The human cytomegalovirus (HCMV) switches off its own replication after infection to stay off the immune system's radar. Unlike other dormant viruses that require a weakened immune system to reactivate, HCMV thrives amidst a roaring immune response. The virus replicates when its host cells—monocytes and other inflammation-causing cell types—proliferate. These cells produce cytokines such as TNF that directly stimulate the promoters of some HCMV genes.
Active HCMV infections are thus commonly found within the inflamed tissues of patients suffering from chronic inflammatory diseases, such as atherosclerosis. But whether the reactivated virus is just a lucky beneficiary of local inflammation or actively perpetuates inflammation was under debate.
Qui et al. now find that HCMV enhances inflammation by coercing nearby noninflammatory cells to join the fray. Smooth muscle cells isolated from inflamed tissues harbored active HCMV and produced leukotrienes—powerful proinflammatory lipids. Leukotriene production had been thought to be restricted to immune cells. How the virus reprograms the previously harmless muscle cells to become inflammatory is not clear.
The virus's escalation of inflammation probably amplifies its own growth and spread; smooth muscle cells, monocytes, and other HCMV host cells migrate when activated and might thereby seed new sites of viral activity.