Retrovirus replication process different than thought

Jul 15, 2010

How a retrovirus, like HIV, reproduces and assembles new viruses is different than previously thought, according to Penn State College of Medicine researchers. Understanding the steps a virus takes for assembly could allow development of a way to prevent the spread of retroviral diseases.

The team studied a chicken virus called Rous sarcoma virus that causes cancer in chickens and is similar to HIV.

"The question is, how do retroviruses build new ?" asked Leslie Parent, M.D., Ph.D., professor of , department of medicine. "There are no inhibitors of HIV assembly in clinical use. If we can determine how retroviruses are built, we can help stop the spread of infection through the creation of new drugs."

The start of the replication process is the production by the of a protein called Gag. Prior to this study, it was thought the building process happened outside the nucleus in the cyctoplasm -- the material that fills the cell -- and then Gag protein was sent to the plasma membrane -- the outer boundary of the cell. The researchers discovered, however, that Rous sarcoma virus takes a detour through the before going to the .

The Gag protein has a signal, which tells a receptor to take it into the nucleus. Once in the nucleus, Gag binds to the viral RNA. The viral RNA alters the structure of the protein, changing the way it folds. This new configuration triggers a different signal that allows the Gag to move out of the nucleus.

"There's a sequence of events that has to happen in a very specific order," Parent explained. "The Gag protein has to find its own RNA, build a virus particle around it, and then release it from the cell." Finding the is the first committed step in the assembly process. By focusing on regulatory processes in assembly, researchers are looking for key events that, if disrupted, could stop the virus from spreading.

"We want to understand the smallest building blocks of the virus particle," Parent said. "If we interfere with the first step, the will never be released from the cell. Cells are complex, so we use the key elements in a test tube to figure out how Gag and the RNA interact."

This study built on a 2002 paper, which proposed a model for the Gag protein's entry into the nucleus. The researchers reported in the Proceedings of the National Academy of Sciences that Gag does travel in the nucleus. Further study will examine how the Gag complex travels from the nucleus to the .

Explore further: In between red light and blue light: Researchers discover new functionality of molecular light switches

Related Stories

New electron microscopy images reveal the assembly of HIV

Jun 23, 2009

Scientists at the European Molecular Biology Laboratory (EMBL) and the University Clinic Heidelberg, Germany, have produced a three-dimensional reconstruction of HIV (Human Immunodeficiency Virus), which shows ...

How sneaky HIV escapes cells

Jun 05, 2007

Like hobos on a train, HIV, the virus that causes AIDS, uses a pre-existing transport system to leave one infected cell and infect new ones, Hopkins scientists have discovered. Their findings, published in the June issue ...

HIV uses autophagy for its own means

Jul 27, 2009

Not satisfied with simply thwarting its host's defensive maneuvers, HIV actually twists one to its advantage, based on new findings from Kyei et al. in the July 27, 2009 issue of the Journal of Cell Biology. Vojo D ...

Recommended for you

Structure of an iron-transport protein revealed

4 hours ago

For the first time, the three dimensional structure of the protein that is essential for iron import into cells, has been elucidated. Biochemists of the University of Zurich have paved the way towards a better ...

Over-organizing repair cells set the stage for fibrosis

5 hours ago

The excessive activity of repair cells in the early stages of tissue recovery sets the stage for fibrosis by priming the activation of an important growth factor, according to a study in The Journal of Ce ...

Cell architecture: Finding common ground

Oct 16, 2014

When it comes to cellular architecture, function follows form. Plant cells contain a dynamic cytoskeleton which is responsible for directing cell growth, development, movement, and division. So over time, changes in the cytoskeleton ...

User comments : 0