One
way to fight diseases including HIV infection and autoimmune disorders could
involve changing how a naturally occurring enzyme called SAMHD1 works to
influence the immune system, new research suggests.
The study, led by researchers from The Ohio State
University, details how the enzyme influences proteins that stimulate the
immune response.
SAMHD1 isn't a molecular "good guy" or
"bad guy" per se, but there are cases in which blocking its activity
might thwart disease progression, said Li Wu, the study's senior author and a
professor of veterinary biosciences and microbial infection and immunity in
Ohio State's Center for Retrovirus Research.
The research, conducted in human and mouse immune cells,
appears online in the journal Proceedings of the National Academy of Sciences.
"Lacking this enzyme due to SAMHD1 gene mutations
can activate the human immune system and increase inflammation, and now we
better understand the fundamental biological process behind that," Wu
said.
"In a perfect world, SAMHD1 is responsible for
balanced regulation of the immune response, but it also could limit HIV or
other viral infections and alter the progression and treatment of certain
cancers. We need good immune responses, obviously, but we don't want
overwhelming immune activation."
Before this study, it was unclear whether and how SAMHD1
regulated immune responses, Wu said. Scientists identified the human gene for
this enzyme in 2000, and since then it's been linked to human diseases
including autoimmune disorders, HIV infection and cancers.
Unlocking the precise way in which it influences disease
progression is one of the goals of Wu's lab. Previous research had established
SAMHD1 as a key player in inhibiting HIV replication in human immune cells,
piquing his interest.
The new study illuminated the way in which SAMHD1
interacts with several cellular proteins that play a critical role in
regulating innate immune responses. Importantly, the enzyme can act as an
inhibitor of potentially harmful responses during viral infection.
"The enzyme's job is to break down a DNA building
block in our cells- to act as 'molecular scissors,'" Wu said.
"Too much of this building block due to SAMHD1
deficiency caused by genetic mutations can lead to autoimmune diseases and help
cancerous tumours grow. If we can find a way to cut off or reduce the supply,
the disease might not be viable -- like a car without gas."
This study could open the possibility of finding ways to
turn this activity on and off, making way for new therapeutic approaches for
hard-to-treat diseases, Wu said.
"Because inflammatory pathways influence nearly all
diseases in humans and animals, including HIV infection and cancers,
identification of SAMHD1 as an inhibitor of immunity may have far-reaching
implications in biomedical research," he said.
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participate in the conference at: https://std-hiv-aids.cmesociety.com/abstract-submission
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