Cytomegalovirus Infection Worsens Multiple Sclerosis, Study in Mice Shows

A cytomegalovirus infection triggers an increase in inflammatory and cytotoxic immune cells in mice with multiple sclerosis (MS), which leads to enhanced inflammation and loss of nerve-protecting myelin.

The study, “Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation,” was published in the journal Scientific Reports.

A cytomegalovirus (CMV) infection leads to chronic activation of the immune system. One result is an increase in the number of immune cells called CD4⁺CD28^null T-cells. High levels of this T-cell subgroup are associated with chronic inflammatory diseases.

Some previous studies have suggested a link between CMV infection and MS. But other studies have suggested that CMV-specific antibodies are associated with a better disease outcome, an increased age of disease onset, and decreased brain atrophy.

Researchers decided to see whether CMV is able to trigger an increase in CD4⁺CD28^null T-cells, and how the infection impacts MS disease progression. The team used both mouse models and in vitro, or laboratory, work with human blood samples.

They observed that blood with a CMV infection had higher levels of CD4⁺CD28^null T-cells than blood with no infection. The researchers also found that CMV peptides, or amino acids, increased the number of these cells in a lab.

CD4⁺CD28^null T-cells are inflammatory, toxic cells found in MS lesions. Researchers discovered an increase in the cells in a mouse model of MS, and noted a correlation between the higher number and the severity of the disease. The used the established experimental autoimmune encephalomyelitis (EAE) mouse model of human MS.

Since CD4⁺CD28^null T-cells accumulate in brain lesions in MS patients, researchers wondered whether CMV could contribute to demyelination in the spinal cord of mice with MS. Demyelination is the term used to describe the loss of myelin, a protective coating around nerve-cell projections known as axons in the central nervous system. Myelin damage is a hallmark of MS.

The team observed that CMV-infected EAE mice had more demyelination than a control group of mice.

Overall, the results show that the number of CD4⁺CD28^null T-cells increases in a mouse model of MS, and that the increase correlates with disease severity. Also, a CMV infection triggers an increase in the T-cells, worsening disease in EAE mice by exacerbating autoimmune-mediated inflammation and demyelination.