New Mechanism for Virus-Triggered Autoimmunity Uncovered

Very recommendable!

Perhaps thanks to the global SARS-CoV-2/Covid-19 pandemic there is more research into viruses! It appears that viruses are the cause of a lot more trouble to human health than has previously been realized!

"... Nearly everyone has been infected at some point with the human roseoloviruses HHV-6 and HHV-7. The resulting illness is usually a childhood infection that is characterized by a few days of high fever followed by a rash, but the virus sticks around in the body after those acute symptoms resolve. Previous research has suggested that roseolovirus infection  plays a role in autoimmune diseases, and more recent studies suggest human roseolovirus may be a trigger for the severe autoimmune disorder systemic sclerosis. However, few animal models have been available to try to tease out possible mechanisms for that particular link.  ...
Two well-explored explanations for autoimmunity after viral infection are molecular mimicry and the bystander effect. In molecular mimicry, similarities between a viral protein and a cellular protein result in immune cells mistakenly attacking the body, while in the bystander effect, the high level of inflammation induced by viral infection activates immune cells and leads them to attack healthy tissue. Neither mechanism is likely at work here ...
In addition, it turned out to be more than the stomach that was under attack. “We saw auto-antibodies to a wide range of other targets, which suggested to us that there might be a broader auto-immune response that’s occurring after neonatal infection,” ... The researchers therefore focused on the thymus, the organ in which T cells are trained not to go after the body’s own cells. They found that some of the mechanism of this central tolerance appeared to be disrupted by roseolovirus infection, resulting in the release of autoreactive T cells that then attacked the stomach. ..."

Blogger footnote: Why the article above referred to the rosoleovirus as HHV-6 and HHV-7 appears misleading: "Roseolovirus is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae." (source1, source2)

From the abstract:

"Infections with herpesviruses, including human roseoloviruses, have been proposed to cause autoimmune disease, but defining a causal relationship and mechanism has been difficult due to the ubiquitous nature of infection and development of autoimmunity long after acute infection. Murine [mouse] roseolovirus (MRV) is highly related to human roseoloviruses. Herein we show that neonatal MRV infection induced autoimmune gastritis (AIG) in adult mice in the absence of ongoing infection. MRV-induced AIG was dependent on replication during the neonatal period and was CD4+ T cell and IL-17 dependent. Moreover, neonatal MRV infection was associated with development of a wide array of autoantibodies in adult mice. Finally, neonatal MRV infection reduced medullary thymic epithelial cell numbers, thymic dendritic cell numbers, and thymic expression of AIRE and tissue-restricted antigens, in addition to increasing thymocyte apoptosis at the stage of negative selection. These findings strongly suggest that infection with a roseolovirus early in life results in disruption of central tolerance and development of autoimmune disease."

New Mechanism for Virus-Triggered Autoimmunity Uncovered | The Scientist Magazine® Roseolovirus infection disrupts how the body trains immune cells not to attack itself, a mouse study shows.

Disruption of thymic central tolerance by infection with murine roseolovirus induces autoimmune gastritis (open access)