Mechanism helps explain persistence of hepatitis C virus
Researchers at the University of California, San Diego School of Medicine have identified a mechanism that explains why people with the hepatitis C virus get liver disease and why the virus is able to persist in the body for so long.
The hard-to-kill pathogen, which infects an estimated 200 million people worldwide, attacks the liver cells' energy centers – the mitochondria – dismantling the cell's innate ability to fight infection. It does this by altering cells mitochondrial dynamics.
The study, published in today's issue of the Proceedings of the National Academy of Sciences, suggests that mitochondrial operations could be a therapeutic target against hepatitis C, the leading cause of liver transplants and a major cause of liver cancer in the U.S.
"Our study tells us the story of how the hepatitis C virus causes liver disease," said Aleem Siddiqui, PhD, professor of medicine and senior author. "The virus damages mitochondria in liver cells. Cells recognize the damage and respond to it by recruiting proteins that tell the mitochondria to eliminate the damaged area, but the repair process ends up helping the virus."
Mitochondria are organelles in a cell that convert energy from food (glucose) into a form of energy that can be used by cells called adenosine triphosphate.
Specifically, the researchers discovered that the virus stimulates the production of a protein (Drp 1) that induces viral-damaged mitochondria to undergo asymmetric fragmentation. This fragmentation (fission) results in the formation of one healthy mitochondrion and one damaged or bad mitochondrion, the latter of which is quickly broken down (catabolized) and dissolved in the cell's cytoplasm.
Although the fragmentation serves to excise the damaged area from the mitochondrion, the formation of a healthy mitochondrion also helps keep the virus-infected cell alive. Moreover, the virus is able to use the mitochondrial remains (all the amino acids and lipids from the catabolized mitochondrion) to help fuel its continued replication and virulence.
"It's like the bad part of the house is demolished to the benefit of the virus," Siddiqui said.
In their experiments, the researchers showed that hepatitis C-infected cells with higher Drp 1 protein levels also produced less interferon, the body's natural immune booster. These cells were also less likely to undergo apoptosis, a process that would encourage damaged cells to essentially kill themselves.
The reverse was also observed: When the Drp 1 protein was "silenced," interferon production and apoptotic activity increased.
"Mitochondrial processes are at the center of understanding the persistence of the virus and how it flies under the radar of the body's natural immune response," he said. "The trick is to find a way to deliver a drug that could target the Drp 1 protein specifically in hepatitis C-infected liver cells, maybe through nanotechnology."
Co-authors include Seong-Jun Kim and Gulam H. Syed, Mohsin Khan and Wei-Wei Chiu Division of Infectious Diseases, UCSD; Muhammad A. Sohail, Division of Gastroenterology, UCSD; and Robert G. Gish, Hepatitis B Foundation.
This research was funded, in part, by National Institutes of Health grants AI085087, DK077704, DK08379 and T32 DK07202.
Scott LaFee | Eurek Alert!
Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)
Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
13.12.2017 | Health and Medicine
13.12.2017 | Physics and Astronomy
13.12.2017 | Life Sciences