Mutated HIV Proviruses Are Not as Harmless as Previously Thought

When it comes to HIV, a virus that continues to plague a staggering 36.7 million individuals worldwide, researchers from around the globe have long set their sights on a goal that seems to have remained just beyond their reach: finding a cure.

Now, research from Johns Hopkins School of Medicine and George Washington School of Medicine has supplied another piece to the puzzle. Although proteins created by defective forms of HIV cannot necessarily produce “functional infectious HIV,” they are not all harmless contrary to previous belief. These proteins can actually distract the immune system from fighting off the “functional virus.”

A specific subset of defective HIV proviruses, referred to as “hypermutated” HIV proviruses, creates “faulty proteins,” which the scientists believe are still recognized by cytotoxic T-lymphocytes, the immune cells tasked with identifying and destroying functional HIV.

These faulty proteins can cause a lot of trouble when it comes to immune response. According to the press release issued by Johns Hopkins, they can:

• Make it difficult to accurately measure a patient’s viral load
• Exhaust immune systems
• Shield functional HIV from attack by natural means or drugs
• Seriously complicate the development of a cure

“The virus has a lot of ways, even in its defective forms, to distract our immune systems, and understanding how they do this is essential to finding a cure,” lead study investigator Ya Chi Ho, MD, PhD, instructor of medicine at the Johns Hopkins School of Medicine, explained in the press release.

For their study, the scientists looked at six HIV-positive individuals, from whom they collected “nine different defective HIV proviruses.” They then “transfected cultures of human immune cells with them in the laboratory.” The scientists grew the transfected cells and tested them for any telltale markers of HIV production, such as RNA and proteins. Their findings were a little unsettling—even though they were mutated, all the proviruses were still able to produce markers of proliferation.

“The fact that defective proviruses can contribute to viral RNA and protein production is concerning, because it means that the measurements of HIV load in infected patients may not be as accurate as we thought,” said Dr. Ho. “Part of the count is coming from defective viruses.”

Upon proving that the defective proviruses could create HIV proteins, the researchers proceeded to investigate whether human immune cells were able to “biologically recognize and interact with those proteins.” To do this, the scientists transfected cells with 6 different types of defective HIV provirus collected from patients. Dr. Ho and his team partnered up with co-first author of the study R. Brad Jones, PhD, assistant professor of microbiology, immunology, and tropical medicine at the George Washington School of Medicine and Health Sciences, to match cytotoxic T-cells “from the corresponding patients to the infected cells.” They found that, indeed, an infected patient’s T-cells can recognize the cells containing “hypermutated HIV.”

So, what does this mean? Since the proteins created by the defective proviruses are recognized by the T-cells responsible for attacking normal HIV, they are also capable of distracting them from eliminating functional HIV. “The cytotoxic T-lymphocytes’ ability to identify and target the real threat appears to be greatly impaired, because they may attack proteins from defective proviruses instead of the real thing,” Dr. Ho explained.

However, not all hope is lost.

“If we identify and find a way to use the right protein, perhaps one of those expressed by the ‘hypermutated’ HIV we found in this study, we could create a potent vaccine which could boost the immune system enough to eliminate HIV altogether,” said Dr. Ho.

Information is powerful in this fight, according to Dr. Ho—the more that is known about these defective proviruses, the closer scientists will be to winning the fight against HIV, once and for all.