Researchers have determined how liver cells can withstand virus attacks

The liver is the largest digestive gland and metabolic organ in the human body. It also has detoxification, immunity, and hematopoiesis. The liver is an important organ that supports almost all other organs of the body. However, the liver is also prone to many diseases, the most common being hepatitis, such as hepatitis A.

According to statistics, in 2019, there were several outbreaks of hepatitis A in the United States, including Florida, Ohio, and California. Hepatitis A is a liver disease caused by the hepatitis A virus, which occurs by eating contaminated food and water, sexual behavior and injecting drug use. Unlike hepatitis B and hepatitis C, hepatitis A infection does not cause chronic liver disease and is rarely fatal, but it can lead to debilitating symptoms and fulminant hepatitis (acute liver failure), which is usually fatal.

There are approximately 1.4 million cases of hepatitis A and approximately 114 million cases of infection (symptomatic and asymptomatic) each year worldwide. It is more common in areas of the world where sanitation is poor and safe water is insufficient. In 2015, acute hepatitis A caused 11,200 deaths. On July 28th each year, it was named World Hepatitis Day to raise awareness of viral hepatitis.

Although there is now a very effective and safe hepatitis A virus vaccine, people who are not vaccinated are still at risk of infection. And after the Hepatitis A patient recovers, he is immune to the Hepatitis A virus for life.

A study led by researchers at the University of North Carolina at Chapel Hill (UNC) and the Tokyo Metropolitan Academy of Medical Sciences (TMIMS) described how hepatocytes can fight the Hepatitis A virus.

The researchers found that a protein called IRF1 (interferon regulatory factor 1) is a major regulator of intrinsic resistance to viruses in hepatocytes. In other words, IRF1 has hepatocytes with congenital resistance to RNA virus infections such as hepatitis A, dengue fever and Zika disease.

IRF1 is the first member of the identified IRF family. IRF1 regulates the expression of a target gene by binding to an interferon-stimulated response element (ISRE) in its promoter. IRF1 stimulates innate and adaptive immune responses by activating specific target genes.

With in-depth research, the team found that if IRF1 is present in hepatocytes, it ensures that RARRES3 (retinoic acid receptor responder 3) causes cells to be hostile or restricted to hepatitis A infection. RARRES3 is a lipid-acting enzyme that catalyzes the calcium-dependent hydrolysis of acyl groups in various phosphatidylcholines (PC) and phosphatidylethanolamines (PE).

They also found that although expression of RARRES3 can prevent hepatitis A infection, it does not help liver cells fight other RNA viruses such as dengue.

In future research, this innate immunity of hepatocytes is worthwhile to research. Scientists can regulate infection through IRF1 and better understand why IRF1 stimulates certain cellular functions to prevent specific RNA viruses.

These findings were published in Nature Microbiology.

Cite this article

CUSABIO team. Researchers have determined how liver cells can withstand virus attacks.


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