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 down-regulating 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.
The paper "Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo" appeared Jan. 10, 2018 in Cell Host & Microbe, with doi: 10.1016/j.chom.2017.12.009
Source: Kyoto University
Show, Tell, Teach: Elevating EVS Training Through Cognitive Science and Performance Coaching
April 25th 2025Training EVS workers for hygiene excellence demands more than manuals—it requires active engagement, motor skills coaching, and teach-back techniques to reduce HAIs and improve patient outcomes.
The Rise of Disposable Products in Health Care Cleaning and Linens
April 25th 2025Health care-associated infections are driving a shift toward disposable microfiber cloths, mop pads, and curtains—offering infection prevention, regulatory compliance, and operational efficiency in one-time-use solutions.
Phage Therapy’s Future: Tackling Antimicrobial Resistance With Precision Viruses
April 24th 2025Bacteriophage therapy presents a promising alternative to antibiotics, especially as antimicrobial resistance continues to increase. Dr. Ran Nir-Paz discusses its potential, challenges, and future applications in this technology.