Despite significant advances in drug treatments, a cure for HIV continues to elude scientists. One of the main reasons for this is that HIV is capable of hiding within cells of our immune system, forming what is known as a latent reservoir. This pool is not only invisible to immune system soldiers, but is also unreachable by antiviral drugs. But now, new research suggests that scientists could be close to finally coaxing out the hidden HIV and destroying this lingering supply of the virus.
According to the study, the reason that waking up the dormant reservoir is insufficient to eradicate the virus from the body is because latent HIV mutates itself beyond recognition, rendering the immune system useless against it. However, all hope is not lost as the researchers demonstrated it is possible to train a type of immune system killer cell to be able to recognize these mutants, which then go on to destroy these infected cells.
Scientists from Johns Hopkins and Yale began their investigation by examining the DNA sequences of viruses from two different groups of HIV infected individuals: those that began therapy within the first three months of infection, and those that had been chronically infected prior to commencing drug treatment.
As described in Nature, they found that the latent reservoirs within patients that began therapy early tended to contain largely unaltered HIV, whereas those that started treatment later were dominated by so-called “escape mutations,” or variants that render infected cells insensitive to a type of immune killer cell called a cytotoxic T lymphocyte. The reason that these viruses avoid detection by these cells is because portions of one of the virus’ proteins are mutated beyond recognition. Around 98% of latent HIV in those that started therapy later carried these escape mutations.
However, they also found that these viruses still retained sections of the original protein that were unaltered, which led the researchers to ponder whether it might be possible to nudge the immune system to spot these tiny segments and thus destroy the infected cell. To begin the training process, the team first isolated killer cells from infected patients and added them to either fragments of mutated HIV protein, or a cocktail of mutant protein alongside non-mutated protein. A few days later, they exposed the killer cells to cells infected with HIV isolated from patients harboring escape mutants.
They found that cells trained with the mixture of proteins were able to mount a broad and effective response against HIV, targeting the unmutated portions of HIV proteins. This resulted in the destruction of 61% of infected cells, compared with only 23% when cells were exposed to only mutated proteins.
Next, they took this one step further by using HIV infected humanized mice (mice engineered to be more physiologically similar to humans) instead of cells in a dish. They found that mice injected with killer cells trained by the mixture of HIV proteins were able to control infection, and some mice even cleared the circulating virus. According to the researchers, these results suggest that this technique could act as a blueprint for the development of a therapeutic vaccine to eradicate HIV.