Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists find HIV-blocking protein in monkeys

26.02.2004


Organization of the HIV-1 Virion
Credit NIAID


Scientists at the Dana-Farber Cancer Institute have identified a protein that blocks HIV replication in monkey cells. Humans have a similar protein, although it is not as effective at stopping HIV, say the researchers whose work is published in this week’s issue of Nature. The team, headed by Joseph Sodroski, M.D., is supported by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).

"Identification of this HIV-blocking factor opens new avenues for intervening in the early stage of HIV infection, before the virus can gain a toehold," says NIAID Director Anthony S. Fauci, M.D. "The discovery also gives us critical insights about viral uncoating, a little understood step in the viral lifecycle. Basic discoveries like this provide the scientific springboard to future improvements in therapies for HIV disease."

"Over the years," notes Dr. Sodroski, "we’ve learned quite a bit about how HIV enters cells. More recently, we’ve developed a picture of the late stages of the viral lifecycle, as it leaves the cell. However, the steps between virus entry and conversion of the viral RNA into DNA have been a black box." A key preparatory step is the removal, or uncoating, of the protective shell surrounding HIV’s genetic material. This coat, called the capsid, must be removed before HIV can insert its genetic material into the host cell’s DNA and begin to make copies of itself. (See http://www.niaid.nih.gov/newsroom/graphics/hiv1.jpg for a simplified diagram of HIV, including the capsid.)



The discovery of this host protein helps pry open the black box of uncoating. Called TRIM5-alpha, it is the first found to specifically target HIV’s capsid. With the identification of a specific protein that powerfully inhibits viral uncoating, says Dr. Sodroski, comes the possibility of manipulating and enhancing its activity. For example, he notes, humans have a version of TRIM5-alpha. While it is not as efficient as the simian version, it does have some HIV-blocking ability. "Perhaps this protein could be induced to greater activity, thereby increasing the level of resistance to HIV infection," says Dr. Sodroski.

The discovery could also shorten the path to an AIDS vaccine by making improved animal models of HIV disease possible. Because monkeys are not susceptible to the human version of AIDS, results of vaccine trials conducted on them are not directly applicable to humans. Now with a better understanding of why HIV cannot successfully infect monkey cells, scientists have a defined target to manipulate and could use that information to develop animal models that more closely mimic HIV disease.

Matthew Stremlau, Ph.D., a member of Dr. Sodroski’s team and lead author on the new paper, searched the rhesus monkey genome and isolated a stretch of DNA that encodes the TRIM5-alpha protein. In a series of experiments using lab-grown cells that either possessed or lacked TRIM5-alpha, the scientists determined that TRIM5-alpha is both necessary and sufficient to block HIV replication. Although the precise mechanism of TRIM5-alpha’s activity is not fully determined, says Dr. Sodroski, it may be that the protein chops up HIV’s capsid and thwarts the orderly uncoating the virus must undergo before proceeding to replicate.

"This is a very exciting finding," says NIAID’s Nabila Wassef, Ph.D., a program officer in NIAID’s Division of AIDS. "TRIM5-alpha strikes at the heart of HIV, preventing it from becoming an established infection. As we know, HIV disease can be treated, but not cured. In part this is due to the ability of HIV to take up permanent residence in the body. If we could find a way to disable the virus before it has a chance to replicate, this problem of latent infection would be eliminated."

NIAID is a component of the National Institutes of Health (NIH), an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.


Reference: M Stremlau et al. The cytoplasmic body component TRIM5-á restricts HIV-1 infection in Old World monkeys. Nature 427:848-53 (2004).

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

Anne A. Oplinger | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Life Sciences:

nachricht First use of vasoprotective antibody in cardiogenic shock
17.05.2019 | Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.

nachricht A nerve cell serves as a “single” for studies
15.05.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Self-repairing batteries

UTokyo engineers develop a way to create high-capacity long-life batteries

Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...

Im Focus: Quantum Cloud Computing with Self-Check

With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.

Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...

Im Focus: Accelerating quantum technologies with materials processing at the atomic scale

'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.

However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...

Im Focus: A step towards probabilistic computing

Working group led by physicist Professor Ulrich Nowak at the University of Konstanz, in collaboration with a team of physicists from Johannes Gutenberg University Mainz, demonstrates how skyrmions can be used for the computer concepts of the future

When it comes to performing a calculation destined to arrive at an exact result, humans are hopelessly inferior to the computer. In other areas, humans are...

Im Focus: Recording embryonic development

Scientists develop a molecular recording tool that enables in vivo lineage tracing of embryonic cells

The beginning of new life starts with a fascinating process: A single cell gives rise to progenitor cells that eventually differentiate into the three germ...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

Discovering unusual structures from exception using big data and machine learning techniques

17.05.2019 | Materials Sciences

ALMA discovers aluminum around young star

17.05.2019 | Physics and Astronomy

A new iron-based superconductor stabilized by inter-block charger transfer

17.05.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>