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© The Rockefeller University Press, 0021-9525/2002/10/15 $5.00
The Journal of Cell Biology, Volume 159, Number 1, 15-15

Adenovirus takes the back door

Adenovirus (arrows) exits by breaking adhesions between cells. Welsh/Elsevier

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 released into the basolateral solution. The authors showed that the resultant binding of CAR disrupted cell–cell adhesion, thus allowing viral escape to the apical surface. Similar disruption of endothelial CAR may allow the virus to spread into the bloodstream.

The efficient spread of adenovirus is thus dependent on a replication step, which is not an option for most gene therapy vectors. Welsh suggests using chemicals such as calcium phosphate to induce uptake, or viruses such as adeno-associated virus type 5 that use apical receptors. Alternatively, calcium chelators such as EDTA can open the tight junctions allowing adenovirus to reach CAR. "When you open up the tight junction," says Welsh, "adenovirus works great."

Reference:

Walters, R.W., et al. 2002. Cell. 110:789–799.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 290K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?