Researchers pave the way for a better understanding of HIV infection and AIDS

Sep 02, 2010

Dr. Eric A. Cohen, Director of the Human Retrovirology research unit at the Institut de recherches cliniques de Montreal (IRCM), and his team published yesterday, in the online open-access journal PLos Pathogens, the results of their most recent research on the role of the Vpr protein in HIV (human immunodeficiency virus) infection and AIDS (acquired immune deficiency syndrome).

"We previously identified that HIV, when infecting target cells, blocks cell division and induces cell death," says Dr. Cohen. "We then discovered that the Vpr protein was involved in this process."

HIV-1 encodes several proteins, including the R (Vpr), which plays an important role in the development of acquired immunodeficiency syndrome (AIDS). Vpr blocks normal cell division, a process believed to increase and to trigger immune cell death. The researchers recently showed that Vpr performs this activity by interacting with a complex (E3 ligase) involved in ubiquitination. Ubiquitination is characterized by the conjugation of a small protein called ubiquitin to various other proteins to regulate their degradation or activities. They also demonstrated that Vpr engages this protein complex to ubiquitinate a yet to be discovered host factor, whose degradation triggers the arrest of cell division.

"We understand the process, but we still don't know which cellular factor is targeted by Vpr to block cell division and where these events are occurring within the infected cell," explains Dr. Jean-Phillippe Belzile, a postdoctoral fellow in Dr. Cohen's research unit and first author of the article. "If we can identify this unknown host factor and determine its role in the cell cycle, it will undoubtedly have an impact on our understanding of HIV infection and the processes of immune cell death that characterize AIDS. We believe that the identification of this host factor could, in the long run, lead us to new potential therapeutic targets."

In this study, the researchers demonstrated that Vpr forms mobile structures called foci on the DNA of host cells. They also found that formation of these nuclear foci by Vpr is required to block cell division. They further showed that Vpr engages the E3 ligase within these mobile structures, and uses them to find a DNA-bound cellular protein and target it for degradation. This mechanism, in turn, results in the activation of a host cell response leading to a cell division block.

"Getting such insight into this process is very important, as it gives us and the scientific community a direction to focus our efforts to identify this unknown host factor, thereby contributing to a better understanding of the role of Vpr during and AIDS pathogenesis," adds Dr. Cohen.

Explore further: Animal study provides first evidence that gel can prevent multiple virus transmission in vagina/rectum

Provided by Institut de recherches cliniques de Montreal

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Scientific breakthrough at the IRCM to combat the HIV-1

Apr 08, 2010

The discovery by Dr. Éric A. Cohen's team at the Institut de recherches cliniques de Montréal, could potentially lead to the development of new strategies to combat the human immunodeficiency virus (HIV-1), ...

Mutant host cell protein sequesters critical HIV-1 element

Jan 15, 2009

Scientists have identified a new way to inhibit a molecule that is critical for HIV pathogenesis. The research, published by Cell Press in the January 16th issue of the journal Molecular Cell, presents a target for develo ...

Study: Cells have a natural defense against HIV

Mar 14, 2006

Scientists here have discovered a previously unknown mechanism that cells use to fight off the human immunodeficiency virus (HIV), the cause of AIDS. The findings indicate that two proteins that normally help repair cellular ...

How HIV hides itself

Apr 01, 2008

Researchers have discovered how Human Immunodeficiency Virus (HIV), which causes AIDS, can hide itself in our cells and dodge the attention of our normal defences, scientists heard today at the Society for General Microbiology’s ...

Recommended for you

HIV+ women respond well to HPV vaccine

Apr 16, 2014

HIV-positive women respond well to a vaccine against the human papillomavirus (HPV), even when their immune system is struggling, according to newly published results of an international clinical trial. The study's findings ...

User comments : 0

More news stories

Turning off depression in the brain

Scientists have traced vulnerability to depression-like behaviors in mice to out-of-balance electrical activity inside neurons of the brain's reward circuit and experimentally reversed it – but there's ...

Is Parkinson's an autoimmune disease?

The cause of neuronal death in Parkinson's disease is still unknown, but a new study proposes that neurons may be mistaken for foreign invaders and killed by the person's own immune system, similar to the ...