Innate immune system can kill HIV when a viral gene is deactivated

March 28, 2013

Human cells have an intrinsic capacity to destroy HIV. However, the virus has evolved to contain a gene that blocks this ability. When this gene is removed from the virus, the innate human immune system destroys HIV by mutating it to the point where it can no longer survive.

This phenomenon has been shown in test tube , but now researchers at the University of North Carolina School of Medicine have demonstrated that the same phenomenon occurs in a humanized , suggesting a promising new target for tackling the virus, which has killed nearly 30 million people worldwide since it first appeared three decades ago.

A family of human proteins called APOBEC3 effectively restrict the growth of HIV and other viruses, but this action is fully counteracted by the viral infectivity factor gene (vif) in HIV. In the study, researchers intravenously infected humanized mice with HIV. They found that the most commonly transmitted strains of HIV are completely neutralized by APOBEC3 proteins when vif is removed from the virus.

"Without the vif gene, HIV can be completely destroyed by the body's own ," said J. Victor Garcia, PhD, professor of medicine at the UNC School of Medicine and senior author on the study. "These results suggest a new target for developing drugs fully capable of killing the virus."

Garcia and his colleagues pioneered the humanized mouse model used for these studies. The aptly named "BLT" mouse is created by introducing human bone marrow, liver and thymus tissues into animals without an immune system of their own. The mice have a fully functioning and can be infected with HIV in the same manner as humans. In previous research, Garcia and his team have effectively prevented intravenous, rectal, vaginal and oral in the mice with pre-exposure prophylaxis (PrEP).

For the current study, Garcia and his colleagues also infected BLT mice with another, highly harmful strain of the virus. The results show that this strain of HIV does continue to replicate, even without vif, but at a much slower rate and without harming the human immune system. Further, the researchers found that virus replication in this case was limited to one tissue—the thymus—in the entire body.

"These findings demonstrate a fundamental weakness in HIV," said John F. Krisko, PhD, lead author on the study. "If this weakness can be exploited, it might eventually lead to a cure for HIV/AIDS," Krisko said.

The study appears March 28 in the online journal PloS Pathogens.

Explore further: Preventing the spread of HIV/AIDS with humanized BLT mice

Related Stories

Preventing the spread of HIV/AIDS with humanized BLT mice

May 18, 2011

The more than 2.7 million new HIV infections recorded per year leave little doubt that the HIV/AIDS epidemic continues to spread globally. That's why there's the need for safe, inexpensive and effective drugs to successfully ...

Recommended for you

HIV vaccine design should adapt as HIV virus mutates

May 16, 2016

Human immunodeficiency virus is known to be a highly variable virus that adapts to a person's immune response during the lifetime infection, and a new study published in Nature Medicine shows that viral adaptation in HIV ...

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 ...

Researchers find alternative pathways to HIV antibodies

May 4, 2016

The immune system appears to hamper an investigational vaccine from inducing antibodies that protect against HIV infection, but there may be ways to overcome this impediment, according to research led by the Duke Human Vaccine ...

Fireflies light the way to female HIV transmission

April 27, 2016

Finding the vulnerable points where HIV enters the female reproductive tract is like searching for needles in a haystack. But Northwestern Medicine scientists have solved that challenge by creating a glowing map of the very ...

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.