Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lung cell patches its own DNA on the fly to survive influenza

30.07.2019

Resilient cells make lung less hospitable to viruses, but may be double-edged sword

Scientists at Duke University have identified one kind of lung cell that can hustle to repair its damaged DNA and survive an attack of the influenza A virus while other kinds of cells around it die in droves.


Duke researchers are studying one kind of lung cell that ramps up its DNA repair mechanisms to resist being killed by influenza. (Ciliated cells are green, basal cells are red, and cell nuclei are blue).

Credit: Nicholas Heaton Lab, Duke University

The finding reveals more about the battle between cells and viruses at the smallest level, and also may provide some important clues for respiratory conditions such as chronic obstructive pulmonary disease and asthma.

The resilient cell is called a club cell and it's found in the narrowest airways just above the alveoli of the lungs where gases are exchanged in the blood, said Nicholas Heaton, an assistant professor of molecular genetics and microbiology in the Duke School of Medicine. The cell's normal function is to produce surfactants and secrete various other proteins that coat the lining of the lungs. Their functions during a viral infection however, have remained incompletely understood.

Heaton and his team had found in 2014 that club cells could survive a flu infection that would kill most cells. In a 2016 study, they watched club cells crank up their protein-making machinery when under a viral assault and signal the immune system to produce high levels of pro-inflammatory molecules called cytokines.

The net result of club cell survival would be that the lungs remain somewhat hostile to new viruses even after an infection has cleared, Heaton said.

As evidence of that, he points to an intriguing clue from the 2009 influenza pandemic: The flu virus that year was actively replicating in the summer months, not its usual fall and winter months. That year another RNA-based seasonal virus, the respiratory syncytial virus (RSV), was unable to infect people at the same time that it normally would, as if the population were better able to resist it.

"It suggests that influenza makes some sort of changes that make you better able to resist another respiratory infection," Heaton said. And the club cells were probably players in this.

"We knew from previous work that club cells could survive, but we had no idea how," Heaton said.

In the latest work, appearing July 29 in Nature Microbiology, Heaton's lab, along with Sara Cherry, a colleague at the University of Pennsylvania, sorted through all of the club cell's viral response pathways during infection. They found that the club cells were ramping up DNA mismatch repair in response to infection.

An invading virus's weapon of choice is reactive oxygen, which it uses to damage any sections of DNA that are open and active within the host cell. Normally, that damage accumulates to the point that the cell can't express the genes it needs to fight off the virus, whereupon it dies.

But the club cell somehow redoubles its efforts to repair DNA damage and makes it through the infection.

To confirm that was the case, the researchers created an engineered virus that carried the necessary RNA to truly clobber all the DNA repair machinery in cultured human club cells, whereupon the club cells died from flu just like other respiratory cells.

Having patched their damaged DNA, and survived the influenza infection, club cells continue their work of producing surfactants and chemicals that encourage inflammation.

"If another virus comes in, the environment it normally comes into is pretty antiviral," Heaton said, which might explain the mystery of the missing respiratory syncytial virus in 2009.

But the survival of club cells is a two-edged sword, Heaton said. While a proinflammatory environment helps control virus levels, it's actually the over-activity of inflammation that can kill influenza patients, often after they've cleared the flu virus. The club cells that survive and stay active might actually contribute to this.

"Now we have a population of cells we know are going to be hyperinflammatory on the back side of an infection," Heaton said. "When we deplete club cells, there's less inflammation," which might be an important insight to addressing chronic obstructive pulmonary disease or asthma, Heaton said.

This research was supported by the National Institutes of Health, the Burroughs Wellcome Fund and Duke University. Duke has filed a provisional patent application for targeting DNA mismatch repair as a way to grow influenza vaccine strains in the lab.

###

CITATIONS: "DNA Mismatch Repair is Required for the Host Innate Response and Controls Cellular Fate After Influenza Virus Infection," Benjamin Chambers, Brook Heaton, Keiko Rausch, Rebekah Dumm, Jennifer Hamilton, Sara Cherry, Nicholas Heaton. Nature Microbiology, July 29, 2019. DOI: 10.1038/s41564-019-0509-3

"Club Cells Surviving Influenza A Virus Infection Induce Temporary Nonspecific Antiviral Immunity," Jennifer Hamilton, David Sachs, Jean Lim, Ryan Langlois, Peter Palese, Nicholas Heaton. Proceedings of the National Academy of Sciences, March 21, 2016. DOI: 10.1073/pnas.1522376113

"Long-Term Survival of Influenza Virus Infected Club Cells Drives Immunopathology," Nicholas S. Heaton, Ryan A. Langlois, David Sachs, Jean K. Lim, Peter Palese, and Benjamin R. tenOever. Journal of Experimental Medicine, Aug. 18, 2014. DOI: 10.1084/jem.20140488

Media Contact

Karl Leif Bates
karl.bates@duke.edu
919-448-8109

 @DukeU

http://www.duke.edu 

Karl Leif Bates | EurekAlert!
Further information:
https://today.duke.edu/2019/07/lung-cell-patches-its-own-dna-fly-survive-influenza
http://dx.doi.org/10.1038/s41564-019-0509-3

Further reports about: DNA Influenza Virus damage damaged DNA flu virus inflammation lungs respiratory syncytial virus

More articles from Health and Medicine:

nachricht A new method of tooth repair? Scientists uncover mechanisms to inform future treatment
09.08.2019 | University of Plymouth

nachricht Take a break! Brain stimulation improves motor learning
08.08.2019 | Max-Planck-Institut für Kognitions- und Neurowissenschaften

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A miniature stretchable pump for the next generation of soft robots

Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.

Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...

Im Focus: Vehicle Emissions: New sensor technology to improve air quality in cities

Researchers at TU Graz are working together with European partners on new possibilities of measuring vehicle emissions.

Today, air pollution is one of the biggest challenges facing European cities. As part of the Horizon 2020 research project CARES (City Air Remote Emission...

Im Focus: Self healing robots that "feel pain"

Over the next three years, researchers from the Vrije Universiteit Brussel, University of Cambridge, École Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI-Paris) and Empa will be working together with the Dutch Polymer manufacturer SupraPolix on the next generation of robots: (soft) robots that ‘feel pain’ and heal themselves. The partners can count on 3 million Euro in support from the European Commission.

Soon robots will not only be found in factories and laboratories, but will be assisting us in our immediate environment. They will help us in the household, to...

Im Focus: Scientists create the world's thinnest gold

Scientists at the University of Leeds have created a new form of gold which is just two atoms thick - the thinnest unsupported gold ever created.

The researchers measured the thickness of the gold to be 0.47 nanometres - that is one million times thinner than a human finger nail. The material is regarded...

Im Focus: Study on attosecond timescale casts new light on electron dynamics in transition metals

An international team of scientists involving the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) in Hamburg has unraveled the light-induced electron-localization dynamics in transition metals at the attosecond timescale. The team investigated for the first time the many-body electron dynamics in transition metals before thermalization sets in. Their work has now appeared in Nature Physics.

The researchers from ETH Zurich (Switzerland), the MPSD (Germany), the Center for Computational Sciences of University of Tsukuba (Japan) and the Center for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

What will the digital city of the future look like? City Science Summit on 1st and 2nd October 2019 in Hamburg

12.08.2019 | Event News

 
Latest News

Working out why plants get sick

16.08.2019 | Life Sciences

Newfound superconductor material could be the 'silicon of quantum computers'

16.08.2019 | Physics and Astronomy

Stanford develops wireless sensors that stick to the skin to track our health

16.08.2019 | Medical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>