Nav: Home

How does HIV escape cellular booby traps?

April 04, 2018

Human immunodeficiency virus -- 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 human bodies 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 mouse model with a reconstituted human immune system, established through the transplantation of human blood-forming stem cells," 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 cells 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.
-end-
The paper "Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo" appeared 10 January 2018 in Cell Host & Microbe, with doi: 10.1016/j.chom.2017.12.009

Kyoto University is one of Japan and Asia's premier research institutions, founded in 1897 and responsible for producing numerous Nobel laureates and winners of other prestigious international prizes. A broad curriculum across the arts and sciences at both undergraduate and graduate levels is complemented by numerous research centers, as well as facilities and offices around Japan and the world. For more information please see: http://www.kyoto-u.ac.jp/en

Kyoto University

Related Hiv Articles:

Defective HIV proviruses reduce effective immune system response, interfere with HIV cure
A new study finds defective HIV proviruses, long thought to be harmless, produce viral proteins and distract the immune system from killing intact proviruses needed to reduce the HIV reservoir and cure HIV.
1 in 7 people living with HIV in the EU/EEA are not aware of their HIV status
Almost 30,000 newly diagnosed HIV infections were reported by the 31 European Union and European Economic Area (EU/EEA) countries in 2015, according to data published today by ECDC and the WHO Regional Office for Europe.
Smoking may shorten the lifespan of people living with HIV more than HIV itself
A new study led by researchers at Massachusetts General Hospital finds that cigarette smoking substantially reduces the lifespan of people living with HIV in the US, potentially even more than HIV itself.
For smokers with HIV, smoking may now be more harmful than HIV itself
HIV-positive individuals who smoke cigarettes may be more likely to die from smoking-related disease than the infection itself, according to a new study published in the Journal of Infectious Diseases.
Patients diagnosed late with HIV infection are more likely to transmit HIV to others
An estimated 1.2 million people live with HIV in the United States, with nearly 13 percent being unaware of their infection.
More Hiv News and Hiv Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...