MS activity reactivates dormant Epstein-Barr virus study finds

A new study has found that dormant Epstein-Barr virus (EBV) is activated during multiple sclerosis (MS) relapses and triggers inflammation in different types of immune cells.

Researchers found that blocking the virus’ activation can lessen the inflammatory activity of the immune cells, which they say supports the theory that targeting dormant EBV may help treat MS.

Although most people are infected with EBV by the time they reach adulthood, it is known to be one of the biggest risk factors for developing MS. EBV causes glandular fever but it is also linked to several cancers. After the initial infection, the virus stays inactive inside B-cells, which are a type of immune cell. In some situations, however, they can switch to an active, or ‘lytic’, state and prompt a new round of infection.

The scientists examined B-cell lines from individuals infected with EBV to gain insights into how the virus impacts immune function. They studied samples from MS patients with active disease (evidenced by at least one lesion with active inflammation on MRI scans), samples from MS patients with stable disease (without active lesions), and samples from individuals without MS.

Their findings revealed that B-cells from people with active MS exhibited more active, lytic EBV activity compared to cells from healthy individuals or stable MS patients. This heightened lytic viral activity in B-cells during active MS was associated with increased levels of inflammatory markers in these cells.

As an initial test of this idea, the researchers used their cell models to evaluate three antiviral compounds that inhibit EBV lytic activity through different biological mechanisms. The results indicated that two of the compounds — foscarnet and tenofovir alenfenamide (TAF) — successfully reduced markers of B-cell inflammation. However, while foscarnet was toxic to the B-cells, TAF was not.

This finding “shows that the problematic inflammation signaling from lytic EBV can be selectively targeted in a way that demonstrably reduces damaging immune responses,” stated Paul M. Lieberman, PhD, director of the Wistar Institute’s Center for Chemical Biology & Translational Medicine and co-author of the study.

Additional experiments revealed that when EBV-infected B-cells were cultured alongside T-cells – another type of immune cell crucial in driving MS – treatment with TAF also reduced the inflammatory activity of the T-cells