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Infection of XC Cells by MLVs Is Endosome-Dependent but Acidific-Independent

Jemal

Senior Member
Messages
1,031
This is a study from Japan that talks about XMRV/MLV's. It was published 12 oct.
It's all gibberish to me... I can understand some of the words, but that's about it. And it's in English, not even in Japanese :D
Does anyone understand what they are talking about here?

Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells.

In this study, we investigated whether the Poly-, Xeno-, and XMRV-MLV vector infections occur through acidic endosomes and whether these infections require cathepsin protease activity. We also examined the pH-independent mechanism of MLV infections in XC cells. We found that the Poly- Xeno-, and XMRV-MLV vector infections occur through acidic endosomes and require cathepsin proteases similar to the Eco-MLV, Ampho-MLV, and Ebola virus infections. The endosome acidification inhibitors attenuated all these viral infections in NIH3T3 and TE671 cells, but had no effect in XC cells, as previously shown [11]. The endosome acidification inhibitors attenuated cathepsin protease activities in TE671 cells, but had no effect in XC cells, indicating that cathepsin proteases are activated without endosome acidification in XC cells. Suppression of endocytosis by a dynamin GTPase inhibitor, dynasore, or by siRNA-mediated knockdown of dynamin 2 expression attenuated the MLV infections in all cells examined (including XC cells), showing that these infections occur through endosomes even in XC cells. These results show that cathepsin proteases are activated in the absence of endosome acidification in XC cells and that pH-independent virus infections occur through endosomes in these cells.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0026180
 

Tony Mach

Show me the evidence.
Messages
146
Location
Upper Palatinate, Bavaria
I'm no expert, but to me this sounds like they looked how P/X/MLV/XMRV viruses infects certain cells. Specially what influcence the pH of the endosome (how "acid" a certain part of the cell is) is with regards to an enzym called "cathepsin protease". Don't know if this is an viral enzym, or a human enzym though, and what role it plays with regards to XMRV.

Molecular mini-micro-pico-research at its best, I presume. It is like the joke about the three blind men, who try to describe what an elephant is: "It is a tail!", "No, it is a trunk!" and "No, it is a leg!". Only here, they looked at an hair of the elephant.

Doesn't matter. It's a blind alley with regards to ME/CFS.
 

Jemal

Senior Member
Messages
1,031
Thanks for your reply Tony, it makes some more sense now. I am not so sure this is a blind alley, though.
 

Deatheye

Senior Member
Messages
161
Cathepsins (Ancient Greek kata- "down" and hepsein "boil"; abbreviated CTS) are proteases: proteins that break apart other proteins, found in many types of cells including those in all animals. There are approximately a dozen members of this family, which are distinguished by their structure, catalytic mechanism, and which proteins they cleave. Most of the members become activated at the low pH found in lysosomes. Thus, the activity of this family lies almost entirely within those organelles. Although there are many exceptions. Such as cathepsin K which works extracellularly after secretion by osteoclasts in bone resorption.

http://en.wikipedia.org/wiki/Cathepsin