Chuck Bednar for redOrbit.com – Your Universe Online
While new treatments have proven successful at suppressing HIV infection, they have thus far been unable to eliminate it due to the fact that they cannot attack the virus as it hides dormant in the cells of a person’s immune system.
New research published last Thursday in the journal Cell is aiming to change that, however, by helping to identify which types of cells probably harbor latent HIV and which ones probably do not. The authors of the study believe their work could help find a cure for the virus.
“It has recently been shown that infected white blood cells can proliferate over time, producing many clones, all containing HIV’s genetic code,” explained study author Lillian Cohn, a graduate student at the Rockefeller University Laboratory of Molecular Immunology.
“However, we found that these clones do not appear to harbor the latent reservoir of virus,” she added. Instead, Cohn said that she and her colleagues found that cells that have never divided are likely the primary source of latent HIV.
The pathogen belongs to a family of viruses which insert themselves directly into the genome of the host cells, the researchers explained. Once there, they can hide largely undetected following the initial infection. HIV targets primarily CD4 T lymphocytes, a type of cell that helps initiate an immune response, by integrating itself into their genetic code.
By hijacking these cells, HIV is able to self-replicate in order to infect other cells, killing it in the process. Antiretroviral drugs that suppress the infection disrupt this process. However, the virus may not necessarily produce an active infection, opting instead to stay hidden within the genome. As a result, there is no process for the drug to disrupt, allowing the infection to remain latent.
Typically, however, what really happens is something in the middle: the virus manages to invade some of the T cell’s genome, but issues with the process prevent it from completely taking over the cell and replicating itself. The few fully-successful integrations that take place, however, still do damage to a person’s immune system and leaves him or her susceptible to diseases.
“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,” Cohn explained. Her team believes that the latent HIV virus may be hiding away in one type of CD4 T cell – a long-lived memory cell which helps a patient’s immune system remember specific types of pathogens.
When these T cells come in contact with a disease-causing agent it has previously encounters, they trigger the immune response designed to recognize it, a process known as clonal expansion. Previous studies have indicated that this process is vital to maintaining HIV’s latent reservoir.
Cohn and her co-authors analyzed cloned and unique CD4 T cells in blood samples from 13 HIV-infected individuals, using a special analytical computational technique which allowed them to identify sites where HIV had become integrated into individual cells.
“Given the size of the human genome, it is highly unlikely the virus would insert itself in exactly the same place more than once,” said Cohn. “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.”
They tested 75 viral sequences obtained from the expanded clones of cells to see if they had the potential to produce more of the virus, and found that none of them could. While Cohn explained that they “cannot rule out the possibility that a rare clone of cells may contain an active virus, it appears most likely that latent reservoir – and the potential target for therapies meant to cure HIV – resides in the more rare single cells containing unique integrations.”
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