Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Viral protein influences key cell-signaling pathway

27.04.2005


New research shows that a protein produced by a cancer-causing virus influences a key signaling pathway in the immune cells that the virus infects. This stimulates the cells to divide, helping the virus spread through the body.



The study, led by researchers at Ohio State University, examined the human T lymphotropic virus type 1 (HTLV-1) and a protein that it produces called p12. The research is published in the April issue of the journal AIDS Research and Human Retroviruses.

The study found that p12 increases the activity of an important gene in host cells. That gene controls production of a cell protein called p300. The p300 protein, in turn, controls a variety of other genes in many types of cells, including T lymphocytes, the cells that HTLV-1 infects.


The findings might help scientists better understand how HTLV-1 maintains its lifelong infection and how the normal immune cells that “remember” a vaccination or an infection can survive for years or even decades.

“The p300 protein is an important central regulator of gene activity in lymphocytes and many other kinds of cells,” says Michael Lairmore, professor and chair of veterinary biosciences and a member of the OSU Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. “We were surprised to see p300 show-up among the many genes affected by this viral protein.”

HTLV-1 infects an estimated 15 to 20 million people worldwide. In about five percent of them, the infection will lead to adult T cell leukemia or lymphoma (ATLL). ATLL is an aggressive disease characterized by a long latent period and the proliferation of T lymphocytes. The virus is spread by sexual activity, by contact with infected blood and by infected women to children through breast milk.

HTLV-1, like its cousin HIV, inserts its genetic information permanently into the DNA of a T lymphocyte and remains there for the life of the cell. HTLV-1 infection is also lifelong. A hallmark of HTLV-1 infection is the proliferation of T lymphocytes.

This sets HTLV-1 apart from HIV, Lairmore says. “Unlike HIV, which kills cells and destroys the immune system, HTLV-1 enhances the survival of T cells.”

But scientists don’t understand how it prolongs T-cell survival and causes their proliferation.

This study’s findings offer some clues. It is the latest in a series of studies led by Lairmore that examine how HTLV-1 affects T lymphocytes and causes cancer.

The p12 gene is called an “accessory gene” because the protein encoded by the gene seemed unnecessary since the virus could still reproduce, or replicate, in cells grown in the laboratory even when p12 was missing.

“But viruses do not keep genes unless they have a purpose,” Lairmore says. In an earlier study, Lairmore and his colleagues tried to infect an animal model with an HTLV-1 that lacked the p12 gene, and it stopped the virus from replicating almost entirely.

“That told us this gene was important,” he says.

Subsequent research led by Lairmore showed that the p12 protein travels to the network of membranes within the cell known as the rough endoplasmic reticulum (RER). Among other things, the RER helps regulate the amount of calcium in the cell. The investigators found that the p12 protein allows calcium to leak out of the RER, thereby causing calcium levels to rise elsewhere in the cell.

“Calcium is exquisitely regulated in cells,” Lairmore says. “When p12 affects that balance, it affects the activity of a variety of genes.”

The current study used a non-infectious form of HIV to transplant the HTLV-1 p12 gene into laboratory-grown T cells. The infected cells then produced a constant level of p12 protein. The researchers then used gene microarray technology to identify which cellular genes out of 33,000 become either more or less active due to the p12 protein.

The researchers found that p12 altered the activity of a variety of genes linked to chemical pathways that control cell signaling, proliferation and death. The p300 gene stood out as one showing increased activity.

Taken overall, the findings suggest that HTLV-1 p12 protein influences the genetic activity of infected T cells to stimulate their proliferation and promote efficient viral infection.

Funding from National Cancer Institute supported this research.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>