Posted on January 09, 2015
Source: Johns Hopkins Medicine
Luring dormant HIV out of hiding and destroying its last cure-defying holdouts has become the holy grail of HIV eradication, but several recent attempts to do so have failed. Now the findings of a Johns Hopkins-led study reveal why that is and offer a strategy that could form a blueprint for a therapeutic vaccine to eradicate lingering virus from the body.
The findings, published online Jan. 7 in the journal Nature, show HIV eradication efforts have been stymied by the virus’ ability to mutate beyond recognition, rendering it impervious to immune system destruction even when lured out of hiding. Going a step further, the scientific team successfully trained the immune system to recognize, attack and subdue such mutant HIV once coaxed out of its dormancy.
In a description of their “proof of principle” research, the team says they tamed mutant HIV by training a class of immune sentinel cells known as killer T cells to spot and eliminate HIV-infected cells capable of evading immune surveillance and impervious to immune system destruction.
The strategy addresses one of HIV’s most challenging behaviors — its ability to hijack a class of immune cells known as memory CD4+ T cells, where it goes into hiding soon after infection, lying quietly under the immune system’s radar and unreachable by antiviral drugs. The killing of those last infected cells has become the focus of numerous recent efforts to lure the virus out of dormancy and finish it off permanently. However, the new findings show much of the latent virus is not merely out of reach, but also genetically altered to evade recognition by the immune system even once latency is reversed.
“Our results suggest that luring HIV out of hiding is winning only half the battle,” says senior investigator Robert Siliciano, M.D., Ph.D., professor of medicine, molecular biology and genetics at the Johns Hopkins University School of Medicine. “We found that these pools of dormant virus carry mutations that render HIV invisible to the very immune cells capable of disarming it, so even when the virus comes out of hiding, it continues to evade immune detection.”
