Tuesday, July 29, 2014 2:59:54 PM
A cultured liver cancer cell infected with Hepatitis C. The virus, stained red, surrounds the blue-stained nucleus and is in the process of being reproduced by virus within the cytoplasm. Credit: Takahiro Masaki/UNC Lemon Lab
Hepatitis C virus (HCV) lingers in the human body for years, slowly damaging the liver and leading to liver diseases such as hepatitis, cirrhosis and liver cancer, which is often fatal. Research conducted at the University of North Carolina at Chapel Hill has discovered a mechanism that facilitates the virus achieving this life-long persistence. Chronic HCV infection is the leading cause of liver cancer in the United States.
"Liver cancer is one of the most important causes of cancer mortality worldwide. It's also increasing in rapidly incidence within the United States, due largely to the spread of HCV among Americans in the 60s and 70s," said Stanley M. Lemon, MD, Professor of Medicine at the UNC School of Medicine and a member of the UNC Lineberger Comprehensive Cancer Center.
In a paper published online by Nature Medicine this week, a team led by Dr. Lemon and colleague Daisuke Yamane, DVM, PhD, found that HCV has a sensor function that allows it to be regulated by the oxidative damage to cell membranes that occurs as a byproduct of its replication and the body's response to it. This slows down virus growth when oxidative membrane damage becomes too high, but allows it to resume when the membrane damage is reduced. By auto-regulating its replication in this way, the virus maintains a low profile, helping it escape detection by the immune system.
"You might consider it like a thermostat," said Dr. Lemon, "one that regulates the growth of the virus like your thermostat regulates the temperature of your house."
The reason why HCV is able to achieve life-long persistence in most individuals who become infected has never been well explained. "What we have done in this paper is to show that the replication of a wide variety of hepatitis C virus strains is uniquely regulated by oxidative stress in the liver. This is an absolutely unique attribute of hepatitis virus that sets it apart from similar viruses," said Dr. Lemon.
Oxidative stress occurs when tissue injury generates free radicals, normal biological byproducts that can cause cellular damage when present in excess amounts. This promotes to inflammation and progressive scarring within the liver, leading to further disease like cirrhosis and cancer. Lipid peroxidation occurs on membranes when there are excess free radicals, and that regulates the growth of hepatitis C virus. By reducing its replication, the virus is able to persist at low levels in the liver for years. This slows the damage to the host and helps the virus to escape the attention of the body's immune system.
This autoregulatory circuit has made HCV very difficult to study in the laboratory. The virus does not grow well in cell cultures because of oxidative stress. Dr. Lemon's team have identified mutants of the virus which have lost the ability to be regulated by lipid peroxidation, and these grow much more efficiently in the laboratory.
"That allows us to use those viruses to test anti-viral drugs and possibly also for vaccine development," said Dr. Lemon.
Explore further: Transmission of hepatitis C virus following antiviral treatment
More information: "Regulation of the hepatitis C virus RNA replicase by endogenous lipid peroxidation." Daisuke Yamane, et al. Nature Medicine (2014) DOI: 10.1038/nm.3610. Received 31 March 2014 Accepted 23 May 2014 Published online 27 July 2014
http://medicalxpress.com/news/2014-07-hepatitis-virus-persists-years.html
Recent BNTC News
- Form 8-K - Current report • Edgar (US Regulatory) • 03/08/2024 09:17:00 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 03/08/2024 09:13:15 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 03/08/2024 09:12:19 PM
- Form EFFECT - Notice of Effectiveness • Edgar (US Regulatory) • 03/06/2024 05:15:18 AM
- Form DEL AM - Delaying amendment • Edgar (US Regulatory) • 02/26/2024 02:06:56 PM
- Form S-3 - Registration statement under Securities Act of 1933 • Edgar (US Regulatory) • 02/23/2024 09:09:24 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 02/13/2024 01:15:31 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 02/13/2024 01:01:16 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 12/07/2023 09:15:54 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 11/30/2023 12:31:00 PM
- Benitec Biopharma to Participate in a Fireside Chat at the 35th Annual Piper Sandler Healthcare Conference • GlobeNewswire Inc. • 11/17/2023 01:00:00 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 11/13/2023 01:03:01 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 11/13/2023 01:00:49 PM
- Benitec Biopharma Releases First Quarter 2024 Financial Results and Provides Operational Update • GlobeNewswire Inc. • 11/13/2023 01:00:00 PM
- Form DEFA14A - Additional definitive proxy soliciting materials and Rule 14(a)(12) material • Edgar (US Regulatory) • 10/20/2023 08:31:26 PM
- Form DEF 14A - Other definitive proxy statements • Edgar (US Regulatory) • 10/20/2023 10:04:42 AM
- Form 8-K - Current report • Edgar (US Regulatory) • 10/16/2023 09:29:59 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 09/28/2023 09:19:02 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 09/21/2023 12:05:29 PM
- Form 10-K - Annual report [Section 13 and 15(d), not S-K Item 405] • Edgar (US Regulatory) • 09/21/2023 12:00:53 PM
- Benitec Biopharma Releases Full Year 2023 Financial Results and Provides Operational Update • GlobeNewswire Inc. • 09/21/2023 12:00:00 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 09/18/2023 09:26:00 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 08/14/2023 09:13:45 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 08/11/2023 08:01:00 PM
- Benitec Biopharma Inc. Announces Closing of $30 Million Underwritten Public Offering • GlobeNewswire Inc. • 08/11/2023 05:00:12 PM
Axis Technologies Group and Carbonis Forge Ahead with New Digital Carbon Credit Technology • AXTG • Apr 24, 2024 3:00 AM
North Bay Resources Announces Successful Equipment Test at Bishop Gold Mill, Inyo County, California • NBRI • Apr 23, 2024 9:41 AM
Epazz, Inc.: CryObo, Inc. solar Bitcoin operations will issue tokens • EPAZ • Apr 23, 2024 9:20 AM
Avant Technologies Launches Advanced AI Supercomputing Network and Expansive Data Solutions • AVAI • Apr 23, 2024 8:00 AM
BestGrowthStocks.com Issues Comprehensive Analysis of Triller Merger with AGBA Group Holding Limited • AGBA • Apr 22, 2024 1:00 PM
Cannabix Technologies to Present Marijuana Breathalyzer Technology at International Association for Chemical Testing (IACT) Conference in California • BLO • Apr 22, 2024 8:49 AM