Integrin v6 is an RGD-dependent receptor for coxsackievirus A9

Coxsackievirus A9 (CAV9), a member of the Enterovirus genus of Picornaviridae, is a common human pathogen and is one of a significant number of viruses containing a functional arginine-glycine-aspartic acid (RGD) motif in one of their capsid proteins. Previous studies identified the RGD-recognizing integrin v3 as its cellular receptor. However, integrin v6 has been shown to be an efficient receptor for another RGD-containing picornavirus, foot-and-mouth disease virus (FMDV). In view of the similarity in sequence context of the RGD motifs in CAV9 and FMDV, we investigated whether v6 can also serve as a receptor for CAV9. We found that CAV9 can bind to purified v6 and also to SW480 cells transfected with 6 cDNA, allowing expression of v6 on their surface, but it cannot bind to mock-transfected cells. In addition, a higher yield of CAV9 was obtained in 6-expressing cells than in mock-transfected cells. There was no similar enhancement in infection with an RGD-less CAV9 mutant. We also found 6 on the surface of GMK cells, a cell line which CAV9 infects efficiently by an RGD-dependent mechanism. Significantly, this infection is blocked by an antibody to v6, while this antibody did not block the low level of infection by the RGD-less mutant. Thus, integrin v6 is an RGD-dependent receptor for CAV9 and may be important in natural CAV9 infections. Coxsackievirus A9 (CAV9), a member of the Enterovirus genus of the Picornaviridae family, is a common human patho