NEW RESEARCH

 

The below article is pretty academic. For those of you that love research this one’s for you. For those of you that just want a summary feel free to skip to the last couple of paragraphs.

Cytomegalovirus (CMV) infection is prevalent worldwide, infecting an estimated 60% of the population in developed countries, and up to 100% of the population in developing countries.[1] Infection can occur at any age; in the US, up to 25% of children are infected by the age of five, and more than 50% of the population is infected by age 40.[2] 

CMV persists in certain cell types, such as cells in bone marrow and circulating immune cells. CMV infection, a subset of the herpes virus family is lifelong, although in healthy individuals, the virus mostly persists in a latent form, and is also kept in check by normal immune surveillance. The majority of infected individuals show no signs or symptoms.

CMV can become reactivated, however, when the immune system becomes compromised, or under inflammatory conditions. The colon is the most common site of CMV infection upon viral reactivation, where it may cause or further exacerbate inflammation. For example, CMV is often reactivated in inflamed colonic mucosa in ulcerative colitis patients, [3] who are often on immunosuppressive therapy.

Until recently, the role of CMV in promoting intestinal inflammation was unclear, but a recent study has shed new light on a potentially important mechanism.[4] ;In the study, CMV was shown to interfere with an anti-inflammatory immune factor that normally blocks intestinal macrophages (a type of immune cell) from becoming pro-inflammatory.

In healthy individuals, intestinal macrophages are usually non-inflammatory, and are regularly replenished by other circulating immune cells called monocytes that develop into non-inflammatory macrophages in the intestine. In CMV-infected individuals, however, reactivation of the virus can initiate a process that causes monocytes to develop into pro-inflammatory intestinal macrophages.

Within macrophages that develop from CMV-infected cells, the virus promotes an increase in the production of a gene that produces a protein that blocks signaling by the transforming growth factor beta (TGFbeta), an anti-inflammatory cytokine produced in the intestinal mucosa. TGFbeta normally blocks the expression of the important pro-inflammatory factor, NFkB, in intestinal macrophages. The end result of the CMV-stimulated increase in this harmful protein is increased intestinal inflammation.

CMV – a member of the herpes family – is a common viral infection that causes mild flu-like symptoms in healthy people but can lead to more serious illness in those with compromised immune systems.

Between 50 and 80 percent of people in developed countries are infected with CMV.  Although normally innocuous, given the right genetic background, chronic viral infection with CMV can trigger autoimmunity.

“Sjogren’s syndrome (SS) is the second most common autoimmune disease in humans, affecting up to three per cent of the population or more than four million people in the United States alone,” Professor Degli-Esposti said.

“It affects the function of salivary and lacrimal glands and leads to a debilitating disease characterised by the loss of saliva and tear production.”

Overwhelmingly, it is a disease suffered by women, with most symptoms of the disorder emerging in the 40 to 60 year age group.

It was previously known that inflammation  is essential for replication of CMV. This new study provides a key piece of the puzzle by demonstrating that CMV not only promotes inflammation, but also its own replication, by stopping a critical anti-inflammatory factor that normally keeps inflammation in check in the gastrointestinal tract.

 REFERENCES

  1. Griffiths et al.,The pathogenesis of human cytomegalovirus.  J Pathol 2015; 235: 288–297
  2. Centers for Disease Control and Infection (CDC), Cytomegalovirus (CMV) and Congenital CMV Infection. Article accessed on 23 Jan. 2019 from the CDC website: https://www.cdc.gov/cmv/overview.html
  3. Pillet et al., Cytomegalovirus and ulcerative colitis: Place of antiviral therapy. World J Gastroenterol. 2016 Feb 14;22(6):2030-45
  4. Dennis et al., Cytomegalovirus promotes intestinal macrophage-mediated mucosal inflammation through induction of Smad7. Mucosal Immunol. 2018 Nov;11(6):1694-1704