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Mutated HIV Proviruses Are Not as Harmless as Previously Thought

MAY 03, 2017 | KRISTI ROSA
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.”

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