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

Study shows how HIV is shielded from immune attack

July 10, 2018
Scientists from UNSW Sydney and the UK have discovered that the human immunodeficiency virus (HIV) hijacks a small molecule from the host cell to protect itself from being destroyed by the host's immune system.

Out-of-pocket costs put HIV prevention drug out of reach for many at risk

July 4, 2018
Public health officials are expanding efforts to get the HIV prevention pill into the hands of those at risk, in a nationwide effort to curb infections. But the officials are hitting roadblocks—the drug's price tag, which ...

New simulation tool predicts how well HIV-prophylaxis will work

June 14, 2018
A new mathematical simulation approach predicts the efficacy of pre- and post-exposure prophylaxis (PrEP) medications, which help prevent HIV infection. The framework, presented in PLOS Computational Biology by Sulav Duwal ...

Many at risk for HIV despite lifesaving pill

June 11, 2018
Multiple barriers may stop high-risk individuals from accessing an HIV drug that can reduce the subsequent risk of infection, according to a new University of Michigan study.

Active HIV in large white blood cells may drive cognitive impairment in infected mice

June 7, 2018
Macrophages, large white blood cells that engulf and destroy potential pathogens, harbor active viral reserves that appear to play a key role in impaired learning and memory in mice infected with a rodent version of HIV. ...

HIV vaccine elicits antibodies in animals that neutralize dozens of HIV strains

June 4, 2018
An experimental vaccine regimen based on the structure of a vulnerable site on HIV elicited antibodies in mice, guinea pigs and monkeys that neutralize dozens of HIV strains from around the world. The findings were reported ...

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.