We’re excited to have one of our newest board members contribute to this issue of The Update! They have offered to break down the often complex news that comes out of the medical field into terms we can all understand.
Happy fall, fellow PWAC members and friends! With this new season comes new research and breakthroughs relating to the control and treatment of HIV/AIDS. I have been asked to help break down the big stories in the research realm and share the discoveries with you all each month. This month, I have selected three separate articles to discuss, each having made great strides in the clearance/eradication of the virus in the lab. Each group has a great deal more work to do, but the news is exciting nonetheless!
First up, I am going to discuss work performed at the Picker Lab at the Oregon Health and Science University, in which they were able to completely clear SIV (Simian Immunodeficiency Virus) from monkeys, the virus that causes AIDS in this species (Hansen et al., 2013 . The researchers at the Picker Lab utilized an interesting approach to treatment; instead of using drugs to prevent viral replication, they utilized a genetically engineered version of a common virus, cytomegalovirus (CMV), to trigger a stronger and maintained immune response from effector memory T cells. These cells have the ability to “remember” harmful pathogens indefinitely This is the technique employed by many vaccines to provide long-term protection. Unfortunately, the typical immune response to the wild-strain SIV/HIV is not effective at clearance of the virus. The altered CMV used in the Picker Lab expressed specific SIV proteins, and the body responded by introducing new T -cells that have the ability to successfully identify and destroy SIV- infected cells. These new T-cells then act as “security guards” and work to clear the threat, in time eliminating the virus from the body. Although only 50 of the animals in the study had full clearance, the group hopes to learn why this was and ultimately to develop an effective vaccine strategy in the future using this newly discovered data.
The next article to discuss comes from Rutgers New Jersey Medical School, lead by Michael Matthews and Hartmut Hanauske-Abel (Hanauske- Abel et al., 2013). Using in vitro (meaning “in glass”) cell cultures, they were able to determine the efficacy of using a common topical anti-fungal, Ciclopirox, as a means to eradicate HIV infected cells. Interestingly, the anti-fungal drug causes the HIV-infected cells to spontaneously commit “suicide” by blocking the critical functions of the mitochondria, the powerhouse of the cell. HIV-1 typically blocks this “suicide-pathway” (known as apoptosis) in infected CD4 cells, preventing the body from protecting itself. The introduction of this drug reactivates this natural cell behavior while leaving healthy, uninfected cells unaffected. Although Ciclopirox is already FDA approved, it’s for topical use only; so the researchers at Rutgers are eager to investigate a similar new drug, Deferiprone, which is aimed towards systemic use and is currently in human trials in Africa. This new drug has also shown efficacy in HIV clearance in vitro. Stay tuned to these folks; they are headed in the right direction!
The final article I have selected to discuss is one recently published by a team led by Cameron Abrams and Irwin Chaiken at Drexel’s College of Medicine (Contarino et al., 2013). Using a chimeric recombinantly engineered protein (a fancy way of saying a molecule or protein built from smaller pieces of molecules/proteins for a specific application), the group was able to activate HIV’s fusion trigger, providing the illusion that the virus is affixed to a healthy cell. This trigger then causes the virus to “pop,” or eject, its viral genetic material into the abyss of the human body, rather than into a healthy CD4 cell, essentially tricking the virus into “spilling its guts” harmlessly and dying. Unless the viral genetic material is delivered directly into a healthy CD4 cell, replication is not possible; thus viral load is ultimately suppressed. Very cool indeed!
Contarino, M., Bastian, A. R., Sundaram, R. V. K., McFadden, K., Duffy, C., Gangupomu, V., et al. (2013). Chimeric Cyanovirin-MPER Recombinantly Engineered Proteins Cause Cell-Free Virolysis of HIV-1. Antimicrobial Agents and Chemotherapy, 57(10), 4743–4750. doi:10.1128/AAC.00309-13
Hanauske-Abel, H. M., Saxena, D., Palumbo, P. E., Hanauske, A.-R., Luchessi, A. D., Cambiaghi, T. D., et al. (2013). Drug-Induced Reactivation of Apoptosis Abrogates HIV-1 Infection. PloSone, 8(9), e74414. doi:10.1371/journal.pone.0074414
Hansen, S. G., Jr, M. P., Ventura, A. B., Hughes, C. M., Gilbride, R. M., Ford, J. C., et al. (2013). Immune clearance of highly pathogenic SIV infection. Nature. doi:10.1038/nature12519