EBOV VP24, pieni matrix proteiini on interferoniantagonisti

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002550
VP24 pystyy vaimentamaan interferonijärjestelmää ainakin ahdella eri tavalla ( tästä tarkkemmin jo mainittu.
 Se estää isäntäsolun PY-STAT1 tekijän pääsyn  tumaan hälyttämään intereronijärjestelmän aktivoitumista kaappaamalla sen tumasignaalin alfa-karyoferiinin.( isäntäsoluproteiinin). Lisäksi  VP24  voi vaikuttaa suoraan STAT1 molekyyliin.

Vertaa VP35 ja VP24 interferoniantagonistisuuden  eri aluita: . VP35 toimii  upstream ja  VP24 downstream  puolla   IFNalfa/beta- signalointi järjestelmää  tuhotessaan: VP35 ei salli edes  IFN alfa/betaa  muodostua, VP24 ei salli niiden  vaikuttaa .ja herättää niitä yli sataa antivirusgeeniä.

--- the pathogenic ebolaviruses, early suppression of host interferon (IFN) production and signaling plays a decisive factor in disease outcome [4], [5]. Two proteins of the ebolaviruses are used in this strike. The protein VP35 blocks production of IFN-α/β [6] by binding dsRNA, a key hallmark of viral infection, and shielding it from recognition by host immune sensors such as RIG-I and MDA-5 [7], [8]. By contrast, the protein VP24 inhibits signaling downstream of both IFN-α/β and IFN-γ by sequestering karyopherin α proteins (α1, α5 and α6) [9]. Binding to these proteins prevents them from shuttling otherwise activated, phosphorylated STAT1 to the nucleus [9]–[11].
STAT1 belongs to the STAT family of transcription factors, is a key mediator of the IFN response pathway [12]–[14] and plays an essential role in the immune response to viruses [15]–[17]. STAT1 predominately exists in an unphosphorylated form (U-STAT1). Numerous immune factors like type I and type II interferon [14], [18], [19], interleukins like IL-6 and IL-10 [20]–[23], growth factors [20], [24]–[26], angiotensin [27], and TNFα [28] cause STAT1 to be phosphorylated (P-STAT1) by the Janus family kinases (JAKs). Upon phosphorylation, P-STAT1 either dimerizes or forms a complex with IFN α/β-stimulated gene factor 3 (ISGF3) [18], [29], [30], and is subsequently transported to the nucleus via karyopherin α proteins where it regulates genes involved in the immune response [31]–[33].


Minkälainen molekyyli on VP24?
Virologinen kuvasu pyramidisesta hahmosta.  http://jvi.asm.org/content/88/10/5859.figures-only


 Miten se eroaa  patogeenisen ebolaviruksen ( EBOV) ja nonpatogeenisen ebolaviruksen   (RESTV) kesken?

Ebolavirusprotein VP24 prevents transcription of STAT1, thus hindering IFN mediated broad antiviral immune response

Here’s how Ebola affects the immune system
Researchers showed the Ebola virus protein called VP24 is responsible for actually disrupting the cell’s innate or natural immune response, making it extremely deadly. VP24 directly prevents the transcription factor STAT1, which carries interferon’s antiviral message, from entering the nucleus and initiating an immune response. According to Chris Basler of the Icahn School of Medicine at Mount Sinai, once we figure out how VP24 promotes this disruption new ways to defeat the virus could be explored.
http://jvi.asm.org/content/80/11/5168.abstract