“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
Less animal experiments on the horizon: Multi-organ chip awarded
19.10.2018 | Fraunhofer-Institut für Werkstoff- und Strahltechnik IWS
RUDN chemist tested a new nanocatalyst for obtaining hydrogen
18.10.2018 | RUDN University
Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz (Germany) together with scientists from Dresden, Leipzig, Sofia (Bulgaria) and Madrid (Spain) have now developed and characterized a novel, metal-organic material which displays electrical properties mimicking those of highly crystalline silicon. The material which can easily be fabricated at room temperature could serve as a replacement for expensive conventional inorganic materials used in optoelectronics.
Silicon, a so called semiconductor, is currently widely employed for the development of components such as solar cells, LEDs or computer chips. High purity...
Augsburg chemists present a new technology for compressing, storing and transporting highly volatile gases in porous frameworks/New prospects for gas-powered vehicles
Storage of highly volatile gases has always been a major technological challenge, not least for use in the automotive sector, for, for example, methane or...
When we put water in a freezer, water molecules crystallize and form ice. This change from one phase of matter to another is called a phase transition. While this transition, and countless others that occur in nature, typically takes place at the same fixed conditions, such as the freezing point, one can ask how it can be influenced in a controlled way.
We are all familiar with such control of the freezing transition, as it is an essential ingredient in the art of making a sorbet or a slushy. To make a cold...
Thin organic layers provide machines and equipment with new functions. They enable, for example, tiny energy recuperators. In future, these will be installed...
Das Zusammenspiel aus Struktur und Dynamik bestimmt die Funktion von Proteinen, den molekularen Werkzeugen der Zelle. Durch Fortschritte in der...
17.10.2018 | Event News
16.10.2018 | Event News
02.10.2018 | Event News
19.10.2018 | Earth Sciences
19.10.2018 | Life Sciences
19.10.2018 | Health and Medicine