UTHealth, UT Austin scientists shed light on viral infections
HOUSTON – (Jan. 14, 2013) – Researchers from The University of Texas Health Science Center at Houston (UTHealth) and The University of Texas at Austin report in Science that detailed changes in the structure of a virus as it infects an E. coli bacterium have been observed for the first time.
To infect a cell, a virus must be able to first find a suitable cell and then eject its genetic material into its host. This robot-like process has been observed in a virus called T7 and visualized by Jun Liu, Ph.D., assistant professor of pathology and laboratory medicine at the UTHealth Medical School, and his colleagues.
Liu, William Margolin, Ph.D. and Bo Hu, Ph.D., along with Ian Molineux, Ph.D., of UT Austin show that when searching for its prey, the virus briefly extends — like feelers — one or two of six ultra-thin fibers it normally keeps folded at the base of its head.
"We visualized viral infection with unprecedented details in three dimensions by using a cryo-electron microscope,” Liu said.
This is the first time that scientists have made actual images showing how the tail of the virus extends into the host — the very action that allows it to infect a cell with its DNA.
Once a suitable host has been located, the virus behaves a bit like a planetary rover, extending these fibers to walk randomly across the surface of the cell and find an optimal site for infection.
“The virus has landing gear and people thought it was always down,” said Margolin, professor of microbiology and molecular genetics at the UTHealth Medical School. “The landing gear goes up and down.”
At the preferred infection site, the virus goes through a major change in structure as it ejects some of its proteins through the bacterium’s cell membrane, creating a path for the genetic material of the virus to enter the host.
After the viral DNA has been ejected, the protein path collapses and the infected cell membrane reseals.
“Although many of these details are specific to T7, the overall process completely changes our understanding of how a virus infects a cell,” Molineux said.
For example, the researchers now know that most of the fibers are usually bound to the virus head rather than extended, as was previously thought. That those fibers are in a dynamic equilibrium between bound and extended states is also new.
Molineux said that the idea that phages “walk” over the cell surface was previously proposed, but their Science paper provides the first experimental evidence that this is the case.
“I first hypothesized that T7 made an extended tail more than 10 years ago,” said Molineux, “but this is the first irrefutable experimental evidence for the idea and provides the first images of what it looks like.”
The researchers used a combination of genetics and cryo-electron tomography to image the infection process. Cryo-electron tomography is a process similar to a CT scan, but it is scaled to study objects with a diameter a thousandth the thickness of a human hair.
Liu and Margolin are on the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston. Hu is a postdoctoral research fellow at the UTHealth Medical School.
Written by Lee Clippard, Communications Director, College of Natural Sciences, The University of Texas at Austin
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