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
Father's gut microbes affec…
By newseditor
Posted 08 May
A new brain circuit in mice…
By newseditor
Posted 08 May
Mechanism of choline entry…
By newseditor
Posted 07 May
Link between UTI and breast…
By newseditor
Posted 07 May
Sleep resets brain connections
By newseditor
Posted 07 May
Other Top Stories
Mating can cause epigenetic changes that last for 300 generations
Read more
Gene therapy to treat developmental disabilities
Read more
Neurotransmitter release impairment in schizophrenia with genetic m…
Read more
Prenatal editing in preclinical model to correct lysosomal storage…
Read more
Potential role of 'junk DNA' sequence in aging, cancer
Read more
Protocols
Single-cell adhesive profil…
By newseditor
Posted 07 May
Parasympathetic neurons der…
By newseditor
Posted 07 May
Non-invasive measurements o…
By newseditor
Posted 05 May
A validation strategy to as…
By newseditor
Posted 04 May
Generation of rat forebrain…
By newseditor
Posted 03 May
Publications
Paternal microbiome perturb…
By newseditor
Posted 08 May
Truncating NFKB1 variants c…
By newseditor
Posted 08 May
Synaptotagmin-11 facilitate…
By newseditor
Posted 08 May
Astrocytic Slc4a4 regulates…
By newseditor
Posted 08 May
Diabetic retinopathy is a c…
By newseditor
Posted 08 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