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 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 the author. This design, 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 the author. "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 the author.
http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30545-0
Latest News
Connecting genetic risk for…
By newseditor
Posted 30 May
Tumor infiltration of immun…
By newseditor
Posted 28 May
New light-controlled 'off s…
By newseditor
Posted 28 May
Gene function during embryo…
By newseditor
Posted 28 May
Formation of 3D blood vesse…
By newseditor
Posted 27 May
Other Top Stories
Vessel co-option mediates resistance to anti-angiogenic therapy in…
Read more
A novel non-invasive imaging probe for fast and sensitive detection…
Read more
Anti-cancer effects found in natural compound derived from onions
Read more
Role of prolactin in triple negative breast cancer
Read more
Fat in feces points to early presence of colorectal cancer
Read more
Protocols
Accessible high-speed image…
By newseditor
Posted 30 May
SEMORE: SEgmentation and MO…
By newseditor
Posted 26 May
Spatially resolved lipidomi…
By newseditor
Posted 24 May
Efficient expansion and CRI…
By newseditor
Posted 21 May
Massively parallel in vivo…
By newseditor
Posted 20 May
Publications
I Am Curious About Cannabis…
By newseditor
Posted 30 May
Advanced microbiome therape…
By newseditor
Posted 29 May
Hippocampal astrocytes indu…
By newseditor
Posted 29 May
TNIK's emerging role in can…
By newseditor
Posted 29 May
Diabetes drugs activate neu…
By newseditor
Posted 29 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar