Rotavirus Caught During Break-In

A recent study reveals how rotavirus, a nonenveloped virus that is the major cause of diarrhea in infants, rearranges its surface proteins to enable it to bind to and penetrate host cells.

Investigators at Harvard Medical School (Boston, MA, USA) used x-ray crystallography and electron microscopy to obtain images with a resolution of 3.2 angstroms. At this resolution they were able to observe that treatment of the rotavirus VP4 surface "spike” protein with digestive enzymes primed the virus for entry by triggering a rearrangement that rigidified the VP4 spikes. The crystal structure of VP4 demonstrated a coiled-coil stabilized trimer.

VP4 also underwent a second rearrangement, in which the oligomer reorganized, and each subunit folded back on itself, translocating a potential membrane-interaction peptide from one end of the spike to the other. This rearrangement resembled the conformational transitions of membrane fusion proteins of enveloped viruses. These study findings were published in the August 26, 2004, issue of Nature.

"This protein goes through some extraordinary gymnastics that are almost certainly related to its function,” said first author Dr. Philip Dormitzer, assistant professor of pediatrics at Harvard Medical School. "The outside layer is like a landing apparatus and is stripped off in the course of entry. Its job is to get the innermost portions--the genes and the replication machinery--inside the cell.”




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