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Microbiology
Virus Passes Acid Test for Entering Cells
Some experiments are so elegantly conceived and convincingly carried out—their results so widely embraced—that few people think to repeat them years later. A team of HMS scientists has done just that, with potentially paradigm-shaking consequences for virology. Not only do their results contradict previous findings, they overturn a central dogma about how viruses invade cells.
"We were so shocked by our findings that we really had to convince ourselves," said Walther Mothes (left), shown with co-author Adrienne Boerger. "I think now that previous experiments were not wrong but assumptions at the time were too narrow." —Graham Ramsay
To wangle their way into the cytoplasmic core of a cell, viruses must first fuse with the cellšs outer membrane. The intruders were thought to accomplish this critical step in one of two ways and in one of two locations—either through exposure to the acidic environment inside the balloonlike endosome within the cell or by binding to receptors on the cell surface.
The acid test for the first, or low pH, mode of entry was established many years ago in a classic series of experiments. Viruses such as HIV and avian leukosis virus (ALV) failed this test. So thorough seemed the experiments that a dogma quickly sprang up that viruses were either pH-dependent or receptor-dependent, a distinction that appeared to brook no middle ground.
Walther Mothes, Adrienne Boerger, and their colleagues recently repeated those classic experiments on ALV, using methods that enable them to scrutinize their viral subjects earlier in the infection process, and under more precise conditions. By their more refined measures, ALV passes the acid test—it depends on low pH to fuse—and it also depends on receptor interaction. So it requires both. The findings appear in the Nov. 10 Cell.
The discovery of a new hybrid category of viral fusion promises to shake up virology. To begin, it uproots the entrenched two-part classification system, and with it, much previous work in the field.
