4 ms·

Actual citation: http://www.ncbi.nlm.nih.gov/pubmed?term=23298160 http://www.ncbi.nlm.nih.gov/pubmed?term=23298160 The full-text article is behind a paywall :-

• InclinedPlane 14y ago
  I'm not very familiar with viral mediated gene therapy, is it reasonable to assume that it would be possible to infect enough T-cells with the virus to overlap a significant portion of the HIV infected cells? And if so, is that achieved by having the viral vector spread rapidly as well? Wouldn't that be nearly as damaging as the HIV infection to start with? Or is the goal to try to introduce entire modified HIV genomes into cells and then have those be fortuitously replicated and bound into HIV particles which will hopefully go out and re-infect other T-cells and in the process inhibit the HIV production rate?
  • shiven 14y ago
    HIV, being a retrovirus, acts by inserting its genome into the infected cell's nuclear DNA. The infected cell is unable to distinguish it from its own 'native' DNA. This is a fundamental aspect of how the cellular machinery is hijacked by the virus to replicate itself. Now, nearly a tenth of the human genome is made up of retroviruses (ERVs) that got inserted into our genome over the course of our species' (rather short) evolutionary history [0]. These ERVs were rendered dormant by genomic silencing of entire swaths of the genome (by mechanisms too detailed to go into here) turning them into 'harmless', silent blocks of genetic code we now carry in every cell! is it reasonable to assume that it would be possible to infect enough T-cells with the virus to overlap a significant portion of the HIV infected cells? That is the basic assumption, but is not guaranteed to happen. Specifically because a sub-population of infected T-cells, called the 'reservoir' population, are 'sleeping' in the bone marrow or the brain (and numerous other organs), waiting for signals from the immune system to activate them into action, which may happen due to an unrelated infection (or other reasons). This sub-population of cells, once called into action, will start running their usual gene expression program, resulting in the production of new viruses and infection of new cells. This is the NP-hard problem of HIV therapies! Or is the goal to try to introduce entire modified HIV genomes into cells and then have those be fortuitously replicated and bound into HIV particles which will hopefully go out and re-infect other T-cells and in the process inhibit the HIV production rate? In a word, yes. But there are too many moving parts to have the whole shebang fly off the handle and cause unintended or unexpected actions. Gene therapy, in its current form, has its place in the pantheon of medicine, but HIV is probably not a very good problem to attack with this approach, partly for reasons I mentioned above. The future of gene therapy holds the definite promises of miracle cures, which will be possible after more research and development (but only made possible by your tax dollars) ... [0] http://en.wikipedia.org/wiki/Endogenous_retrovirus http://en.wikipedia.org/wiki/Endogenous_retrovirus