How does HIV escape cellular booby traps?

April 5, 2018, Kyoto University
Utilizing the humanized mouse model the team found that HIV-1 Vpu inhibiting tetherin at the beginning of infection (right) is key for successful viral infection. SIVcpz Vpu does not have this function (left) adapting and evolving in order to jump to humans. Credit: Kyoto University / Sato Lab

HIV is believed to have evolved from a simian immunodeficiency virus, or SIV, that originated in chimpanzees. How SIV made the species jump has remained a mystery, since humans possess a defense mechanism that should prevent such infections. Tetherin, a crucial protein for this protection, acts as a sticky pad on the surface of infected cells, preventing them from releasing nascent virus particles.

In this evolutionary battle, viruses have developed their own arsenal of proteins as a countermeasure. For example, Vpu, an HIV accessory protein that targets tetherin, allows HIV to escape and spread. An international team led by Kei Sato and Yoshio Koyanagi of Kyoto University set out to test whether the evolution of Vpu could have aided SIV in making the leap to humans. Their study, published in the journal Cell Host and Microbe, helps explain how HIV came into our world.

"We used an immunodeficient with a reconstituted human immune system, established through the transplantation of human ," explains Koyanagi. This design, he adds, allowed for both SIV and HIV infection to be studied in the mice.

Using reverse genetics to engineer several HIV strains with different Vpu mutants, the team investigated which Vpu function was key for successful virus infection.

"Vpu can inhibit immune signaling pathways in the cell and degrade tetherin," states Sato. "The Vpu variant responsible for downregulating tetherin was the most important property of Vpu for HIV."

They also found that returning tetherin to normal levels could suppress virus replication, suggesting that a minimal number of tetherin molecules can combat HIV.

Interestingly, SIV could not effectively infect human blood in the mouse model. But when SIV Vpu was endowed with properties resembling HIV Vpu—namely, anti-tetherin activity blood cell infection did occur.

"From an evolutionary standpoint, our study suggests that a gain-of-function ability in Vpu to overcome human tetherin allowed SIV to infect a new host: us," concludes Sato.

Explore further: Study of patients infected with both HIV and hepatitis shows how the drug interferon works to suppress virus

More information: Eri Yamada et al, Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo, Cell Host & Microbe (2018). DOI: 10.1016/j.chom.2017.12.009

Related Stories

Study of patients infected with both HIV and hepatitis shows how the drug interferon works to suppress virus

February 29, 2012
A drug once taken by people with HIV/AIDS but long ago shelved after newer, modern antiretroviral therapies became available has now shed light on how the human body uses its natural immunity to fight the virus—work ...

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 ...

Recommended for you

Eliminating the latent reservoir of HIV

December 7, 2018
A new study suggests that a genetic switch that causes latent HIV inside cells to begin to replicate can be manipulated to completely eradicate the virus from the human body. Cells harboring latent HIV are "invisible" to ...

New research highlights why HIV-infected patients suffer higher rates of cancer

December 5, 2018
AIDS patients suffer higher rates of cancer because they have fewer T-cells in their bodies to fight disease. But new research examines why HIV-infected patients have higher rates of cancer—among the leading causes of death ...

Focus on resistance to HIV offers insight into how to fight the virus

November 30, 2018
Of the 40 million people around the world infected with HIV, less than one per cent have immune systems strong enough to suppress the virus for extended periods of time. These special immune systems are known as "elite controllers." ...

Patients with rare natural ability to suppress HIV shed light on potential functional cure

November 27, 2018
Researchers at Johns Hopkins have identified two patients with HIV whose immune cells behave differently than others with the virus and actually appear to help control viral load even years after infection. Moreover, both ...

Scientists unveil promising new HIV vaccine strategy

November 26, 2018
A new candidate HIV vaccine from Scripps Research surmounts technical hurdles that stymied previous vaccine efforts, and stimulates a powerful anti-HIV antibody response in animal tests.

Influential U.S. panel backs PrEP HIV-prevention pills

November 20, 2018
(HealthDay)—For the first time, a highly influential panel of experts says doctors should offer a daily pill to prevent HIV transmission to people who are at high risk for infection with the AIDS-causing virus.

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.