Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Unveil New Monkey Model for HIV

03.03.2009
By altering just one gene in HIV-1, scientists have succeeded in infecting pig-tailed macaque monkeys with a human version of the virus that has until now been impossible to study directly in animals.

The new strain of HIV has already been used to demonstrate one method for preventing infection and, with a little tweaking, could be a valuable model for vetting vaccine candidates.

A team of researchers led by Paul Bieniasz and Theodora Hatziioannou at The Rockefeller University showed that two pig-tailed macaques, given a common antiretroviral treatment one week before and one week after being exposed to the newly engineered HIV, had no signs of infection.

“We’re not saying we can save the world with antiretroviral pills. But this model will allow us to start studying the best way to administer prophylaxis and do other experiments on preventing HIV-1 infection that could not be easily done on humans,” says Bieniasz, head of the Aaron Diamond AIDS Research Center Laboratory of Retrovirology at Rockefeller and a Howard Hughes Medical Institute investigator.

The findings, to be published Monday in the Proceedings of the National Academy of Sciences, show that the engineered virus injected into a pig-tailed macaque initially spreads almost as ferociously as it does in people and the virus remains detectable for at least six months. But it does not make the monkeys sick. Rather, it behaves as it is thought to behave in a group of HIV-positive people whose exceptional immune systems are generally able to keep the virus in check. These fortunate few are called long-term nonprogressors.

The animal model grew out of years of research into the molecular cloak-and-dagger fight between HIV and the cells of the host it infects. In particular, Bieniasz, who is also a scientist at the Aaron Diamond AIDS Research Center, Hatziioannou and colleagues have studied two groups of rapidly evolving genes, APOBEC3 and TRIM5, which produce unusual classes of defensive proteins with distinctive capabilities to fight retroviruses such as HIV. These genes, shared by humans and their simian forebears, have evolved mutations specific to each species’ unique history of retroviral battles.

In most simians, the APOBEC3 and TRIM5 proteins actually kill HIV on sight, making it impossible for researchers to study the virus in an animal model. Instead, they have studied HIV’s cousin, simian immunodeficiency virus (SIV), which causes an AIDS-like disease in certain monkey species. But SIV shares only about half of its amino acid sequence with HIV, making it a very imperfect substitute for testing anti-HIV drugs and vaccines. Several labs have engineered hybrids called SHIVs -- SIVs that contain pieces of HIV DNA -- but these have problematic differences, too.

Now, Bieniasz and Hatziioannou, working with Vineet KewalRamani and Jeffrey Lifson at the National Cancer Institute in Maryland, have developed a strain they call simian-tropic HIV-1 (stHIV-1), which shares about 95 percent of its genome with the human version. It differs only in the one HIV-1 gene that fails to deal with the pig-tailed macaques’ APOBEC3 defenses. (The scientists did not need to overcome their TRIM5 defenses because macaque TRIM5 proteins are extremely unusual and not effective against HIV). The new research marks a major advancement of experiments the Bieniasz and Hatziioannou team published in 2006 that showed that HIV engineered to hide from both the APOBEC3 and TRIM5 proteins in rhesus macaques could grow in their cells, at least in a test tube. But that strain’s growth was poor, and it failed to take root in the actual animals.

The new virus, stHIV-1, spreads almost as quickly after injection as HIV-1 initially does in humans and it persists for several months, after which it is controlled. Bieniasz and colleagues showed that that control is in part thanks to a specific class of immune system T cells that if blocked, allow a resurgence of the virus. The team demonstrated the use of the model by showing that a commonly used antiretroviral drug combination taken briefly before and after an injection of two million infectious units of stHIV-1 effectively protected the monkeys from the virus.

Though the work is an important advance, for stHIV-1 to be useful for testing vaccines, the scientists must modify the protein envelope that surrounds the virus so that it targets the same set of immune cells in monkeys as it does in humans. In addition, says Hatziioannou, an assistant professor at ADARC, they want the infection to run its full course and cause disease, to make it as faithful to HIV-1 as possible. “This model, even as is, should be useful for studying pre- or postexposure treatments,” she says. “But to have a really authentic model, we need to make it pathogenic, to make it hotter.”

This research was supported in part by the National Institute of Allergy and Infectious Diseases and the National Cancer Institute.

Brett Norman | Newswise Science News
Further information:
http://www.rockefeller.edu

More articles from Life Sciences:

nachricht Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>