Defective HIV proviruses reduce effective immune system response, interfere with HIV cure

April 19, 2017

WASHINGTON (April 19, 2017) -- Defective HIV proviruses, long thought to be harmless, produce viral proteins and distract the immune system from killing intact proviruses needed to reduce the HIV reservoir and cure HIV. Researchers at the George Washington University (GW) and Johns Hopkins University publish their findings in Cell Host & Microbe.

Current HIV cure research focuses on eliminating intact proviruses in infected patients. However, the ratio of intact and defective proviruses is about one to 1,000, creating a "needle in a haystack problem," according to Brad Jones, Ph.D., co-first author of the paper and assistant professor of microbiology, immunology, and tropical medicine at the GW School of Medicine and Health Sciences.

"For a long time, most of the field has thought that we don't have to worry about defective proviruses, because they could never restart infection," said Jones. "Our research shows that these defective proviruses can actually produce some viral proteins. While they can't produce an infection, they do harm by acting as decoy viruses and distracting the immune system."

Researchers in the field have been frustrated with defective proviruses because they interfere with measurement -- most assays used to measure HIV will measure both the intact and defective proviruses. However, this research details their role as much more active. By producing viral proteins, the immune system expends resources on defective proviruses, rather than intact viruses.

"It's a much bigger issue than we expected," said Jones. "In a way, this is a setback, but every time we learn what the obstacles are, we are moving forward. Perhaps we didn't quite know how far we had to go at the beginning."

Further research may lead to different courses of treatment for HIV patients. If one therapy kills defective proviruses, it may still be considered of benefit, even if it doesn't kill all intact proviruses. Also, efforts to kill defective proviruses may lead to much stronger immune responses to clear both defective and intact proviruses.
-end-
This research was supported in part by the BELIEVE grant - a multimillion-dollar HIV/AIDS cure research grant awarded to GW as part of the second iteration of the Martin Delaney Collaboratory at the National Institutes for Health. amfAR generationCURE also had a significant role in funding this research. In addition, this research was supported by the Johns Hopkins University Center for AIDS Research and the District of Columbia Center for AIDS Research.

"Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape," published in Cell Host & Microbe, is available at http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30118-X.

Media: To interview Dr. Jones, please contact Lisa Anderson at lisama2@gwu.edu or 202-994-3121.

About the GW School of Medicine and Health Sciences

Founded in 1824, the GW School of Medicine and Health Sciences (SMHS) was the first medical school in the nation's capital and is the 11th oldest in the country. Working together in our nation's capital, with integrity and resolve, the GW SMHS is committed to improving the health and well-being of our local, national and global communities. smhs.gwu.edu

George Washington University

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.