Researchers uncover clues about how HIV virus mutates

June 1, 2017, Fred Hutchinson Cancer Research Center
HIV infecting a human cell. Credit: NIH

A new study published in Cell Host & Microbe led by researchers at Fred Hutchinson Cancer Research Center completely maps all mutations that help the HIV virus evolve away from a single broadly neutralizing antibody, known as PGT151. Broadly neutralizing antibodies are immune molecules that bind to viruses and can block them from spreading in the body.

To get at the question of how broadly neutralizing antibodies affect HIV mutation, evolutionary biologist Dr. Jesse Bloom teamed up with HIV researcher Dr. Julie Overbaugh and doctoral student Adam Dingens. The mutations they uncovered are a mix of those that had been discovered in previous studies as well as some newly discovered sites.

Using a library of envelope, or Env, mutants made in a strain of HIV directly isolated from an infected child, the team infected T cells in the lab in the presence of PGT151. As the protein that covers HIV's surface, Env is the primary part of the virus that the immune system can see and act on. HIV is a particularly notorious foe for both the natural immune system and for immune reactions spurred by vaccines in part because Env mutates so rapidly, slipping away from immune recognition before the body can effectively rid itself of the infection.

The researchers then sequenced the mutant viral strains that were able to infect cells in a petri dish in the presence of this antibody to see which mutations allowed HIV to escape PGT151.

This is important, Bloom said, for researchers to better understand the evolutionary paths HIV could take to escape a broadly neutralizing antibody—and, ultimately, to understand how to head off those paths through smarter design.

Studies like this also yield, indirectly, an inferred map of where a given antibody binds to a given virus—and the method is simpler than 3-D crystallography, the gold standard in the field of understanding how two proteins interact. The that allow HIV to slip through the antibody binding and infect cells in the lab are by their nature going to be in sites important for how the viral protein connects with the antibody.

All of this falls under the rubric of better understanding HIV's biology to continue building a foundation for better , Bloom said. We have many working vaccines against other viruses that researchers don't fully understand, he said, but for really tricky viruses like HIV, "we're going to need to be more rational about how we make vaccines."

"If we can understand where the antibodies bind, we can engineer vaccines that elicit more of those types of antibodies," Bloom said. "And when we find really good , we can understand what parts of the are sites of vulnerability."

Explore further: Antibody combination puts HIV on the ropes

Related Stories

Antibody combination puts HIV on the ropes

January 25, 2017
Without antiretroviral drug treatment, the majority of people infected with HIV ultimately develop AIDS, as the virus changes and evolves beyond the body's ability to control it. But a small group of infected individuals—called ...

Researchers map pathways to protective antibodies for an HIV vaccine

March 15, 2017
A Duke Health-led research team has described both the pathway of HIV protective antibody development and a synthetic HIV outer envelope mimic that has the potential to induce the antibodies with vaccination.

Hepatitis C mutations 'outrun' immune systems, lab study shows

March 15, 2017
Unlike its viral cousins hepatitis A and B, hepatitis C virus (HCV) has eluded the development of a vaccine and infected more than 170 million people worldwide. Now, researchers at Johns Hopkins Medicine report that a novel ...

Study models how the immune system might evolve to conquer HIV

July 21, 2016
It has remained frustratingly difficult to develop a vaccine for HIV/AIDS, in part because the virus, once in our bodies, rapidly reproduces and evolves to escape being killed by the immune system.

Study discovers new HIV vaccine target

May 12, 2016
A team led by scientists at the National Institutes of Health (NIH) has reported a research trifecta. They discovered a new vulnerable site on HIV for a vaccine to target, a broadly neutralizing antibody that binds to that ...

Antibody discovery could help create improved flu vaccines

September 13, 2016
Dana-Farber Cancer Institute investigators report they have discovered a type of immune antibody that can rapidly evolve to neutralize a wide array of influenza virus strains - including those the body hasn't yet encountered.

Recommended for you

Researchers find new way to defeat HIV latency

March 8, 2018
HIV, the virus that causes AIDS, has a secret life. Though anti-retroviral therapy can reduce its numbers, the virus can hide and avoid both treatments and the body's immune response.

Broadly neutralizing antibody treatment may target viral reservoir in monkeys

March 5, 2018
After receiving a course of antiretroviral therapy for their HIV-like infection, approximately half of a group of monkeys infused with a broadly neutralizing antibody to HIV combined with an immune stimulatory compound suppressed ...

HIV begins to yield secrets of how it hides in cells

March 2, 2018
UC San Francisco scientists have uncovered new mechanisms by which HIV hides in infected cells, resting in a latent state that evades the body's immune system and prevents antiviral drugs from flushing it out.

HIV exports viral protein in cellular packages

February 15, 2018
HIV may be able to affect cells it can't directly infect by packaging a key protein within the host's cellular mail and sending it out into the body, according to a new study out of a University of North Carolina Lineberger ...

Can gene therapy be harnessed to fight the AIDS virus?

February 13, 2018
For more than a decade, the strongest AIDS drugs could not fully control Matt Chappell's HIV infection. Now his body controls it by itself, and researchers are trying to perfect the gene editing that made this possible.

Big data methods applied to the fitness landscape of the HIV envelope protein

February 7, 2018
Despite significant advances in medicine, there is still no effective vaccine for the human immunodeficiency virus (HIV), although recent hope has emerged through the discovery of antibodies capable of neutralizing diverse ...


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.