In a breakthrough, Australian researchers have developed a method to boost the immune system. This technique is seen to be capable of clearing an “HIV-like” infection from a mouse. This could in future lead to a cure for HIV and other chronic viral infections in humans. The findings from Melbourne’s Walter and Eliza Hall Institute are centred on a naturally occurring cell signalling hormone called interleukin-7 (IL-7).
Lead researcher Dr Marc Pellegrini explained that when a synthetic version of this hormone was given to mice it “boosted the immune response in a pretty profound fashion” – so much so it cleared a virus considered a close match to HIV. Dr Pellegrini said, “We’ve shown that persistent use over three weeks can actually clear infection and we would presume that this would be translatable to humans… This is the first time that we’ve used (IL-7) therapeutically to cure an infection and it looks like it is translatable to HIV.”
Dr Pellegrini worked with colleagues Mr Simon Preston and Mr Jesse Toe, and collaborators Professors Pamela Ohashi and Tak Mak from the Ontario Cancer Institute. Their findings were published today in the journal Cell.
IL-7 performs an important role in immune system development and maintenance, and the extra dose on the mice improves the immune system’s killer T Cells, which seek out and kill off foreign viruses. The good part is that the immune system did not go haywire attacking healthy parts of the body in a damaging auto-immune response. The team hopes that this boosting effect would be sufficient to be used with conventional anti-retroviral drugs to kill off the HIV virus. This system will aid the human immune system clear the body’s “latent reservoirs” of HIV. These are pockets of usually inactive HIV virus which are known to exist in a HIV Positive person’s gut and brain.
Further investigations revealed that, at the molecular level, IL-7 switched off a gene called SOCS-3. “In an overwhelming infection, SOCS-3 becomes highly activated and suppresses the immune response, probably as a natural precaution to prevent ‘out-of-control’ responses that cause collateral damage to body tissue,” Dr Pellegrini said. “In the case of these overwhelming infections, the immune system effectively slams on the brakes too early, and the infection persists.”
Mr. Preston, who worked on the SOCS-3 studies, said that switching off the SOCS-3 gene boosted the immune system and helped the animals to completely eliminate the infection. “The key for us was figuring out that turning off SOCS-3 only really worked when it was within T cells,” Mr Preston said. “It allowed the immune response to boost the number of virus-specific T cells and have an immune response good enough to eliminate the virus without initiating an immune response that was too large and would make the animal sick.”
Dr Pellegrini said, “We know that we will never be able to effect cures with our current anti-retrovirals because it just kills the virus in the system but there are always going to be latent reservoirs that will come back into action as soon as you stop that therapy…Whereas IL-7 will reinvigorate the immune system and each of the T cells will be able to fight the virus much better … and, in theory, clear these latent viral reservoirs.”
However he added that it could still take 10 to 15 years before IL-7 could be approved for broad scale use to combat HIV. At present human trials have only shown that it is not initially toxic and more trials regarding effectiveness are warranted.
The technique could also help against hepatitis B and C, or bacterial infections such as tuberculosis, which also pose significant global health burdens.
This research was supported by the Australian National Health and Medical Research Council, the Canadian Institute for Health and the Cancer Research Institute.
By Dr Ananya Mandal