"This is how HIV decides to become active"

Researchers have found the molecular mechanism underpinning HIV's decision to remain in an active or dormant state. This may lead to new therapies that work by keeping the virus in a permanently dormant state.
The study, led by a team from the Gladstone Institutes in San Francisco, CA, features in a paper now published in the journal Cell.
The findings may also explain cell fate decisions that occur elsewhere in biology — such as how stem cells decide whether to remain as stem cells or differentiate into specialized cells, including brain or heart cells, when they divide.

Senior study author Prof. Leor S. Weinberger, the director of the Center for Cell Circuitry at the Gladstone Institutes, likens the process to how we "hedge our bets" when we make decisions about financial investments.

To "protect against volatility in the market," we may choose to place some funds in high-risk stocks with potentially high yields and the rest in low-risk, low-yield options.

"Similarly," he explains, "HIV covers its bases in a volatile environment by generating both active and dormant infections."

HIV latent reservoir

Once it enters the human body, HIV inserts its genetic material into the DNA of the "host" immune cells. Doing this enables HIV to force the cell's machinery to make copies of the virus.
However, some HIV-infected immune cells go into a dormant, or latent, state and won't make new virus. HIV can hide in this "latent reservoir" for a long time.
Current HIV treatments are highly effective at reducing the amount of active virus in the body. However, they are not so good at tackling dormant HIV, which can reactivate as soon as treatment stops. This is one of the main reasons that we cannot yet cure HIV.
In previous work, Prof. Weinberger and his colleagues showed that HIV latency "is not an accident" but a deliberate "survival tactic."
The tactic is "evolutionarily advantageous for the virus" because in the sites where HIV first enters the body, there are not many immune cells for it to invade, and if it killed them all by being fully active, there would not be any left to carry on the infection.

HIV exploits 'gene expression noise'

By putting some of the cells that it invades into a latent state, HIV ensures that activation can wait until those cells have been carried into tissue where there are many more target cells, thereby ensuring a higher chance of survival and ongoing infection.
The team found that HIV is able to generate an active or a dormant state by taking advantage of a normal phenomenon inside cells that is called "random fluctuations in gene expression."
Because of random fluctuations in gene expression, which scientists also call "noise," two cells with exactly the same genetic makeup can produce different amounts of the same protein. The difference can be enough to influence cell "function and fate."HIV expresses its genes inside the host cell using a mechanism called "alternative splicing," which enables it to slice up its genetic material and assemble it in a variety of arrangements.

Source : Medical News Today