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ERVs: link between intestinal microbiota and various diseases

natasa778

Senior Member
Messages
1,774
I haven't been able to find a link to the full version, shame as sounds interesting - including the bit on the new data mining tool!
http://discovery.ucl.ac.uk/1404381/

... ERVs exerted a significant influence on the immune response, a mechanism that may partially contribute to the heterogeneity seen in human immune responses to retroviral infections. Secondly, a requirement for specific antibodies was shown in the control of ERVs. In a range of mice displaying distinct deficiencies in antibody production, products from the intestinal microbiota potentially induce ERV expression. Subsequent recombinational correction of a defective murine leukaemia virus (MLV) results in the emergence of infectious virus. In the long term, this leads to retrovirus-induced lymphomas and morbidity. ERVs, therefore, provide a potential link between the intestinal microbiota and a range of pathologies, including cancer. Finally, a new computational tool, REquest, was developed for use in the above studies. REquest allows the mining of retroelement (RE) and ERV expression data from the majority of commercially available human and murine microarray platforms and allows rapid hypothesis testing with publicly available data.
 

anciendaze

Senior Member
Messages
1,841
Subsequent recombinational correction of a defective murine leukaemia virus (MLV) results in the emergence of infectious virus.
We have here, once again, the odd hypothesis of recombination in the absence of any replication-competent retrovirus to start the process. Recombination which has been studied in the lab involves crossover between similar strands which are packaged together in a single virion. These probabilities are quite high for organisms with trillions of cells containing ERVs, even if the number of replication-competent retroviruses at the start is very small. Without any replication-competent virus at the start it is hard even to guess at probabilities that transcribed sequences will recombine into a replication-competent retrovirus which somehow inserts provirus in chromosomes.

We have previously seen data on retroviruses in lung secretions thrown out on the grounds that this must be contamination by exogenous viruses which do not infect cells in the body, even if they are able to infect similar cells in vitro. Here we see similar reasoning involving microbiota of the gut. Both environments are patrolled by host immune cells which can then carry inserted provirus back through the bloodstream without having virions destroyed by antibodies. The hypothesis that a later breakdown in ability to hold the provirus latent in previously infected immune cells would result in precisely the recombinations and emergence of infectious virus specifically affecting immune response as described above must not be one that is even allowed to be considered.
 

anciendaze

Senior Member
Messages
1,841
Treatment is some distance off, we're still at the stage of recognizing the problem, but I could sketch out a couple of ideas.

First, at early stages of some diseases suspected of such causes, it might be worthwhile to consider antiretroviral drugs. This has been happening piecemeal, but a more systematic approach, in diseases that show ERV activation, would make sense.

Second, if the idea that the start of the process requires a replication-competent virus, already present in the host, pans out it would make sense to specifically target such infected cells while the number is small. There would be two problems: 1) most of these are latent, most of the time; 2) you would need a very narrow therapeutic target to avoid extensive damage to uninfected cells. The treatment would then consist of a means of provoking those latent infected cells to express the provirus in a way that would allow immune targeting, followed by a highly-specific targeted immune response, as we see in adoptive immunotherapy. (Where the patient's own immune cells are extracted, stimulated in vitro for a specific target, cultured into larger numbers, then returned at a rate the patient can tolerate.)

Simply being able to test individuals to see which ones are most at risk, because they carry a latent infection, would be a great advance.

It is still very early days to be talking about this. I'm just trying to show that it is possible to imagine treatments. Almost certainly, the methods worked out after more experience would be different, more efficient and less costly.
 

anciendaze

Senior Member
Messages
1,841
Firestormm, a PhD. dissertation must make a significant contribution to the state of the art to be accepted. I've seen some fairly amusing reasoning along those lines, but I do not think that is going on in this case. If you are thinking of studies on treatment of patients, that would be way down the line, but this is almost certainly based on considerably more than library research and speculation.

We won't know until the full text is available. It appears release of this text is being withheld pending presentation or publication in another form.