How immune cells defend themselves against HIV

October 2, 2012

A team of scientists led by virologists Prof. Oliver T. Fackler and Prof. Oliver T. Keppler from Heidelberg University Hospital have decoded a mechanism used by the human immune system to protect itself from HIV viruses. A protein stops the replication of the virus in resting immune cells, referred to as T helper cells, by preventing the transcription of the viral genome into one that can be read by the cell. The ground-breaking results provide new insights into the molecular background of the immunodeficiency syndrome AIDS and could open up starting points for new treatments. The study has now been published – ahead of print online – in the international journal Nature Medicine.

Human immunodeficiency viruses attack different cells of the , most frequently, "T helper cells". These lymphocytes play a key role in , since they activate other immune cells upon contact with pathogens and set off subsequent immune responses. In the course of the HIV infection, they are continuously depleted until the immune system ultimately fails, culminating in AIDS with various infections.

In healthy people, the vast majority of T helper cells in the blood are in a resting state. They are not activated until they contact the pathogens against which they are specialized in defending. In the activated state, the cells are susceptible to HIV infection. "In contrast, resting T helper cells are immune to HIV: While the virus docks, and delivers its to the cell, the infection does not progress further. We have investigated why this is the case," explained Prof. Fackler, head of the working group at the Department of Infectious Diseases, Virology. Even if the T helper cells are activated later on, the virus does not replicate, because the genetic information of the virus is degraded during this period.

HIV genome cannot be transcribed into cell-compatible version

The team is headed by Prof. Fackler and Prof. Keppler, who moved from Heidelberg to the University Hospital in Frankfurt in April 2012 and now heads the Institute of Medical Virology there. The researchers discovered that the cellular protein SAMHD1 significantly contributes to protecting the resting immune cells. The protein is present in both resting and activated T helper cells and depletes nucleotides, the building blocks of genetic information. In the active phase the cells double their genetic information and divide, a process that depends on the continoues production of nucleotides. In the resting state, the cell does not require any nucleotides and stops their production, and SAMHD1 degrades the remaining nucleotides. "As a result, the HIV viruses most likely also lack the material they need to transcribe their genetic information into a version that can be used for the cell and to allow it to replicate," Fackler explained.

In the experiment, if SAMHD1 expression was silenced, resting T helper cells became susceptible to . The same was true for of a patient who is unable to produce SAMHD1 due to a hereditary condition. "This shows that HIV can only replicate in lymphocytes if the effect of the protective protein SAMHD1 is eliminated," Keppler said. In addition, the researchers discovered that this early protective measure must be followed by other barriers to HIV replication. Even without SAMHD1, no new viruses were released from resting T . Now that they have described the protective function of SAMHD1 and are able block it, the scientists can for the first time also investigate the downstream mechanisms. "We hope that we will be able to use these findings to develop new strategies in the fight against HIV," the virologist said.

Explore further: Researchers identify HIV-inhibiting mechanism

More information: Baldauf, H-M., et al. (2012). The deoxynucleoside triphosphate triphosphohydrolase SAMHD1 restricts HIV-1 infection in resting CD4+ T cells. Nature Medicine, published online ahead of print September 12, doi:10.1038/nm.2964

Related Stories

Researchers identify HIV-inhibiting mechanism

June 29, 2011
Researchers at Case Western Reserve University School of Medicine have discovered a long-sought cellular factor that works to inhibit HIV infection of myeloid cells, a subset of white blood cells that display antigens and ...

HIV study identifies key cellular defence mechanism

November 7, 2011
(Medical Xpress) -- Scientists have moved a step closer to understanding how one of our body’s own proteins helps stop the human immunodeficiency virus (HIV-1) in its tracks.

New memory for HIV patients

March 26, 2012
The hallmark loss of helper CD4+ T cells during human immunodeficiency virus (HIV) infection may be a red herring for therapeutics, according to a study published on March 26th in the Journal of Experimental Medicine.

Starve a virus, feed a cure? Findings show how some cells protect themselves against HIV

February 12, 2012
A protein that protects some of our immune cells from the most common and virulent form of HIV works by starving the virus of the molecular building blocks that it needs to replicate, according to research published online ...

Recommended for you

Scientists find where HIV 'hides' to evade detection by the immune system

October 19, 2017
In a decades-long game of hide and seek, scientists from Sydney's Westmead Institute for Medical Research have confirmed for the very first time the specific immune memory T-cells where infectious HIV 'hides' in the human ...

National roll-out of PrEP HIV prevention drug would be cost-effective

October 18, 2017
Providing pre-exposure prophylaxis (PrEP) medication to men who have sex with men who are at high risk of HIV infection (equivalent to less than 5% of men who have sex with men at any point in time) in England would be cost-effective, ...

Regulatory T cells harbor HIV/SIV virus during antiviral drug treatment

October 17, 2017
Scientists at Yerkes National Primate Research Center, Emory University have identified an additional part of the HIV reservoir, immune cells that survive and harbor the virus despite long-term treatment with antiviral drugs.

New research opens the door to 'functional cure' for HIV

October 17, 2017
In findings that open the door to a completely different approach to curing HIV infections, scientists from the Florida campus of The Scripps Research Institute (TSRI) have for the first time shown that a novel compound effectively ...

Researchers create molecule that could 'kick and kill' HIV

October 5, 2017
Current anti-AIDS drugs are highly effective at making HIV undetectable and allowing people with the virus to live longer, healthier lives. The treatments, a class of medications called antiretroviral therapy, also greatly ...

A sixth of new HIV patients in Europe 50 or older: study

September 27, 2017
People aged 50 and older comprise a growing percentage of HIV patients in Europe, accounting for one in six new cases in 2015, researchers said Wednesday.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.