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TOPIC: Virus Life Cycle Questions

Virus Life Cycle Questions 5 years 8 months ago #21450

  • sb409us
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As I push forward after treatment, I wonder what might be the cause(s) of the side effects I now experience. Here are my questions.

1) How long does a Hep C virion live in the human body if nothing interferes with it's life cycle?
2) What happens to the virions whose NS5B enzyme and NS5A protein have been inhibited by Harvoni? Do they continue to live? Do they die? If so, how and when are they eliminated from the body?
3) What does the RNA Quantitative test use to identify a virion? For example, could there be virions with inhibited enzymes and proteins still living in the body but not detected by the test? What markers need to be present for the test to identify a Hep C virion?
4) How are various host cells affected by Harvoni? Are cell membranes weakened or even dissolved?
5) Does Harvoni block hyperphosphorylation in host cells? Affecting mitosis of host cells?
6)What affect do Ledipasvir and Sofosbuvir metabolites have on host cells? What is the half-life of the metabolites and how are they eliminated from the body?

I find it interesting that, so far, no one in the hepatology field can answer these questions. Someone must know. If not, why would they let us put Harvoni into our bodies? Thank you in advance to anyone who can provide some accurate answers.
GT 1a
Fibrosis 2
Age 55
Started Harvoni tx 6/21/2016
4 week labs Undetected
EOT 8/15/2016 Undetected
Last Edit: 5 years 8 months ago by sb409us.
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Virus Life Cycle Questions 5 years 8 months ago #21453

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Follow up on my above topic. The reason I would like to know the answers to these questions is to help guide my recovery/healing. It's hard to know how to treat symptoms without knowledge of their cause.
GT 1a
Fibrosis 2
Age 55
Started Harvoni tx 6/21/2016
4 week labs Undetected
EOT 8/15/2016 Undetected
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Virus Life Cycle Questions 5 years 8 months ago #21463

  • DrJames
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Hello SB

This is a good video:



1) Indefinitely, but the virus is not really alive. It is a piece of self assembling genetic code. "Floating around in the blood" it is assembled. On cell entry the envelope is shed and it "Falls to bits", then there is replication/reassembly and exocytosis. There is a lot of waste. All the negative strands of RNA go to waste and are digested and recycled. A lot of the proteins suffer the same fate. The replicon unit has a lifespan of about 4 weeks (inhibited) but this is a half-life meaning it is an exponential decay over time with 1/2 at X units of time, 1/4 at 2 X units of time, 1/8 at 3 X units of time, etc
2) NS5B inhibition by Sofosbuvir is suicide inhibition - the sofosbuvir binds permanently rendering that replicon inactive. In time it will decay and be recycled. NS5A inhibition is transient, ie only while the drug is at a sufficient concentration, and it works by competing for space like a night club security person standing in a door blocking entry.
3) We use the Polymerase Chain Reaction to clone the HEP C RNA. We then look for specific target sequences in that RNA using probes that are like the mirror image of what we want to find.
4) Some membrane is used by the virus for it's capsule. Cell death occurs when the body's immune system recognises the infection and destroys the infected cell. This releases enzymes from inside liver cells like ALT/AST. Many cell lines (other than liver cells) are infected, thus the extra-hepatic manifestations
5) Harvoni is 2 things. Sofosbuvir suicide inhibiting NS5B and Ledipasvir competitively inhibiting NS5A. The drugs are well targeted at viral proteins but almost certainly bind to some host protiens and cause issues. These issues produce the side effects and depend on the genetics of the patient. The drug trials establish that we can successfully kill the virus without accidentally killing the patient. This is the trick with new drugs - get the effect desired without (too many) side effects.
6) Sofosbuvir is a pro-drug. It has no effect on anything and needs to be phosphorylated (twice) by CES1 and CatA to become the active metabolite GS-331007 which has a 1/2 life of 27 hours and exits via both the liver and renal (kidney) excretion - thus the problem with Sofosbuvir in renal failure patients.

I expect you may enjoy the detail in the European Medicines Agency Public Assessment Report:

www.ema.europa.eu/docs/en_GB/document_li...3850/WC500177996.pdf
YMMV
Last Edit: 5 years 8 months ago by DrJames.
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Virus Life Cycle Questions 5 years 8 months ago #21473

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Thank you so much, Dr. Freeman. I appreciate that you provided this information to me, a non-medical person. I do have a propensity for analyzing and am driven by the need to understand. I went from being an electronics technician to special education teacher (middle school science) to educational diagnostician, all areas that require an analytical mind. Again, thank you. I appreciate that you did not pat me on the head and tell me to leave this to the professionals. It's quite refreshing, to say the least.
GT 1a
Fibrosis 2
Age 55
Started Harvoni tx 6/21/2016
4 week labs Undetected
EOT 8/15/2016 Undetected
Last Edit: 5 years 8 months ago by sb409us.
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