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HIV may stay hidden in ‘quiet’ immune cells

In what could lead to a cure for HIV, researchers have found that the human immunodeficiency virus may stay hidden for years in certain “quiet” immune cells.

Drugs for HIV have become adept at suppressing infection, but they still can not eliminate it because the medication in these pills does not touch the virus’ hidden reserves, which lie dormant within infected white blood cells, the researchers said.

“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 harbour the latent reservoir of virus,” said study author Lillian Cohn from Rockefeller University.

“Instead our analysis points to cells that have never divided as the source of the latent reservoir,” Cohn said.

HIV belongs to a family of viruses that insert themselves directly into the host cell’s genome where they can hide out quietly after the initial infection.

HIV mostly targets CD4 T lymphocytes, a type of T cell involved in initiating an immune response.

When HIV integrates itself into the genetic code of a CD4 T cell, it may produce an active infection, hijacking the cell to produce more copies of itself in order infect other cells, and killing it in the process. Antiretroviral drugs that suppress HIV infection work by disrupting this hijacking. But the virus may also fail to produce an active infection, remaining a quiet, tiny fragment of DNA tucked within the host cell’s genome. If so, the drugs have nothing to disrupt, and the infection remains latent.

“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,” Cohn says.

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The researchers tested 75 viral sequences taken from the expanded clones of cells to see if they had the potential to produce more of the virus. None could.

“While we 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,” Cohn 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,” Cohn said.

The reservoir of latent virus may be hiding out in a type of CD4 T cell: long-lived memory cells that help the immune system remember particular pathogens, the researchers pointed out.

The study appeared in the journal Cell.

Lillian B. Cohn, Israel T. Silva, Thiago Y. Oliveira, Rafael A. Rosales, Erica H. Parrish, Gerald H. Learn, Beatrice H. Hahn, Julie L. Czartoski, M. Juliana McElrath, Clara Lehmann, Florian Klein, Marina Caskey, Bruce D. Walker, Janet D. Siliciano, Robert F. Siliciano, Mila Jankovic, and Michel C. Nussenzweig. HIV-1 Integration Landscape during Latent and Active Infection. Cell , Volume 160 , Issue 3 , 420 – 432 DOI:10.1016/j.cell.2015.01.020

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