Insight on Protein That Blocks HIV
Replication May Help Battle Viral Reservoir
Welcome to another day in my life. Today is Thursday and I hope you are having a beary safe and great weekend. It is another busy week for Dab the AIDS Bear and me.
I read some very interesting information over the weekend that I would like to share with you in my blog today.
Researchers have discovered the regulation process for a protein that prevents HIV from making copies of itself in white blood cells. This finding provides insight that may lead to new ways to prevent HIV reservoirs from forming, or to eliminate those that persist in the face of antiretroviral treatment. Publishing their findings in the online edition of the journal Cell Host & Medicine, investigators from Albert Einstein College of Medicine of Yeshiva University studied a protein called SAMHD1, which prevents HIV from replicating in some immune cells but fails to do so in cells such as macrophages that make up the reservoir.
The investigators used mass spectrometry to deduce that SAMHD1 has two different configurations: one called phosphorylated and the other unphosphorylated. The unphosphorylated SAMHD1 proteins did not protect macrophages from HIV, while the phosphorylated proteins did.
“We are currently exploring ways to keep this protein unphosphorylated so that HIV reservoirs will never be formed,” Felipe Diaz-Griffero, PhD, assistant professor of microbiology and immunology at Einstein, said in a release.
Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered how the protein that blocks HIV-1 from multiplying in white blood cells is regulated. HIV-1 is the virus that causes AIDS, and the discovery could lead to novel approaches for addressing HIV-1 "in hiding" -- namely eliminating reservoirs of HIV-1 that persist in patients undergoing antiretroviral therapy.
The study was published today in the online edition of the journal Cell Host & Microbe.
Antiretroviral therapy can reduce blood levels of HIV-1 until they are undetectable. But despite drug therapy, reservoirs of HIV-1 can persist in several types of white cells, notably macrophages -- important immune cells that help clear pathogens and other potentially harmful substances from the body.
"If you stop antiretroviral therapy, the virus emerges from these reservoirs and returns to the general circulation in a matter of days, as if the patient had never been treated," said senior author Felipe Diaz-Griffero, Ph.D., assistant professor of microbiology & immunology at Einstein. "Now we know the protein that we need to control so we can prevent HIV-1 reservoirs from forming or eliminate them entirely."
Scientists have known that a protein called SAMHD1 prevents HIV-1 from replicating in certain immune cells. But until now, it was not understood why SAMHD1 fails to function in immune cells like macrophages that are vulnerable to HIV-1 infection.
Using mass spectrometry, a tool for determining molecular composition, Dr. Diaz-Griffero found that SAMHD1 can exist in two configurations known as phosphorylated and unphosphorylated. (Phosphorylation is an important cellular process in which phosphate groups attach to other molecules, thereby activating various signaling and regulatory mechanisms within the cell.) When SAMHD1 is phosphorylated -- the situation in immune cells that divide -- the cell is not protected from being infected with HIV-1. When the protein is not phosphorylated -- as occurs in the nondividing macrophages -- the cell is protected from HIV infection.
"We are currently exploring ways to keep this protein unphosphorylated so that HIV reservoirs will never be formed," said Dr. Diaz-Griffero.
The title of the paper is "The Retroviral Restriction ability of SAMHD1 is Regulated by Phosphorylation." Other Einstein contributors are Tommy E. White; Alberto Brandariz-Nuñez, Ph.D.; Jose Carlos Valle-Casuso, Ph.D.; and Marina Tuzova. Additional authors include Sarah Amie, Ph.D.; Laura Nguyen, Ph.D.; and Baek Kim, Ph.D., all at the University of Rochester School of Medicine and Dentistry, Rochester, NY.
The study was funded by a grant (AI087390) from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
Hope you have a beary safe and great start to your week.
Until we meet again; here's wishing you health, hope, happiness and just enough.
big bear hug,