Just in time for World AIDS day, the folks who discovered tetherin have a new paper out:
Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin.
Just a quick summary– Neil et al looked at the evolution of an HIV-1 protein, Vpu, and said ‘something is going on here.’ That ‘something’ turned out to be a previously unidentified component of your innate immune system. Rather than a physiological (skin) or cellular (macrophage) component, its kinda a chemical/protein component, like interferon gamma— tetherin.
What happens, is that when a virus infects a cell (any cell! innate immunity!), the cell will start producing tetherin. Tetherin then locks progeny viruses to the cell surface, where they are taken up and ‘digested’ by the infected cell, rather than being released to infect new cells.
HIV-1s Vpu protein interferes with tetherin, so HIV-1 viruses can bud off successfully.
So this labs next question was: is tetherin specific for retroviruses? For lentiviruses? How does this thing work?
Evidently, tetherin is a broad-spectrum antiviral. In this new paper, Jouvenet et al stripped a whole cadre of viruses down to their core structural protein, gag. They had to strip them down to their most basic components, because for all we know, some viral protein with an ‘unknown’ function interferes with tetherin. So when these stripped-down viruses were put into cells that do NOT produce tetherin, the ‘infected’ cells released lots of viral like particles (VLPs– empty shells of viruses).
When tetherin was added to the mix, VLP production stopped.
When HIV-1 Vpu was layered on top of all of this, VLP production resumed again.
This pattern emerged (at varying degrees) for:
- SIV from Macaques
- SIV from African Green Monkeys
- Equine Infectious Anemia VIrus
- Feline Immunodeficiency Virus
- Rouse Sarcoma Virus (alpharetrovirus)
- Mason Pfizer Monkey Virus (betaretrovirus)
- Human Endogenous Retrovirus-K
- Human T-Lymphotrophic Virus-1
- Prototypic Foamy Virus (spumavirus- a weird kind of retrovirus)
- Marburg Virus (related to Ebola)
Tetherin doesnt care which virus its tethering. It lassos all those bastards.
Vpu doesnt care which virus its liberating (it just happens to come from HIV-1)– it is focused on interfering with tetherin.
BUT all of those other viruses, when they arent stripped down to their structural proteins, can still infect cells (dir). They must encode their own way of evading tetherin (the SIVs envelope protein can!). Figuring out their respective tricks = New antiviral pharmaceuticals. I dunno about you all, but a drug that could stop Ebola in its tracks sounds pretty damn awesome.
And, what I would LOVE LOVE LOVE to see from this lab, is for them to take Vpu from the 1959 and 1960 HIV-1 isolates, and see how they compare to modern Vpu in their ability to interact with tetherin. *giddy clapping* They already used the HERV-K ‘phoenix’ virus– they know how to work with zombie viruses! DO IT guys!!