occur in the brain, lungs, heart, kidney and gastrointestinal tract, especially in patients with immune deficiencies and transplant patients.
In some cases, HHV-6 reactivation in the brain tissue can cause cognitive dysfunction, permanent disability and death.
Except in acute or initial infections, the viral DNA can typically be found only by biopsy, as it does not circulate in peripheral blood.
A growing number of studies also suggest that HHV-6 may play a role in a subset of patients with chronic conditions.
HHV-6A has recently been found in the uterus of women with infertility, in the thyroid tissue of patients with Hashimoto’s thyroiditis and has been suggested as a trigger for a subset of MS and chronic fatigue syndrome cases.
High levels of HHV-6B DNA in the brain biopsies of refractory epilepsy patients suggest the virus may play a role in a subset of those with this condition. HHV-6 has also been tied to febrile seizures and status epilepticus.
There is an urgent need for new technologies to detect these occult infections that are not apparent by standard quantitative PCR DNA testing methods, in order to prove or disprove the important disease associations that have been suggested.
The study was led by Dr. Bhupesh Prusty, group leader at the Department of Microbiology.
The scientists published the results of their study in Frontiers in Microbiology.
Virus-related inflammation in the brain
“Inherited factors have long been known to increase the risk of developing several types of psychiatric disorders including bipolar disorder, major depressive disorder, and schizophrenia,” Prusty explains.
But there is also strong evidence that environmental factors, particularly those that lead to neuroinflammation early in life, might play an important etiologic role in the pathogenesis of these disorders as well.
Viruses are such an environmental factor.
“Pathogens may disrupt neurodevelopment and cross-talk with the immune system at key developmental stages,” Prusty explains.
Children that are infected at a young age usually recover without any late complications. However, the viruses lie dormant (latent) in various organs and tissues including the central nervous system and the salivary glands and can be reactivated under certain circumstances, even after years.
Increased infection rate in two psychiatric disorders
Prusty and his team suspected the human herpesviruses HHV-6A and HHV-6B to play a key role in the genesis of psychiatric disorders.
So they studied two of the largest human brain biopsy cohorts from Stanley Medical Research Institute (USA) and what they found confirmed their assumption.
Researchers show for the first time that type HHV-6 viruses are capable of infecting neurons and possibly causing cognitive disturbances leading to psychiatric disorders.
The image is credited to University of Würzburg.
“We were able to find active infection of HHV-6 predominantly within Purkinje cells of human cerebellum in bipolar and major depressive disorder patients,” Prusty sums up the central result of their study.
The results show for the first time that type HHV-6 viruses are capable of infecting neurons and possibly causing cognitive disturbances leading to mood disorder.
According to the scientists, the study disproves the belief that viruses which lie “dormant” and hidden in organs and tissues never cause any disease.
“Studies like ours prove this thinking as wrong,” Prusty says and he cites another study which shows that Alzheimer’s disease can also be caused by human herpesvirus 6A.
In the next step, the Würzburg researchers want to figure out the molecular mechanisms behind HHV-6A mediated cellular damage to Purkinje neurons.
Dr. Bhupesh Prusty – Frontiers
The image is credited to University of Würzburg.
Original Research: Open access
“Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders”
Bhupesh K. Prusty, Nitish Gulve, Sheila Govind, Gerhard R. F. Krueger, Julia Feichtinger, Lee Larcombe, Richard Aspinall, Dharam V. Ablashi and Carla T. Toro Frontiers in Microbiology. doi:10.3389/fmicb.2018.01955