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how the nucleocapsid neutralizes antibodies
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how the nucleocapsid neutralizes antibodies

i would like to ask all you molecular biology experts to comment on how the nucleocapsid evades antibodies from eliminating the viron? does the icosahedron shape of the capsid benefit this process?

i have some ideas that have a few holes in understanding this process. would love a discussion.

Whrose
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Avatar_dr_m_tn
In the mature virion, the nucleocapsid is surrounded by the viral envelope, like in all enveloped viruses. It is like a ball inside a second larger ball - the envelope. Surrounding even the envelope, as i pointed out earlier, are also many lipids that HCV uses to escape even a ( theoretically effective) neutralizing antibody binding by antibodies against the envelope proteins.

So no antibodies against the nucleocapsid have a chance to bind to the virions - its deep inside, only liberated from the envelope once it has crossed the hepatocyte membrane to reenter /infect a new hepatocyte, where the "uncoating"  process occurs as an early step in the intracellular part of the viral life cycle.

That does not mean that there are no plasmatic circulating antibodies against the nucleocapsid. In the process of viral degradation in the peripheral sites of the body where the vast majority of the secreted virions become "debris" at a rate of a trillion dead viral bodies to be dismantled per day, th envelope is stripped from the nucleocapsid, exposing its inherent B-cell epitope to the antibody producing arm of the adaptive immune system.

Therefore, in the course of this dismanteling/partly spontaneous decay of the virons, the nucleocapsid will also become exposed to the B-cell system, triggering the production of antibodies - but of no major significance to the HCV fighting process, since those capsid/"core" specific antibodies simply have no access to the intact circulating virions and cannot prevent reinfection.

. They do have access to the capsids of the virions that fall apart - and  yes they fall apart a lot- but that has at first maninly  negative consequences to the patient, since the resulting immune complexes burden the removal system and trigger complement reactions at thre site of their disposal in the systemic circulation hence many of the extrahepatic inflammatory manifestations of HCV disease.
The only upside to this capsid/antibody complex formation could be that these complexes are also preferentially picked up and processed in the dendritic cells and macrophages, resulting in epitope processing for both calss I and II reactions. This might have, particular when interferon is used, a certain role in the rekindling of class I and II T cell responses against capsid residing peptide sequences -"epitopes" that are  - for class-  I then actually been recognized on the surface of infected hepatocytes by the cognate, epitope specific T cell receptor.

Please align these here mentioned features with the prior description of the general mechanisms of immune defense against HCV, as briefly described in the thread re "cell to ceel transfer of HCV" that contained the eroneous BBC article purporting a role of antibody defense in HCV  that does not exist.
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Avatar_n_tn
thanks you for giving me the cement i so needed in my notes!
will take more time in the review of this all as it has been my favorite topic to explore.
in my notes i had the capsid listed to
affect cellular immunity
cell growth/apoptosis
cell transformation
downtregulates MHC11 molecules in B cells
impaires antigen processing and presentation

i felt confused for sometime trying to figure out how the capsid comes into contact with antibodies considering it is overlayed with the envelope. you did it again....plugged another hole in my understanding.

also curious about the association of the core protein and lipid droplets within the cytoplasm.
is this why hcv perhaps affects lipid metabolism and the genesis of steatosis by creating > lipids for its use which then promotes storage in the liver. also causing  serum dyslipidemia?

hugs
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Avatar_dr_m_tn
also curious about the association of the core protein and lipid droplets within the cytoplasm.
is this why hcv perhaps affects lipid metabolism and the genesis of steatosis by creating > lipids for its use which then promotes storage in the liver. also causing  serum dyslipidemia?

Glucose and fatty acid molecules have to be processed in terms of energy metabolism, but also in terms of providing intermediates for several synthetic/anabolic pathways  in the mitochondria of the heaptocyte.
Since the  HCV core protein, by mechanisms not entirely clear, has a prooxidative/damaging role to the hepatocytes mitochondria, the speed/ efficacy -technically called "flux'-  through these mitochoindrial pathways is impaired/slowed.

As a result there is a backlog of glucose and pyruvate/acetylCoenzymeA in the cytoplasma that will direct those metabolites into the cytosolically located fatty acid/triglyceride (FAT) synthesis pathways.

In short; can't burn it well in the damaged mitochoindria, lets make fat of it, what elso to do with it. Thus in this way your LIPID DROPLETS are created in the hepatocyte cytoplasm. Never a good thing for the liver cell to have fat droplets in its interior work space. Imagine a factory hall, where all the shipments of materials that normally are worked up in the next hall are now stored right in the middle of the workspace and everybody has to cumbersomly walk and work around these very bulky hindrances.....


Whether the virus takes relevant additional survivial/replication/reinfection advantage from these increased amount of .lipids in other ways and has therefore worked his evolution towards this is entirely speculation...
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Avatar_dr_m_tn
Sorry for the typos, have to be fast .It is neither "mitochoindria" nor is it "survivial".
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