According to research recently published by a team of Hopkins researchers, saving trees may have other benefits in addition to creating a greener planet.
Although trees and other plants are crucial for purifying the air, a significant portion of pharmaceuticals are derived from these leafy organisms. But only recently did the Hopkins team learn that a molecule from the black walnut tree could potentially help eradicate AIDS in conjunction with some of the latest AIDS treatments.
Today, approximately 33 million people have Acquired Immune Deficiency Syndrome, commonly known as AIDS, which is caused by the Human Immunodeficiency Virus (HIV).
Although many treatments currently exist to help diminish the effects of AIDS temporarily, a permanent solution has not yet been found. Scientists around the world have been studying how the virus works to cause AIDS, hoping that an understanding of the mechanism may lead to a cure.
Currently, the most effective treatment for HIV was HAART, which stands for "highly active anti-retroviral therapy." HAART suppresses HIV through its combination of medications and has greatly improved patient outcome. However, it does not cure the infection. Instead, HAART leaves reservoirs of the latent HIV in memory CD4+ T cells, a type of cell involved in the body's immune system.
"Because of the longevity of memory T cells, latent virus can last almost lifelong in the infected individuals," Hung-Chih Yang said, a professor in the Hopkins Department of Medicine and the lead author of the paper.
"The latently infected CD4+ T cells are indistinguishable from the uninfected cells, so they can escape from host immune clearance."
Once the HAART treatments are over, the latent cells can awaken from their dormant states, and become active in producing infection. While some would say that it is possible to remain on HAART for life, it is not practical to do so because of its side effects and potential toxicity.
According to Yang, the next frontier in the search for the cure for AIDS would be eradicating the latent cells. Currently, vaccines and gels that have been created to eradicate the latent reservoirs have failed.
In order for the latent cells to be eliminated, they must first be activated so the virus can be detected by the body's immune system. But there are complications that can arise when activating the HIV.
"Although T cell activation signals can activate HIV replication, previous studies have demonstrated that the strategy involving induction of T cell activation is too toxic," Yang said.
As a result, a specific activator was needed so that only the CD4+ cells containing the latent virus would become activated.Like most research on disease, laboratory trials must precede clinical trials. Yang and his team managed to create a model for latency before testing possible activators. Simply putting the resting CD4+ cells in a culture would not work because they do not survive for a long enough amount of time without certain stimulating chemicals which would make the model inaccurate.
"The success of our primary cell model relies on the introduction of Bcl-2 into resting CD4+ T cells," Yang said. "Bcl-2 is an important survival factor for resting T cells." When cells over-express the gene for Bcl-2m T cells are able to survive for months without needing any stimulators.
Furthermore, the Hopkins researchers were able to create viruses that would increase the amount of T cells that could hold latent viruses. "We also generated a genetically modified HIV that has low toxicity to infected cells," Yang said. "Due to the low toxicity of this genetically modified virus, we can obtain larger number of latently infected cells."
To find a compound that would awaken dormant HIV without activating T cells, Yang and his team screened small molecules from a library of 2000 drugs and natural products and another set of 2400 compounds from the Hopkins Drug Library.
Nine compounds were found from the first set and the Hopkins Drug Library turned up eight. However, both sets included the molecule 5-hydroxynaphthalene-1,4-dione, also known as 5HN, which comes from the leaves, roots and bark of the black walnut tree.
5HN also had the highest capacity to reactivate the latent HIV, but did not cause the global T-cell activation that is so toxic in the clinical trials. Because 5HN can reactivate the latent HIV, HAART drugs can subsequently be used to treat and potentially eliminate the newly reactivated HIV.
While the use of 5HN on an in vitro model is a novel and promising venture towards the cure for HIV, issues still remain. 5HN may be too toxic for humans, so although the results seem promising in the lab, clinical trials may not yield such positive results.
Furthermore, other recent studies indicate that there may be more underlying latent reservoirs of HIV that would need additional experimentation before reaching a cure.
However, Yang is optimistic about the discovery of 5HN's effects on their in vitro model. "This platform can facilitate the discovery of more appropriate compounds that can potentially cure HIV," he said.
