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9/4/2001

Caveolae Offer Pathogens Easy Entry into Cells

Kate Traynor

Tiny cell-surface pits called caveolae seem to offer some pathogens, such as the human immunodeficiency virus (HIV), an easy way to enter and take up residence in host cells, say researchers.

According to a review article in the Aug. 24 issue of Science, caveolae give invading organisms a way to get inside host cells without encountering destructive enzyme-filled lysosomes. Thus, organisms that enter cells through caveolae can reach their intracellular destination intact and not have to be capable of defending against enzymatic degradation.

Besides HIV, pathogens that may invade cells through caveolae include the respiratory syncytial virus (RSV), mycobacterial species, and the parasites Toxoplasma gondii and Plasmodium falciparum. And recent research suggests that cholera and Helicobacter toxins can make use of caveolae to gain entry into host cells.

This cell-entry mechanism differs from the traditional process of endocytosis, which involves the activation of cell-surface receptors by an invading organism and subsequent engulfment of the invader. Once the pathogen is taken into the cell, lysosomes fuse with and release hydrolytic enzymes into the pathogen-containing pocket.

Caveolae may offer more than a point of entry into cells. Once inside a caveola, some invading pathogens seem to be directly transported to their preferred site in or across the cell. HIV, for example, is transported across epithelial cells through caveolae, RSV is shunted to the endoplasmic reticulum, and cholera toxin travels to the Golgi apparatus.

Although the exploitation of caveolae by pathogens can be harmful to the host, the structures probably evolved for beneficial purposes. Caveolae appear to play a role in transporting cholesterol between cells and may be involved in tumor suppression. And caveolae are also believed to regulate cellular activity through the signal-transduction process.

Research into caveolae could conceivably uncover ways to use these intracellular transport vehicles to deliver drugs or gene-transfer therapies into target cells. The review article’s authors urge that new studies be undertaken to learn more about caveolae and how they work.