Nav: Home

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:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

The Immune System, 4th Edition
by Peter Parham (Author)

How the Immune System Works (The How it Works Series)
by Lauren M. Sompayrac (Author)

The Immune System Recovery Plan: A Doctor's 4-Step Program to Treat Autoimmune Disease
by Susan Blum (Author), Mark Hyman (Foreword), Michele Bender (Foreword)

Basic Immunology: Functions and Disorders of the Immune System
by Abul K. Abbas MBBS (Author), Andrew H. H. Lichtman MD PhD (Author), Shiv Pillai MBBS PhD (Author)

The Immune System, 3rd Edition
by Peter Parham (Author)

The Immune System: A Very Short Introduction (Very Short Introductions)
by Paul Klenerman (Author)

A Cure Within: Scientists Unleashing The Immune System to Kill Cancer
by Neil Canavan (Author)

How the Immune System Works, Includes Desktop Edition
by Lauren M. Sompayrac (Author)

Elegant Defense, An: The Extraordinary New Science of the Immune System: A Tale in Four Lives
by Matt Richtel (Author)

The Anti-Inflammatory Diet & Action Plans: 4-Week Meal Plans to Heal the Immune System and Restore Overall Health
by Dorothy Calimeris (Author), Sondi Bruner (Author)

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Approaching With Kindness
We often forget to say the words "thank you." But can those two words change how you — and those around you — look at the world? This hour, TED speakers on the power of gratitude and appreciation. Guests include author AJ Jacobs, author and former baseball player Mike Robbins, Dr. Laura Trice, Professor of Management Christine Porath, and former Danish politician Özlem Cekic.
Now Playing: Science for the People

#509 Anisogamy: The Beginning of Male and Female
This week we discuss how the sperm and egg came to be, and how a difference of reproductive interest has led to sexual conflict in bed bugs. We'll be speaking with Dr. Geoff Parker, an evolutionary biologist credited with developing a theory to explain the evolution of two sexes, about anisogamy, sexual reproduction through the fusion of two different gametes: the egg and the sperm. Then we'll speak with Dr. Roberto Pereira, research scientist in urban entomology at the University of Florida, about traumatic insemination in bed bugs.