Friday, April 6, 2018

IgG2 hypotheses requests the role of 25HC to be examined.

How does IgG2 work?





The question is how does the IgG2 find the infected host cell? Is the viral RNA somehow loosely held on the surface?

Cytosolic viruses trigger IFNbeta which could do 2 things : increase macrophage consumption of virally infected cells using tyro3  and secondly increase complement...somehow.

(note that viral infections that move into the mitochondria or nucleus would trigger HLA-A/B and CTL pathways)

IFNbeta changes the plasma membrane...more rigid
https://www.ncbi.nlm.nih.gov/pubmed/6180094

IFNbeta decreases plasma cholesterol levels
http://n.neurology.org/content/62/5/829

flu and complement
http://jvi.asm.org/content/81/7/3487.full

https://books.google.com/books?id=D5c-DgAAQBAJ&pg=PA11&lpg=PA11&dq=flu+igG2a+plasma+membrane+complement&source=bl&ots=p9xouclFrD&sig=Ek5c3_YvwQ8CVMUsVrHlLvW1aD8&hl=en&sa=X&ved=0ahUKEwivh6fwmabaAhWJiFQKHYmgAIYQ6AEISzAF#v=onepage&q&f=false

 IFNbeta triggers macrophages to produce and secrete 25 hydroxycholesterol (25 HC)

Do cells take up the 25HC which binds RNA in their cytosol and holds it on the surface for IgG2 complement?

25HC makes the plasma membrane more rigid which could prevent viral infections from starting but it seems to also block existing infections

I can find evidence of 25HC slowing viral replication but no evidence of direct binding of RNA or  25HC taking RNA viruses to the plasma membrane outer surface...still looking.

If the viral RNA is bound by 25HC and held at the plasma membrane is it then recognized by IgG2 is that when a pore is made leaking the host cell?

macrophages produce 25HC with IFN from viral infections
https://www.ncbi.nlm.nih.gov/pubmed/23273843?dopt=Abstract&holding=npg

How 25HC is thought to function
http://www.cell.com/immunity/abstract/S1074-7613(12)00510-9

25HC also protects against zika
http://www.cell.com/cms/attachment/2118940218/2087006181/mmc1.pdf

Does 25HC bind the RNA and then hold it on the plasma membrane for IgG2?

IFNbeta also tells macrophages to express tyro3 receptors. Macrophages will engulf only these virally infected cells?

Zika and tyro 3
http://medcraveonline.com/MOJPB/MOJPB-03-00088.pdf

some flu viruses actually try to avoid being eaten by macrophages by down regulating tyro3
http://jvi.asm.org/content/89/5/2672.full

25HC blocks HCV's  RNA replication
https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.27913
Does it bind the RNA of the virus???

cholesterol binds and inhibits SCAP directly but 25HC does not
https://www.ncbi.nlm.nih.gov/pubmed/15452130

What does 25HC do?

Note that M1 macrophages secrete 25HC which matches up with the TH1 cells.

structure of 25HC
http://www.chemspider.com/Chemical-Structure.58604.html

How does the 25HC hydroxyl group capture viral RNA? through the Sugar-phosphate backbone?






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