Adenovirus takes the back door

It has puzzled and frustrated gene therapists that their early workhorse, adenovirus, uses a receptor that is largely inacessible. CAR, an adhesion protein that serves as the adenovirus receptor, is located on the basolateral surface of the lung epithelium, and is thus hidden from incoming virus. But now Robert Walters, Michael Welsh (University of Iowa, Iowa City, IA), and colleagues report that this strange arrangement helps adenovirus to spread infection by breaking up the epithelium.

Entry may remain a scattershot affair for adenovirus. “I think it's intermittent [epithelial] breaks that all of us must have that gives the initial entry,” says Welsh. These hypothetical micro-injuries would allow the adenovirus capsid protein called Fiber to bind CAR on the basolateral surface.

After replication, large numbers of viral particles, defective viral particles, and excess Fiber protein are all...