Virus discovery holds mystery, potential

Date posted: February 7, 2012

Espirto Santo virusPhoto courtesy of Dennis BrownThis is a composite image of the Espirto Santo virus. The orange sphere is a three-dimensional reconstruction of the virus made from electron micrographs. The dark sphere behind the orange sphere is a view from inside the virus just below its surface. The smaller gray spheres in the background are negatively stained virus particles under electron microscopy.

Media contacts: Dr. Dennis Brown, professor and head of the Department of Biochemistry, N.C. State University, 919.515.5765 or dbrown@gmail.com; or Ricardo Vancini, graduate research assistant, rgvancin@ncsu.edu

A previously unknown virus discovered by North Carolina State University scientists may hold keys to managing another virus that causes a debilitating disease.

A virus that has been named Espirto Santo Virus (ESV) was discovered by Ricardo Vancini, a doctoral student working in the laboratory of Dr. Dennis Brown, head of the N.C. State Department of Biochemistry. The new virus has an unusual and as yet unexplained relationship with another virus, the virus that causes dengue fever.

If they can unravel this relationship, the scientists may find a way to control dengue fever.

Dengue fever, also known as breakbone fever, is a tropical disease caused by the dengue virus and spread by mosquitoes. The disease, which can be fatal, infects as many as 300 million people annually and is found in more than 100 countries around the world.

There are no vaccines for dengue fever, although a previous discovery by Brown and Dr. Raquel Hernandez, research associate professor at N.C. State, may lead to the development of a vaccine. Brown and Hernandez, who are husband and wife as well as research collaborators, discovered a way to alter viruses carried by insects so that they can be used to create vaccines for a range of diseases. The virus alteration technology was licensed to a North Carolina biotechnology startup company called Arbovax, which is using the technology to develop vaccines for several diseases, including dengue fever.

It is not yet clear how the Espirto Santo and dengue viruses interact, but Brown said the Espirto Santo virus appears to have a dampening antiviral effect on the dengue virus.

Vancini and Brown happened upon the Espirto Santo virus while studying the dengue virus. Brown said they obtained samples of a particular strain of dengue virus from the Fiocruz Institute in Rio de Janeiro, Brazil.

Picture of Dr. Dennis Brown and Ricardo Vancini

Dr. Dennis Brown, left, and Ricardo Vancini

“They (Fiocruz Institute) had a strain of dengue virus that grew exceptionally well, and we wanted it for the structural studies (of viruses) we do,” said Brown.

Vancini and Brown began working with the newly acquired virus, and when they looked at its structure with an electron microscope, it was quite different from other dengue viruses with which they had worked.

“The structure really didn’t look like typical dengue,” said Brown, “And we actually thought that we had found a new strain of dengue.”

Brown decided to have a mass spectrometry analysis done on the virus. Mass spectrometry identifies molecules by mass. The mass spectrometry analysis of what Brown and Vancini thought might be a new strain of dengue virus only deepened the mystery, because it indicated that the sample that was analyzed did not contain dengue or any other virus.

“We said, ‘Look, How can there be no virus in there? We’re looking at it,’” Brown recalled. “And what it was, there was no virus in there that was in any of the gene banks.”

In an effort to determine what they were actually working with, Vancini and Hernandez did a full characterization of the RNA that makes up the virus’ genetic identity.

Brown said this genetic characterization was sent to gene banks around the world, and it matched nothing on record. It was then that it dawned on the scientists that what they had on their hands was a new virus, previously unknown to science. Brown said Espirto Santo is a rare birnavirus, only a handful of such viruses are known to science, but it is more than that.

“I have never seen anything like it,” Brown said. “This virus seems to control the production of dengue. Dengue proteins are made inside the cells, but they don’t assemble into viruses. So there are two really interesting things that are happening. This virus, Espirto Santo, makes something that controls the production of dengue virus. At the same time, it needs the dengue virus in order to grow efficiently.”

The virus samples from Brazil did contain dengue virus, but they also contained Espirto Santo, and the presence of the Espirto Santo virus masked the presence of the dengue virus to the point it was almost imperceptible.

Now, Brown said, he, Herandez and Vancini, who plans to continue working in Brown’s lab as a post-doctoral researcher after earning his doctorate, are going to try to sort out the genetic factors involved in the relationship between the two viruses.

It appears, Brown said, that Espirto Santo, which was named for the area of Brazil where it was found, produces some type of antiviral agent that inhibits dengue virus particle production. Viruses reproduce by hijacking the reproductive mechanism of a cell and using the host cell’s reproductive machinery to produce virus particles. When dengue and Espirto Santo viruses infect a cell, the Espirto Santo virus produces virus particles, but the dengue virus is unable to reproduce.

Brown said he, Vancini and Hernandez plan to compare viral proteins produced in cells infected with dengue and Espirto Santo viruses alone with proteins produced in cells infected with the dengue-Espirto Santo combination to see if there are differences. And they’ll search for an antiviral substance as they try to tease apart the relationship between dengue and Espirto Santo.

Among the questions the scientists hope to answer is whether the dengue-Espirto Santo relationship exists only with one strain, or type, of dengue virus. Or does Espirto Santo inhibit viral particle production for other or, perhaps, all strains of dengue?

“There’s something there,” Brown said. “There’s something happening inside of that cell that’s preventing dengue virus from assembling. We need to find out what that is.”

Written by: Dave Caldwell, 919.513.3127 or dave_caldwell@ncsu.edu

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