AsianScientist (Apr. 12, 2018) – Scientists in Japan have discovered a protein that may have enabled the simian immunodeficiency virus (SIV) to be transmitted to humans. Their findings are published in Cell Host & Microbe.
The human immunodeficiency virus (HIV) is believed to have evolved from a 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 protein crucial for this protection, acts as a sticky pad on the surface of infected cells, preventing them from releasing nascent virus particles.
In an 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.
In this study, researchers led by Dr. Kei Sato and Dr. Yoshio Koyanagi of Kyoto University, Japan, set out to test whether the evolution of Vpu could have aided SIV in making the leap to humans.
“We used an immunodeficient mouse model with a reconstituted human immune system, established through the transplantation of human blood-forming stem cells,” Koyanagi explained.
This design allowed for both SIV and HIV infection to be studied in the mice. By engineering 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,” said Sato. “The Vpu variant responsible for downregulating tetherin was the most important property of Vpu for HIV.”
The researchers also found that returning tetherin to normal levels could suppress virus replication. Interestingly, SIV could not effectively infect human blood cells in the mouse model. However, when the Vpu of SIV was endowed with properties resembling that of HIV, 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: humans,” Sato concluded.
The article can be found at: Yamada et al. (2018) Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo.
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Source: Kyoto University; Photo: Shutterstock.
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