The human immune system contains multiple cell types which work together to rid us of infectious and harmful intruders, such as bacteria and viruses. When these foreign substances enter our body, a group of cells called phagocytes provide the first line of defense against them. These cells engulf (eat) the microorganisms and degrade them into small pieces. The phagocyte then presents these degraded pieces on its surface as an identifier of the foreign substance. This display trains other cells of the immune system to recognize the pathogen and mount a robust response to prevent future infections. This is why we rarely become infected with diseases, like the chicken pox, twice.
HIV is different than most viruses, however. Our body’s immune defenses are no match for the fast replicating and mutating virus, which specifically targets the cells of the immune system. It replicates its DNA in an erratic manner which causes the new generation of viruses to exhibit a slightly different shape than the previous generation. This creates a challenge for the immune system which relies on a pre-registered memory of the virus. Since the immune system relies on its memory to recognize the pathogen, the evolving nature of the virus allows it to evade the immune system and propagate incessantly. For this reason, it is not only difficult for the immune system to target this virus but also difficult for the virus to be targeted externally with vaccines and drugs.
The virus has a simple structure; it has a lipid coat (or envelope) surrounding the genetic material. The coat has a single protein, ENV, on its surface which binds to the CD4 receptors on host cells in order to gain entry into the cells, This interaction is analogous to a lock and key; the Env protein on HIV’s exterior is the key that fits into the healthy cell’s receptor (the lock), “opening up” the cell to infection by the virus. Since entry into the host cells is an important step for HIV infection, attempts at curing or halting such an infection have focused on using Y shaped proteins called antibodies to fit into the lock (CD4) and block the Env entry. Antibodies that bind directly to Env and prevent it from interacting with CD4 have also been developed.
Furthermore, a recent study by the Chen group at Harvard University studied the structure of the Env protein itself, and its ability to be used in vaccine development against HIV. Their work looked at the binding of HIV antibodies that had been previously developed to target both the Env protein and CD4 receptor. They found that the Env protein can bind to different sets of potential HIV antibodies, depending on the length of the Env protein. When the portion of Env that is inside the virus is shortened, the portion of Env outside the virus that binds CD4 shows different binding to sets of antibodies that it previously showed poor interaction with. These findings are promising, as they lead us to a better/improved understanding of the structure of Env and its ability to interact with potential vaccines, and take us one step closer to developing more potent ones.
Chen, J., Kovacs, J., Peng, H., Rits-Volloch, S., Lu, J., Park, D., Zablowsky, E., Seaman, M., Chen, B. June 25th 2015, “Effect of the cytoplasmic domain on antigenic characteristics of HIV-1 envelope glycoprotein”, Science, vol. 349, no. 6244, pp. 191-195