The terms "HIV" and "AIDS" are often used together and (somewhat incorrectly) interchangeably. But they describe different things: HIV is a virus, while AIDS describes a wide-ranging group of symptoms and diseases that take advantage of the damage HIV does to an infected person's immune system. Some people who contract HIV live for many years without developing symptoms of infection. So how does HIV, a virus, become the potentially life-threatening AIDS?
New research demonstrates that the virus "tricks" uninfected cells into taking their own lives. But there's good news: A drug that could help stop the process is currently being tested. It's a drug that takes a novel approach, targeting the host instead of the virus.
The Anatomy of a Killer
HIV invades CD4 T cells, also known as "helper" cells, white blood cells that fight infection. First, the virus attaches to the cell, injecting its genetic blueprint—contained on viral RNA—into the cell. Viral RNA uses an enzyme, reverse transcriptase, to make viral DNA. The DNA enters the T cell’s nucleus, hijacking the cell’s replication machinery so it can make copies of the virus.
AIDS develops as CD4 T cells begin to vanish, leaving the host unable to fight infections. In the early days of AIDS, scientists theorized the virus directly infected cells, causing them to die. But later, they learned the cells were disappearing even though they weren't actively infected with the virus. This created what was know as the "bystander" theory, or the idea that the virus killed off the cells around those it infected. This theory stemmed from the discovery that only about 5 percent of CD4 cells usually show active infection.
While an actual AIDS diagnosis is made based on a number of factors, a CD4 count of below 200 can be a qualifier. Healthy counts range between 500 and 1,000.
The Evolution of Progression Theories
Several years ago, a new theory emerged: that the immune system response was so intense, the cells became exhausted and simply wore out.
Then research centered around the thought that the few cells actively producing the virus were going after others in the neighborhood. In 2010, scientists learned more about a process known as “abortive infection,” whereby the virus would try to complete its lethal invasion and reproduction process but fail because the cell was at rest.
Now research says that most of the dying cells are actually infected as sleeping bystanders. Previously, the process was thought to be apoptosis, which results in an accelerated death of cells that allowed themselves to be invaded. The new thought is that cells are lured into the neighborhood and, even though complete infection fails, enough of the virus remains for the cells to detect it and end their own lives.
Warner Greene, a scientist at University of California, San Francisco's Gladstone Institute, published the science behind this discovery last month in the journals Science and Nature.
“The infection is aborted, the cell senses it and dies in a fiery inflammation, which sends out a signal to bring new cells into the zone of inflammation, and they also fall prey to the same abortive death,” Greene told Healthline. “It's a vicious cycle."
The process is called “pyroptosis,” with “pyro” meaning “fire.” Greene explained that the body's natural protective responses actually lead to a “grist mill” that chews up CD4 cells. “The resting cells now detect the DNA as foreign DNA and basically say, 'Oh my goodness, I need to die to protect the host from this foreign invader that I am now detecting in my cytpolasm.'"
The process leads to inflammation, tissue destruction, and the progression of AIDS.
A New 'One-Two Punch' AIDS Medication?
Dr. Michael Horberg, director of HIV/AIDS for Kaiser Permanente and immediate past president of the HIV Medicine Association, called Greene's research "elegant" and said he is excited for what it means to his patients. Despite modern-day antiretroviral therapy, or ART, many patients—as many as 25 percent—still progress to a CD4 count of below of 200, he said.
Researchers have identified the sensor that alerts the cell to self-destruct via pyroptosis as IF116. A drug to turn off that sensor has already been tested in clinical trials and proven safe for humans, according to Greene. It is called a capsase inhibitor and was created to treat seizures. It has not proven very effective for that use, however.
Still, Greene said that the fact it was proven well-tolerated for treating seizures over a six-week period will speed up the process of testing it for use in fighting HIV. Combined with traditional antiretroviral therapy, it could pack the one-two punch scientists long have been looking for.