Research helps explain how antibody treatment led to lasting HIV-like virus remission

February 15, 2017
Diagrammatical representation of the molecular structure of HIV-1 protease complexed with the inhibitor indinavir. Credit: Public Domain

Scientists at the National Institutes of Health have found that the presence of the protein alpha-4 beta-7 integrin on the surface of HIV and its monkey equivalent—simian immunodeficiency virus, or SIV—may help explain why an antibody protected monkeys from SIV in previous experiments.

In October 2016, researchers reported that they had achieved sustained SIV remission in monkeys using a monkey antibody similar to the human drug vedolizumab, which is approved by the U.S. Food and Drug Administration for treating ulcerative colitis and Crohn's disease. The mechanism behind this observation has been unclear, but a new report presented today at the Conference on Retroviruses and Opportunistic Infections in Seattle provides clues.

Scientists have known that alpha-4 beta-7 integrin is a gut-homing receptor present at high levels on the immune-system cells that HIV and SIV preferentially infect. In the new study, scientists found that maturing HIV and SIV particles acquire alpha-4 beta-7 as they emerge from an infected cell, presenting researchers with a new target for HIV prevention and treatment and shedding light on how HIV disease develops.

"We expected the antibody to attack alpha-4 beta-7 on and reduce their movement to the gut, where HIV and SIV typically decimate the cells early in infection," said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, who co-authored the report as chief of the Laboratory of Immunoregulation (LIR).

"Instead, our team found that anti-alpha-4 beta-7 antibody binds not only to cells but also to HIV and SIV. This likely explains at least in part our previous observation that SIV-infected monkeys treated with antibody to alpha-4 beta-7 and antiretroviral therapy controlled the virus very effectively long after all treatment ended."

Studies conducted by Dr. Fauci and colleagues in his laboratory and at Emory University, Atlanta, between 2014 and 2016 showed that a laboratory-derived monkey antibody against alpha-4 beta-7 reduced the transmission of SIV to uninfected monkeys and induced sustained SIV remission in infected monkeys. Dr. Fauci's team undertook the current study to understand why.

HIV and SIV acquire their envelopes from the membranes of the cells from which they emerge, capturing some cellular proteins in the process. Led by Paolo Lusso, M.D., Ph.D., chief of the Viral Pathogenesis Section in the LIR, researchers discovered that HIV buds from membranes of immune cells precisely where alpha-4 beta-7 is concentrated and incorporates alpha-4 beta-7 into its envelope . In this way, the virus hijacks a cellular protein to sharpen its assault on the immune system.

Subsequently, Drs. Lusso, Fauci and colleagues conducted experiments to understand the function and prevalence of the alpha-4 beta-7 protein on the HIV envelope. They demonstrated in a mouse model that HIV bearing the protein homes to the gut. They also showed in cell culture that HIV infects alpha-4 beta-7-recognizing gut cells and their neighbors in a dramatically more efficient manner when the virus bears the protein than when it does not.

Finally, they demonstrated that blood samples taken from 33 HIV-infected people and 12 SIV-infected monkeys at multiple time points all had at least some virus bearing alpha-4 beta-7. The percentage of virus particles with the protein was greatest in blood samples taken during the early stage of infection, when the virus multiplies in the alpha-4 beta-7-rich immune cells of the gut.

Based on these findings, the researchers believe the protein is critical to the initial phase of infection, which has a major influence on the subsequent development of HIV disease.

The scientists' next step is to conduct a study to try to prove that the presence of alpha-4 beta-7 on SIV explains the protective effect of the anti-alpha-4 beta-7 antibody observed in the earlier monkey experiments.

Meanwhile, Dr. Fauci and other NIAID researchers are enrolling participants in a clinical trial to determine whether short-term treatment with vedolizumab in combination with antiretroviral therapy (ART) can generate sustained HIV remission in people living with HIV.

Explore further: Researchers achieve sustained viral remission in SIV infection

More information: Virion incorporation of alpha-4 beta-7 facilitates HIV-1 infection and intestinal homing. C. Guzzo, et al. Conference on Retroviruses and Opportunistic Infections, Feb. 15, 2017.

Related Stories

Researchers achieve sustained viral remission in SIV infection

October 13, 2016
Scientists have shown that they can achieve sustained control of infection by HIV's relative SIV (simian immunodeficiency virus) in rhesus macaques, by supplementing antiretroviral drugs with an antibody during and after ...

Immune-enhancing treatment may destabilize HIV reservoirs

July 21, 2016
Although antiretroviral therapy (ART) can reduce the amount of HIV in the blood to an undetectable level in most chronically infected people, it cannot eliminate reservoirs of HIV that persist in latently infected immune ...

Breast cancer study predicts better response to chemotherapy

December 15, 2016
It is known from previous research that the ER-beta estrogen receptor often has a protective effect. A new study from Lund University in Sweden has found that this effect is more pronounced in patients that undergo chemotherapy.

Breakthrough in diabetes research: Cells produce insulin upon artemisinin treatment

December 1, 2016
It promises to be a simple and elegant strategy to heal diabetes type 1: Replacing the destroyed beta-cells in the bodies of patients with newly-produced insulin-secreting cells. For years, researchers around the globe tried ...

Reprogramming cells to fight diabetes

February 22, 2013
For years researchers have been searching for a way to treat diabetics by reactivating their insulin-producing beta cells, with limited success. The "reprogramming" of related alpha cells into beta cells may one day offer ...

Recommended for you

New injectable antiretroviral treatment proved to be as effective as standard oral therapy

August 3, 2017
Intramuscularly administered antiretroviral therapy (ART) may be as effective for HIV treatment as current oral therapies. This is the main conclusion of a Phase II clinical trial carried out by 50 research centers around ...

Research finds home-based kit would increase HIV testing

July 31, 2017
Research led by William Robinson, PhD, Associate Research Professor of Behavioral & Community Health Sciences at LSU Health New Orleans School of Public Health, has found that 86% of heterosexuals who are at high risk for ...

Scientists divulge latest in HIV prevention

July 25, 2017
A far cry from the 1990s "ABC" campaign promoting abstinence and monogamy as HIV protection, scientists reported on new approaches Tuesday allowing people to have all the safe sex they want.

Girl's HIV infection seems under control without AIDS drugs

July 24, 2017
A South African girl born with the AIDS virus has kept her infection suppressed for more than eight years after stopping anti-HIV medicines—more evidence that early treatment can occasionally cause a long remission that, ...

Meds by monthly injection might revolutionize HIV care (Update)

July 24, 2017
Getting a shot of medication to control HIV every month or two instead of having to take pills every day could transform the way the virus is kept at bay.

Candidate AIDS vaccine passes early test

July 24, 2017
The three-decade-old quest for an AIDS vaccine received a shot of hope Monday when developers announced that a prototype triggered the immune system in an early phase of human trials.

0 comments

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.