`Survival gene` may be key to controlling HIV and hepatitis

Melbourne: A newly discovered gene that is essential for embryo survival could also hold the key to treating and potentially controlling chronic infections such as HIV, hepatitis and tuberculosis, scientists say.

The gene, called Arih2, is fundamental to the function of the immune system - making critical decisions about whether to switch on the immune response to an infection.
Its discovery has implications for the treatment of chronic overwhelming infections, such as Human immunodeficiency virus (HIV), that `exhaust` and switch off the immune system, as well as for chronic inflammatory (also known as autoimmune) conditions such as rheumatoid arthritis and sepsis, said researchers from Walter and Eliza Hall Institute in Australia and the University of Toronto, Canada.

Researcher Dr Marc Pellegrini said that Arih2 is found in dendritic cells, the sentinels of the immune system that play an essential role in raising the alarm about the presence of foreign invaders in the body.

"Arih2 is responsible for the most fundamental and important decision that the immune system has to make - whether the immune response should be initiated and progressed or whether it should be switched off to avoid the development of chronic inflammation or autoimmunity," he said.

"If the wrong decision is made, the organism will either succumb to the infection, or succumb to autoimmunity," Pellegrini said in a statement.

He explained that although our immune system works well against many infections, some organisms have developed mechanisms to evade or counteract the immune system, allowing them to persist in the body.
"During evolution, some organisms have evolved ways of exhausting our immune system to the point where the immune system just switches off, and this is what happens in HIV, hepatitis B and tuberculosis," he said.
"These organisms counter the immune response - exhausting T cells which are stimulated over and over again by the infection and becoming exhausted or paralysed. With this current discovery, what we should be able to do is circumvent these mechanisms and reinvigorate the immune response temporarily to boost the immune system and help clear these infections," he said.
Researcher Dr Greg Ebert said the team was now looking at the effect on the immune response of switching off Arih2 for short periods of time during chronic infections.

"We are investigating how manipulating Arih2 and associated pathways promotes immunity in chronic overwhelming infections, where we know the immune response is inadequate," Ebert said.

Pellegrini said it would take many years to translate the discovery to a drug that could be used in humans.

The study was published in the journal Nature Immunology.


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