Herpes simplex virus 1 (HSV-1) provokes lymph vessel overgrowth in the eye by triggering an unexpected growth factor, report Wuest and Carr. And this cascade could be blinding.
Although HSV-1 infects 50–90% of people worldwide, it rarely causes substantial harm. Occasionally, however, the virus sneaks into the cornea during periods of reactivation, obscuring vision or causing blindness. The inflammatory response provoked by the infection includes new blood vessel growth, which may be partly to blame for the resulting eye damage. Clinical evidence suggests that new lymph vessels may also appear during HSV-1 eye infections.
VEGF growth factors drive inflammatory lymph vessel growth in other situations, such as wound healing and bacterial infection. In these situations, infiltrating macrophages secrete VEGF-C and -D, which bind to the VEGFR-3 receptor to trigger new lymph vessels. Here, Wuest and Carr find that HSV-1 induces lymph vessel growth without help from macrophages or the usual VEGF middlemen.
Instead, HSV-1–infected epithelial cells drove vessel growth by secreting VEGF-A. The new lymph vessels persisted after viral replication ceased and also remained functional, as soluble antigens drained from the cornea into the draining lymph nodes.
Blossoming vessels could escalate inflammation by allowing antigens access to draining lymph nodes. Nevertheless, HSV-1 may be wise to exploit VEGF-A. The factor blocks dendritic cell maturation, perhaps helping the virus to evade the ensuing immune attack.