all Stephen C. Harrison stories

RNA sequence restrains fatal encephalitis

70652986 — Mon, 26 Mar 2007 06:25:17 -0400

One short sequence of RNA protected mice from deadly brain inflammation caused by West Nile virus and Japanese encephalitis virus, report Priti Kumar, Manjunath Swamy, and Premlata Shankar. The findings, which appear online and in the April 2006 PLoS Medicine, underscore the therapeutic potential of the fast-moving field of RNA interference. It has only been four years since scientists first showed that RNA interference, which protects plants, flies, and worms from viral infections, also works in mammalian cells. Now, at least two experimental siRNA therapies already have advanced to phase I safety trials in people. Short interfering RNA (siRNA) silences genes most commonly by triggering the destruction of RNA before proteins can be made.

Learning how the SARS virus spikes its quarry

70652986 — Mon, 26 Mar 2007 06:21:52 -0400

Structural images that show how the SARS virus's spike protein grasps its receptor may help scientists learn new details about how the virus infects cells and could also help in identifying potential weak points that novel drugs or vaccines could exploit.

A worldwide SARS (severe acute respiratory syndrome) outbreak in 2002-2003 affected more than 8,000 people and killed 774 before being brought under control. Public health experts worry about another outbreak of the virus, which originates in animals such as civet cats.

The research team, led by Howard Hughes Medical Institute investigator Stephen C. Harrison at Children's Hospital and Harvard Medical School, and colleague Michael Farzan, also at Harvard Medical School, reported its findings in the September 16, 2005 issue of the journal Science.

Scientists reveal key clue to how HIV infects cells

50443248 — Wed, 25 Jul 2007 14:37:16 -0400

Harvard researchers have shown for the first time the critical "before" structure of an AIDS virus protein that plays a key role in the virus' infection of cells.
The protein, called gp120, is responsible for binding to target immune system cells. Once the protein binds to the cell, it changes its shape, allowing a second protein to fuse with the cell membrane and permitting infection to occur.

Images reveal how leading cause of severe childhood diarrhea enters cells

70652986 — Mon, 26 Mar 2007 06:18:51 -0400

The work illustrates how vaccine development can advance by probing the physical architecture of viruses and finding the parts needed to prime the immune system.

Rotavirus, which causes severe diarrhea and vomiting, infects most children, causes gastroenteritis that sometimes requires hospitalization, and kills about 440,000 children each year. The only licensed vaccine, RotaShield, was discontinued following reported cases of a condition causing bowel obstruction.

Research team leader Philip Dormitzer says of the outside layer of rotavirus that "its job is to get the innermost portions inside the cell."

From the outer layer project clusters of VP4 molecules, which Dormitzer's team trimmed down, crystallized, and diffracted using X-ray diffraction to determine their structures. VP4 undergoes shape changes that allow it to breach the membrane of the cell it's trying to infect.

First, when rotavirus arrives in the intestine, the VP4 molecules prime the virus to attack the cell. Then, VP4 breaks a hole in the cell membrane, letting the virus enter.

"The work is a clear example of the way in which structural studies can contribute to new good ideas about strategies for vaccines," says Senior Investigator Stephen Harrison, Ph.D.

3-D images reveal key step in viral entry into cells

70652986 — Mon, 26 Mar 2007 05:35:03 -0400

Work published in the Jan. 22, 2004, issue of Nature is a significant advance in the understanding of how viruses cause infection, and offers two possible strategies for blocking these infections with antiviral drugs or vaccines. The research involved a major category of viruses known as "enveloped" viruses, so called because of their fatty outer membrane. Class 1 enveloped viruses include influenza and HIV; the new research focuses on class 2 enveloped viruses, responsible for causing dengue fever, West Nile fever, hepatitis C, tick-borne encephalitis, Japanese encephalitis, and other lesser-known diseases. "Many of these are emerging infections," notes Stephen Harrison, a Howard Hughes Medical Institute investigator and chief of the laboratory of molecular medicine at Children's Hospital, who was the senior investigator on the study. Led by Yorgo Modis, a structural biologist and postdoctoral fellow in Harrison's laboratory at Children's Hospital, the researchers used X-ray crystallography to study a key envelope protein that sits on the membrane of the dengue virus. By aiming an X-ray beam through a crystallized form of the protein, they obtained three-dimensional images, precise down to the atom, showing how a shape change in the protein causes fusion to happen.