New insight into the never-ending arms-race between viruses and their hosts

April 19, 2018, Centenary Institute of Cancer Medicine and Cell Biology
New insight into the never-ending arms-race between viruses and their hosts
Dr Chris Jolly. Credit: Centenary Institute of Cancer Medicine and Cell Biology

Viruses have been infecting all forms of life – from single-celled bacteria to humans – for as long as there has been life on Earth. Because of this, ancient mechanisms of virus resistance co-exist in our bodies alongside our more-recently evolved and highly sophisticated adaptive immune system.

Scientists at the Centenary Institute have gained new insight into the never-ending arms race that has been fought against viruses for hundreds of millions of years. The research has been published today in the PNAS journal.

Centenary's DNA Repair Group led by Dr. Chris Jolly have discovered that the enzyme SAMHD1 not only limits the supply of nucleotides to viruses inside , but also limits the supply of nucleotides to our own DNA synthesis enzymes inside B cells when they are responding to infection in other cells or responding to vaccination. This makes DNA repair inside the responding B cells particularly error-prone, ensuring that they rapidly accumulate mutations in their own antibody genes, accelerating the production of highly-protective antibodies.

"To proliferate and cause in any organism, viruses need basic DNA building blocks called deoxynucleotides. To minimise , cells from worms all the way to humans use an ancient enzyme called SAMHD1 to limit deoxynucleotide concentrations to a very low level. This inhibits virus replication. Suppression of deoxyucleotide levels by SAMHD1 is relaxed just sufficiently to allow our own DNA to be copied when we need to produce new cells for tissue growth or repair," says Dr. Jolly.

"As well as using SAMHJD1 and other enzymes inside cells to fight viruses, humans and most other vertebrates make antibodies that can neutralise viruses outside cells to prevent cell entry in the first place. Antibodies are made by specialised called B lymphocytes. During infections, B lymphocytes making antibodies specific for the invading virus to mutate their at extremely high rates. This uniquely modifies the structure of the antibody that each B cell makes. Competition between mutated B cells to collect particles then select for the few B cells that make improved ; the selected B become especially long-lived, giving us lifelong protection against repeat viral infection. This process of evolution on speed-dial takes just a few days."

This new insight and discovery by Dr. Jolly and his team including Dr. Eddy Thientosapol is part of ongoing research by the Centenary Institute's scientists in their quest to better understand disease and find cures for some of the most chronic conditions that impact human health globally. The DNA Repair Laboratory is part of Centenary's Immune Imaging Program headed by Professor Wolfgang Weninger.

The Centenary Institute is a world-leading independent medical research institute with more than 30 years experience and knowledge guiding our life-saving research, which is focused on three key areas: cancer, inflammation and cardiovascular disease. Our strength is in uncovering disease mechanisms and applying this knowledge to improve diagnostics and treatments for patients by understanding disease and finding cures for some of the most chronic diseases affecting today's society.

Explore further: Attacking flu viruses from two sides

More information: SAMHD1 enhances immunoglobulin hypermutation by promoting transversion mutation, PNAS April 18, 2018.

Related Stories

Attacking flu viruses from two sides

April 3, 2018

University of Zurich researchers have discovered a new way in which certain antibodies interact with the flu virus. This previously unknown form of interaction opens up new possibilities for developing better vaccines and ...

Enzyme behind immune cell response revealed

October 12, 2017

Monash University researchers have revealed the role played by an enzyme that is pivotal to the process of clearing infection in the body. Moreover, they suggest that the enzyme may be a potential target for drug development ...

How immune cells defend themselves against HIV

October 2, 2012

A team of scientists led by virologists Prof. Oliver T. Fackler and Prof. Oliver T. Keppler from Heidelberg University Hospital have decoded a mechanism used by the human immune system to protect itself from HIV viruses. ...

Immune response to HIV virus linked to cancer mutations

October 25, 2017

"Our findings could change the way we treat cancer," said microbiology professor Linda Chelico. Her research, funded by the federal agency NSERC, was recently published in Nucleic Acids Research and a related project was ...

Recommended for you

How quinoa plants shed excess salt and thrive in saline soils

September 21, 2018

Barely heard of a couple of years ago, quinoa today is common on European supermarket shelves. The hardy plant thrives even in saline soils. Researchers from the University of Würzburg have now determined how the plant gets ...

Basking sharks can jump as high and as fast as great whites

September 20, 2018

A collaborative team of marine biologists has discovered that basking sharks, hundreds of which are found off the shores of Ireland, Cornwall, the Isle of Man and Scotland, can jump as fast and as high out of the water as ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.