HIV poses a great challenge to researchers because of the way it uses the human immune system to grow and multiply: the more the body tries to combat the virus, the more HIV can replicate. Hopkins researchers, however, recently made a major leap in understanding the virus’ mechanisms. They discovered 25 proteins, which they believe are critical in the process of infection with HIV-1, the most common form of the virus.
“The question that we were asking was how proteins are packaged into virus from either macrophages or T lymphocytes, the two major cell types that HIV infects,” senior author David Graham, an assistant professor of pathobiology at the Hopkins School of Medicine, said.
“We were asking what proteins would be common between those two different cell types that would give us an indication of what was really critical to the HIV life cycle and hopefully refine the targets of what we would look to for potential therapeutics.”
In order to identify these 25 proteins, the researchers had to purify HIV to verify which proteins came from the virus and which did not. The process of isolating particles was especially challenging due
to the presence of contaminants and vesicles that co-purify with HIV.
“We had to spend a number of years on developing some new methods that would allow us to purify HIV and separate it from all of those particles,” Graham said.
The implications of this research are far-reaching. The discovery will allow researchers to further explore the proteins themselves and also the protein-virus interactions that are crucial in the HIV life cycle. However, the discovery is not limited to knowledge about viruses and proteins.
“One of the big questions that we still have and don’t know the answer to is what are the cells that harbor virus in latent viral reservoirs. The methods that we’ve created here will allow us to identify what cells harbor virus and hopefully once we do that, we can figure out a way to get virus out of those cells,” Graham said.
These reservoirs store hidden supplies of the virus and make it extremely difficult for HIV treatment (antiretrovirals) to wipe out all traces of the virus. If the cells that hold these reservoirs could be identified, researchers would be much closer to discovering a cure for HIV.
Graham stated that the complexity of HIV is beyond what many people imagine.
“Not only does it steal proteins from our cells, but it also arranges those proteins in ways similar to how our body works and it mimics the functions of those proteins in our body,” Graham said. “HIV is doing a lot of masquerading and imitation of our own immune system, and that is one of the ways that HIV causes disease.”
The discovery at Hopkins has brought researchers closer to understanding not only the significant proteins involved in HIV infection and their arrangement, but also possible approaches for finding a cure for this complex and challenging virus.
