Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Starve a virus, feed a cure?

13.02.2012
New findings show how some cells protect themselves against HIV

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 in Nature Immunology.

The finding comes from an international team of researchers including scientists from the University of Rochester Medical Center, NYU Langone Medical Center, several institutions in France – and a graduate student who is a political refugee from Africa and is now at work in a Rochester laboratory, intent on helping his people who have been devastated by the HIV epidemic.

While researchers hope the work will one day lead to a way to make anti-HIV drugs more effective by increasing their potency against the virus, they're also excited about its implications for our knowledge of other pathogens, such as herpes viruses, which use the same machinery within our cells that HIV does to replicate.

"The findings may explain why certain anti-HIV drugs used today are more effective under some circumstances and not others," said Baek Kim, Ph.D., professor of Microbiology and Immunology at the University of Rochester Medical Center and one of three corresponding authors of the paper. "It also provides new insights on how many other viruses that afflict people operate in the body."

The work centers on a protein known as SAMHD1, which is found in white blood cells known as macrophages and related cells known as dendritic cells. Last year scientists discovered that the molecule makes it difficult for HIV-1 to infect macrophages – cells that specialize in gobbling up and destroying invaders like viruses.

Now researchers have discovered that the molecule cuts off the supply line of the raw material that HIV needs to create DNA and replicate. That raw material, dNTP, comprises the building blocks of DNA, and without it, HIV can't recreate its DNA in our cells.

The team found that SAMHD1 destroys most of these building blocks, making it nearly impossible for HIV-1 to replicate itself where SAMHD1 resides – the macrophages. Instead, HIV-1 uses the macrophage as a safe haven, surviving in patients for years as it dodges the immune system as well as the drugs designed to kill it. It's thanks largely to its ability to hide out in the body that HIV is able to survive for decades and ultimately win out against the body's relentless immune assault.

The team also discovered how a protein in the other common type of HIV – HIV-2, which is found mainly in Africa – knocks out SAMHD1. They found that the protein Vpx destroys SAMHD1, clearing the way for HIV-2 to infect macrophages. While scientists have known that HIV-2 needs Vpx to infect macrophages, they hadn't known precisely why.

Interestingly, while one might think that a virus that is able to replicate itself in crucial cells like macrophages might be more dangerous than one that cannot, that's not the case with HIV. HIV-2 is actually less virulent than HIV-1.

"We don't know precisely how SAMHD1 and Vpx affect the virulence of HIV-1 and HIV-2, but it's something we're actively exploring," said Kim. "In this case, the ability of HIV-2 to replicate more quickly in macrophages does not help it become more virulent."

One possibility is that, like a starving man who becomes more and more desperate for food, the virus – when faced with a shortage of raw materials – puts its mutation gear into overdrive, creating more mutations in an effort to circumvent the pathway blocked by SAMHD1. Such constant mutations are one feature of HIV that makes it so challenging to treat patients.

"It makes sense that a mechanism like this is active in macrophages," said Kim. "Macrophages literally eat up dangerous organisms, and you don't want those organisms to have available the cellular machinery needed to replicate. And macrophages themselves don't need it, because they don't replicate. So macrophages have SAMHD1 to get rid of the raw material those organisms need to copy themselves. It's a great host defense.

"The work suggests new ways to target virus replication in macrophages, a critically important cell population that serves as a key reservoir of virus infection and a contributor to HIV-induced disease," added Kim.

At Rochester, Kim was joined in the research by graduate student Waaqo Daddacha, one of two first authors of the paper. A native of the Oromia region of Ethiopia, Daddacha came as a political refugee to the United States. He started out as a computer programmer, then decided to pursue HIV research as a way to help his homeland, where the rate of HIV is one of the highest in the world. As an undergraduate in Minnesota, he visited several laboratories around the nation that focus on HIV, eventually settling on the Kim lab, which he joined four years ago.

"Back home, many people are infected with HIV, and many people are dying because of it. I wanted to contribute to help solve the problem, and that's why I decided to pursue HIV research," said Daddacha, who still has family in Oromia. In Kim's lab he is focusing on understanding drug resistance among HIV patients and on finding ways to limit resistance to make the drugs more effective in patients.

Like Daddacha, Hichem Lahouassa of the National Health and Medical Research Institute is also co-first author of the paper. The other corresponding authors, in addition to Kim, are Nathaniel Landau, Ph.D., of NYU Langone Medical Center, and Florence Margottin-Goguet, Ph.D., of the National Health and Medical Research Institute in France.

The research was supported by the National Institutes of Health, the American Foundation for AIDS Research, the European Research Council, and several organizations in France.

Tom Rickey | EurekAlert!
Further information:
http://www.rochester.edu

More articles from Life Sciences:

nachricht Solving the efficiency of Gram-negative bacteria
22.03.2019 | Harvard University

nachricht Bacteria bide their time when antibiotics attack
22.03.2019 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>