Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

HIV targets active genes in cells

23.08.2002


HIV selectively inserts itself into active areas of a host cell’s genome, Salk Institute researchers have found for the first time. The fact that the virus hooks itself up to areas of the cell’s genome that are busy expressing themselves may help explain why HIV can replicate, or reproduce itself, so rapidly. The findings are being published as the cover article in the Friday, August 23, issue of the journal Cell.



"HIV seems to be targeting not just genes, but active genes," said Salk researcher Frederic Bushman, a specialist in infectious diseases who headed the research team. "That makes a lot of biological sense if the targeting has evolved to promote efficient expression of the viral genome once it integrates into the cell."

The findings may have implications for developing more effective gene therapies, said Bushman, Associate Professor in the Infectious Disease Laboratory. Gene therapy involves treating genetic disorders by using a mutated retrovirus to insert a new gene into a defective genome. Gene therapy could be made safer and more effective by knowing more about and taking advantage of a retrovirus’s targeting specificity, he said.


Retroviruses like HIV reproduce themselves by infecting a cell, making a DNA copy of the virus’s RNA genome, and integrating that DNA copy into a chromosome of the host. When the genome of the host is "read" to produce proteins and gene products, so is the genome of the virus-which reproduces itself. The question Bushman and his team sought to answer was, where in the human chromosome does the virus integrate itself?

The team took advantage of the recently published human genome sequence. The researchers infected human cells in tissue culture with the HIV virus, and then broke open the cells and sequenced pieces of DNA to find out where the viral DNA ended up. By matching DNA segments with the published human genome sequence, they found that that the viral DNA mostly ended up in areas of the chromosomes where there are human genes, rather than places in between.

The researchers then asked, "What is it about these genes? Are they active genes, or is it something else about being a gene that’s good?" Using another new technology, gene chips that help screen for products made by active genes, the researchers found that the genes that were targeted were disproportionately active ones.

In fact, Bushman said, the genes that are targeted are specifically ones that are turned on by infection with HIV itself. When the virus enters a cell, it triggers a response by the cell that includes making new proteins in response to the infection. So in essence, the HIV virus wields a double-edged sword, creating a weakness and then taking advantage of it.

Most HIV-infected cells die relatively quickly, within a day or two, Bushman said, so it’s to the virus’s advantage to be able to reproduce quickly. "Viruses that integrate into different points of the human genome inside a cell replicate with very different efficiencies," Bushman said. "There are bad places to be, where it’s hard to express your genome, and there are other places where you can express very efficiently." HIV, it appears, is extremely efficient.

HIV differs from other types of genomic pathogens, Bushman said, that have evolved to live with their host on a long-term basis. These may target relatively benign regions of the genome where they don’t hurt the host, and they reproduce because the cells continue to live, grow and divide, reproducing the pathogen as the cell itself reproduces.

"Not so with HIV," Bushman said. "HIV has aggressive targeting. That targeting is damaging to the host, but for an aggressive parasite in a cell that’s only going to live for a day or so, it makes a sensible evolutionary strategy."


Other members of the research team included Salk researchers Astrid Shröder (the paper’s lead author), Paul Shinn, Huaming Chen, Charles Berry, and Joseph Ecker.

The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit institution dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. Jonas Salk, M.D., founded the Institute in 1960 with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.

Kristin Bertell | EurekAlert!
Further information:
http://www.salk.edu/

More articles from Health and Medicine:

nachricht Finnish research group discovers a new immune system regulator
23.02.2018 | University of Turku

nachricht Minimising risks of transplants
22.02.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>