Genetic Variation And Antiviral Enzymes Explain Why!
Some people have a gene which is a particular variation of APOBEC3H, which produces an antiretroviral protein that protects cells by inhibiting the replication of HIV.
There are people who are exposed, often repeatedly, with any virus, even devastating ones like Ebola and HIV, but somehow they never develop symptoms of the disease or become infected. Especially in the case of HIV, doctors have long wondered why, and now a team of researchers has found an explanation. Scientists at the University of Minnesota studying HIV-1 discovered that some people have a specific variation of the gene, APOBEC3H that produces an antiretroviral protein that inhibits the replication of HIV.
Dr. Reuben S. Harris, a professor in the department of Biochemistry, Molecular Biology and Biophysics, explained to Medical Daily – “We have seven APOBEC3 genes within the variants of human population”. Harris added “from these seven genes, only APOBEC3H varies within the human population”. APOBEC3H itself has seven variations, and if you group these into those that make unstable and those that make stable proteins, Harris said to Medical Daily, “What we found is those that are stable confer resistance to some forms of HIV.”
This important finding may pave the way and open new opportunities in finding new treatments and drugs.
Viral Infectivity Factor
Viruses are often described as the ultimate parasite that cannot sustain themselves on their own or reproduce, so they require a host. In the case of the human immunodeficiency virus, their host – of – choice is T lymphocyte cells found in the immune system. After it gains control of the molecular machinery of T-cells, the virus it duplicates itself and destroys its host. Naturally, this does a huge damage on the immune system and that is why people infected with HIV become very susceptible to any pathogen invading their bodies, including diseases like cancer.
However, this picture is somewhat simplistic. The T lymphocytes have their own defense mechanism in the form of antiretroviral proteins produced by the APOBEC3 genes. Simply said, HIV has its own counter – defense — a protein known as viral infectivity factor (Vif), which tricks T lymphocytes into destroying the APOBEC3 enzymes.
A group of researchers led by Harris and doctoral student Eric Refsland, for the current study, decided to examine this interaction closely. They hypothesized that different levels of susceptibility to HIV-1 might be closely linked to the variations in the gene that is producing this antiretroviral protein.
Harris told Medical Daily, that while testing their theory, Harris and his colleagues first came to a discovery that an HIV-1 infection increased the APOBEC3H proteins. This had to be an important part of the HIV susceptibility equation. Next, they “essentially took HIV strains”, “And we figured out what amino acids are required to counteract APOBEC3H.” This was achieved by creating mutant probes to test how important a stable protein compared to an unstable protein is going to be when fighting with an HIV infection. “This is the key,” Harris told Medical Daily. “If you can’t generate these mutants, it’s difficult to interpret the cell data.”
After creating the necessary probes, then, the research team using cells from the donors found different people with different genetic variations of APOBEC3H that produced more stable and stronger antiretroviral proteins. The researchers found, that the stable variations successfully blocked the HIV-1’s ability to replicate itself in cases where the strain of HIV contained a weak version of Vif.
Unfortunately, when the HIV-1 virus had a strong version of Vif, it didn’t matter how stable or potent the protective proteins were, they lost their battle with the infection.
Harris says, he and his colleagues hope to learn ways to stop Vif from harming the APOBEC3 enzymes. Harris stated in a press release – “One could imagine drugs that stop Vif from binding with APOBEC”. Believing this to be “a bonafide HIV killing pathway,” Harris and his co-researchers are planning to activate it on infected persons. He speculates that this approach might stop the virus from replicating and indefinitely suppress it, or it could even result in curing HIV.