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

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.

Related Stories

Preventing the spread of HIV/AIDS with humanized BLT mice

date 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 ...

PrEP treatment prevented HIV transmission in humanized mice

date Jan 21, 2010

Systemic pre-exposure administration of antiretroviral drugs provides protection against intravenous and rectal transmission of HIV in mice with human immune systems, according to a new study published January 21, 2010 in ...

Recommended for you

Indiana HIV outbreak, hepatitis C epidemic sparks US alert

date Apr 24, 2015

Federal health officials helping to contain an HIV outbreak in Indiana state issued an alert to health departments across the U.S. on Friday, urging them to take steps to identify and track HIV and hepatitis C cases in an ...

Why are HIV survival rates lower in the Deep South than the rest of the US?

date Apr 22, 2015

The Deep South region has become the epicenter of the US HIV epidemic. Despite having only 28% of the total US population, nine states in the Deep South account for nearly 40% of national HIV diagnoses. This region has the highest HIV diagnosis rates and the highest number of people living with HIV of any ...

A bad buzz: Men with HIV need fewer drinks to feel effects

date Apr 20, 2015

Researchers at Yale and the VA Pittsburgh Healthcare System compared the number of drinks that men with HIV infection, versus those without it, needed to get a buzz. They found that HIV-infected men were more sensitive to ...

Research informs HIV treatment policy for inmates

date Apr 16, 2015

A national, five-year study of care for inmates with HIV brought strangers together, produced policy change in the Delaware Department of Corrections and documented the importance of good communication and ...

User 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.