I noted that the failure to properly traffic lipoprotein cholesterol in NPC1 results in impaired oxysterol and steroid synthesis. The authors found that treatment of Npc1 -/- mice with the neurosteroid allopregnanolone and a synthetic oxysterol ligand delayed the onset of neurologic symptoms and prolonged life span, suggesting that the treatment bypassed the cholesterol trafficking defect. The therapy preserved Purkinje cells, suppressed cerebellar expression of microglial-associated genes, and reduced infiltration of microglia in cerebellar tissue. Transfection assays correlated the efficacy of treatment with activation of murine PXR (NR1I2; 603065) in vivo.
The members of the family Filoviridae, Marburg virus (MBGV) and Ebola virus (EBOV), are very similar in terms of morphology, genome organization, and protein composition. To compare the replication and transcription strategies of both viruses, an artificial replication system based on the vaccinia virus T7 expression system was established for EBOV. Specific transcription and replication of an artificial monocistronic minireplicon was demonstrated by reporter gene expression and detection of the transcribed and replicated RNA species. As it was shown previously for MBGV, three of the four EBOV nucleocapsid proteins, NP, VP35, and L, were essential and sufficient for replication. In contrast to MBGV, EBOV-specific transcription was dependent on the presence of the fourth nucleocapsid protein, VP30. When EBOV VP30 was replaced by MBGV VP30, EBOV-specific transcription was observed but with lower efficiency. Exchange of NP, VP35, and L between the two replication systems did not lead to detectable reporter gene expression. It was further observed that neither MBGV nor EBOV were able to replicate the heterologous minigenomes. A chimeric minigenome, however, containing the EBOV leader and the MBGV trailer was encapsidated, replicated, transcribed, and packaged by both viruses.
Dear dean,
Thanks for your valued findings. As you know EBOLA virus has multiple strains , meaning an immune response is needed against all of them in order to full protection.
Meanwhile, Ebola’s ability to replicate rapidly could mean the virus may rapidly evolve resistance against a vaccine. So, according to your findings, establish an effective EBOV vaccine would be impossible. Am i right?
Dear Mr Zorriehzahra,
The idea of Ebola's rapid idea that it has human to human mutation evolvement gives reason to why the U.S is requiring to have person's in question transported back to the states for this research and to research a human vaccine to manufacture its resistance, of the many stains involved It is to my understanding that Fibroblasts from patients with NPC1 mutations, human monocytes and endothelial cells and green monkey kidneys cells treated with U18666A, or human endothelial cells in which NPC1 had been knocked down exhibited reduced infection with authentic Ebola or Marburg virus. Npc1 +/- mice were largely protected from mouse-adapted Ebola or Marburg virus, whereas wildtype mice rapidly succumbed to infection. this is a great start to working on a vaccine in my mind but without full access to a C.D.C. Bio laboratory to research my findings further it is hard to speculate my required answers, I do not think it is impossible per say to manufacture a viable vaccine, As with H5N1 anything can be possible with a controlled Bio Lab and the right people time is on the other hand the key? thank you for your time Jalil
Dear Mr. Dean,
Thanks for your explanation. It was great findings. What about Mab treatment in patients?
As you know treatment is very difficult in Viral Diseases so what can we do for victim people?
No vaccine no treatment! it seems a new tragedy is coming now!
What about your opinion about recombinant vaccine? is it a dream?
Thanks in anticipated
Kind regards
Jalil
Mr Zorrriehzahra,
Regards to Mab treatments in patients, well again not having such an outbreak as is flowing through reports now, to use such idea's and develop such vaccines cannot be done without such labs as the CDC or a pharmaceutical company looking to produce a sound vaccine, perhaps in the future?
Viral Diseases are and has always been very difficult to treat as I am shore you know isolation and control would be the key at present, but having to many Indians and not enough chief's can be a even bigger problem with merging times as this,
As to your recombinant vector vaccine question, there has been lots of talk about this with other scientists I talk with and will be a huge developing factor in the vaccine industry, as they have already been working on both bacterial and viral based recombinant vector vaccines for measles and HIV These carrier viruses just ferry the microbial DNA to cells and the recombinant vector vaccines do closely mimic a natural infection and then largely stimulating the human body to immune system defence, Attenuated bacteria also can be used as vectors. In this idea the neatly inserted genetic material causes the bacteria to display the antigens of other microbes on its surface, effectively the harmless bacterium mimics a harmful microbe, provoking an immune the response in the human body, But as we start playing god with these and many more new ways of fighting disease there will be simple factors that will be missed once DNA mutation starts been developed to become sterile from disease, But there was nothing ever wrong with playing in the mud as a kid either and mother nature has yet to let us know of all her secrets
pleasure talking with you Jalil
Kindest regards
Dean
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