HIV cure 'likely lies in targeting dormant virus reserves'

Date: Feb-02-2015 HIV inserts itself directly into the DNA of our immune cells. AIDS develops

when the virus hijacks cell machinery and replicates itself, gradually weakening

our immunity. Anti-HIV therapy interrupts the hijacking but does not touch intact

virus that remains dormant. Now, a new study shows how lurking pools of dormant HIV

may hold the secret to curing the disease.

HIV belongs to a family of viruses that insert themselves directly into the DNA of their host cells.

The researchers, led by a team from Rockefeller University, New York, NY, report

their findings in the journal Cell.

HIV belongs to a family of viruses that insert themselves directly into the

host's genome.

In the case of HIV, it inserts itself into the DNA of a type of white blood cell

called CD4 T lymphocytes. These cells are involved in triggering immune

responses.

When HIV inserts itself into the DNA of CD4 T cells, one of two things can

happen. Either it becomes active and hijacks the cell to make copies of itself that

then invade and take over other cells (and this eventually kills the host cell); or

it lies dormant, the only sign of its presence being a tiny fragment of foreign DNA

in the cell's genome.

However, in most cases, what happens is something in-between. Some of the virus

goes on to cause infection, hijack cells and proliferate, and some of it lies

dormant. As the years go by, these dormant pools pose a persistent and growing

potential threat to a victim with a gradually weakening immune system.

Latent reservoir of HIV unlikely to be in expanded immune cell clones

As anti-HIV drugs only target the active infection - when the virus is taking

over cell machinery and making copies of itself - the dormant virus lies untouched

and continues lurking in the dormant pool, ready to wake up at any time.

First author Lillian Cohn, a graduate student in the Molecular Immunology Lab at

the Rockefeller University, says:

"If a patient stops taking antiretrovirals, the infection rebounds. It

is truly amazing that the virus can give rise to AIDS 20 years after the initial

infection."

The researchers believe the dormant pool of HIV hides out in a type of CD4 T

cell that helps the immune system remember particular pathogens. When they meet a

pathogen they have come across before, they trigger production of clone T cells

tuned to recognize it. Previous studies have suggested this clonal expansion is how HIV

maintains its latent reservoir.

But, as Cohn explains, their study found the latent reservoir is unlikely to be

in the clones:

"It has recently been shown that infected white blood cells can proliferate over

time, producing many clones, all containing HIV's genetic code. However, we found

that these clones do not appear to harbor the latent reservoir of virus. Instead

our analysis points to cells that have never divided as the source of the latent

reservoir."

Tests showed HIV in expanded clones could not hijack cells and replicate

Using blood samples from 13 people infected with HIV, the team sequenced the

sites in the genomes of infected cells where HIV had inserted itself.

With the help of specially designed analytical techniques, they could see if an

infected cell had previously been copied in the clonal expansion part of an immune

response: that is whether it was a cloned or unique CD4 T cell, as Cohn

explains:

"Given the size of the human genome, it is highly unlikely the virus

would insert itself in exactly the same place more than once. So, if multiple cells

contained virus with identical integration sites, we classified them as clones.

Meanwhile, if a cell had a unique integration site, one not shared with any other

cell, then we assumed that cell was unique."

Altogether, the team tested 75 viral sequences they found in the expanded clones

to see if they had the potential to go on to the hijacking stage and produce more

virus. None could, so they concluded it was highly unlikely that viable dormant

virus was lurking in cloned cells.

Meanwhile, in December 2014, Medical News Today learned of a study that

found as HIV evolves to become resistant to the host's natural immunity, this adaptation may also slow its ability to cause

AIDS.

Written by Catharine Paddock PhD

Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.