“There’s a big hole in current therapies, in that all of them prevent new infection, but none attack the cells that are already infected and hidden from the immune response,” says Kathleen L. Collins, M.D., Ph.D., the study’s senior author and a U-M associate professor in both internal medicine and microbiology and immunology.
In people infected with HIV (human immunodeficiency virus), the virus that causes AIDS, there’s an unsolved problem with current anti-viral drugs. Though life-saving, they cannot root the virus out of the body. Infected cells are able to live on, undetected by the immune system, and provide the machinery for the virus to reproduce and spread.
“People have to be on the existing drugs, and when they’re not, the virus rebounds. If we can develop drugs that seek out and eradicate the remaining factories for the virus, then maybe we could eradicate the disease in that person,” Collins says.
Collins and her team show how Nef disables two key immune system players inside an infected cell. These are molecules called major histocompatability complex 1 proteins (MHC-1) that present HIV antigens to the immune system, and CD4, the cell-surface receptor that normally locks onto a virus and allows it to enter the cell.
Collins likens MHC-1 to motion detectors on a house, which send the first signal to a monitoring station if an invader breaks in.
“The immune system, especially the cytotoxic T lymphocytes, are like the monitors who get the signal that there’s a foreign invader inside the cell, and send out police cars,” she says. “The ‘police’ are toxic chemicals produced by T lymphocyte cells, which kill the cell that harbors the invader.”
By in effect pushing the MHC-I proteins into an infected cell’s “trash bin” so they fail to alert the T lymphocytes, Nef’s actions allow active virus to hide undetected and reproduce. Also, once a cell has been infected, Nef destroys CD4. The result is that this encourages new virus to spread to uninfected cells.
Nef’s activities are variable and complex. But the research team’s findings suggest that the many pathways involved may end in a final common step. That could make it possible to find a drug that could block several Nef functions.Implications:
In developing countries, the new drugs could have a huge impact, Collins says. Today, children born with HIV infection start taking the existing anti-HIV drugs at birth. It’s very hard to continue costly treatments for a lifetime. But if children could be cured within a few years, global HIV treatment efforts could spread their dollars further and be much more successful, she says.
Additional U-M authors are first author Malinda R. Schaefer, Ph.D.; Elizabeth R. Wonderlich, Jeremiah F. Roeth and Jolie A. Leonard.
Funding for the research came from the National Institutes of Health and U-M.
Citation: PLoS Pathogens, doi:10.1371/journal.ppat.1000131
Anne Rueter | Newswise Science News
Numbers count in the genetics of moles and melanomas
16.08.2019 | University of Queensland
Working out why plants get sick
16.08.2019 | Institut für Pflanzenbiochemie
Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.
Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...
Researchers at TU Graz are working together with European partners on new possibilities of measuring vehicle emissions.
Today, air pollution is one of the biggest challenges facing European cities. As part of the Horizon 2020 research project CARES (City Air Remote Emission...
Over the next three years, researchers from the Vrije Universiteit Brussel, University of Cambridge, École Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI-Paris) and Empa will be working together with the Dutch Polymer manufacturer SupraPolix on the next generation of robots: (soft) robots that ‘feel pain’ and heal themselves. The partners can count on 3 million Euro in support from the European Commission.
Soon robots will not only be found in factories and laboratories, but will be assisting us in our immediate environment. They will help us in the household, to...
Scientists at the University of Leeds have created a new form of gold which is just two atoms thick - the thinnest unsupported gold ever created.
The researchers measured the thickness of the gold to be 0.47 nanometres - that is one million times thinner than a human finger nail. The material is regarded...
An international team of scientists involving the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) in Hamburg has unraveled the light-induced electron-localization dynamics in transition metals at the attosecond timescale. The team investigated for the first time the many-body electron dynamics in transition metals before thermalization sets in. Their work has now appeared in Nature Physics.
The researchers from ETH Zurich (Switzerland), the MPSD (Germany), the Center for Computational Sciences of University of Tsukuba (Japan) and the Center for...
16.08.2019 | Event News
14.08.2019 | Event News
12.08.2019 | Event News
16.08.2019 | Life Sciences
16.08.2019 | Physics and Astronomy
16.08.2019 | Medical Engineering