New Study By TSRI Scientists Sheds Light On Viral Clearance In Acute Hepatitis B Infection

April 30, 1999

La Jolla, CA. April 30, 1999 -- A study published in today's issue of Science by Drs. Luca G. Guidotti and Francis V. Chisari at The Scripps Research Institute (TSRI) demonstrates a new paradigm in viral immunology, namely that the immune system can cure viral infections without destroying the infected cells. Until now, scientists believed that viral clearance was due to the destruction of infected cells by cytotoxic T cells. But the article, "Viral Clearance Without Destruction of Infected Cells During Acute HBV Infection," demonstrates that nondestructive antiviral mechanisms can contribute to viral clearance by eliminating a virus from inside the cell without killing it.

According to Dr. Chisari, Professor, Department of Molecular and Experimental Medicine, and Director, General Clinical Research Center, "The immune system has evolved a defense mechanism that allows it to cure certain viral infections by instructing the infected cells to stop producing virus and to accelerate viral elimination. This appears to be a survival strategy to control infections of vital organs that would be destroyed if the only way to control the infection was to kill all of the infected cells."

Hepatitis B is one of the most common, serious infectious diseases in the world. More than 350 million people worldwide are chronic carriers of the virus (HBV) and it has infected 1-1.25 million Americans. The leading cause of liver cancer, the World Health Organization estimates that the infection leads to more than one million deaths every year. Each year approximately 300,000 people will become infected with the Hepatitis B virus. Although there is a safe and effective vaccine for the prevention of HBV, it is of no value to those already infected. While treatments are currently available for the infection, they have considerable limitations in terms of toxicity and long-term benefits.

In this study, the authors demonstrate that the DNA of the Hepatitis B virus disappears from the liver and the blood of acutely infected animals long before the onset of disease and the peak of T cell infiltration, suggesting that nondestructive antiviral mechanisms, triggered by inflammatory cytokines secreted by the first wave of inflammatory cells that enter the liver, contribute to clearance of the virus. According to Dr. Guidotti, these cytokines -- proteins that are secreted by cells of the immune system -- attach to receptors on infected cells and trigger them to purge themselves of the virus. This significant decrease in viral load reduces the number of cells that must be killed, thereby preserving the function of the organ while the virus is removed.

The scientific basis for the current study is the result of work conducted by Drs. Guidotti and Chisari over the past five years using a transgenic mouse model. In these experiments HBV replication was completely eliminated by inflammatory cytokines under conditions in which there was no injury to the liver.

Chisari commented, "If we can harness the curative function of the immune response in patients with chronic HBV, it may be possible to cure these patients. No treatments are available today either to trigger the production of cytokines or to deliver them to the livers of infected patients in sufficient quantities or in enough time for elimination. This work provides fundamental new insights into the immunological mechanisms of infection control."

The study was funded by the National Institutes of Health.

Scripps Research Institute

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to