Biological Plausibility of a Link Between Arterial Ischemic Stroke and Infection With Varicella-Zoster Virus or Herpes Simplex Virus.

695 There are now 9 human herpesviruses (HHVs); the increase from 8 to 9 was caused by a recent decision to split HHV strains 6A and 6B into distinct species. The 9 species are subdivided into 3 subfamilies: alpha (herpes simplex virus [HSV] types 1 and 2 and varicella-zoster virus [VZV]), beta (cytomegalovirus, HHV6A, HHV6B, and HHV7), and gamma (Epstein-Barr virus and Kaposi sarcoma–associated herpesvirus [sometimes called HHV8]). These same herpesviruses have evolved with humankind around the world since the great migration of modern humans across the Mandeb Strait out of Africa ≈60 to 100 thousand years ago. In a report in this issue of Circulation, Elkind et al sought to determine whether any of 5 herpesvirus infections—HSV1, HSV2, VZV, cytomegalovirus, or Epstein-Barr virus—increased the risk of arterial ischemic stroke (AIS) in children ≤18 years of age. They conclude that HSV1 infection and, to a lesser extent, VZV infection may act as triggers for childhood AIS. This editorial examines the biological plausibility of that assertion on the basis of both a literature review and the known pathogenesis of infection with HSV, VZV, and the live attenuated varicella vaccine virus.