Gene Might Hold a Clue for Why HIV Progresses in Some But Not Others

Oct 1, 2012 | Robyn Correll Carlyle | Research & Policy

UC San Diego researchers have discovered that a gene found in some human cells can inhibit HIV from replicating – perhaps shedding light on why some people with HIV progress to AIDS more rapidly than others.

The study was published in the online advance copy of the journal Nature on September 23.

The gene showed a previously unknown mechanism within the body’s immune system that reduces the virus’ ability to replicate. Known as Human Schlafen 11, the gene blocks the infected human cell from synthesizing HIV proteins. 

“Some people with HIV develop AIDS rapidly and others can be HIV positive for decades and never really develop any symptoms of the disease,” said UC San Diego Biology Professor Michael David, who led the research team.

While it’s not clear why that is, David said that genetic variations could account for the difference in susceptibility to the virus. Human cells that express Schlafen 11 have fewer HIV virus-like particles than cells that don’t have the gene.  

Schlafen 11 is part of a family of genes found in both mice and humans that is induced when an infection prompts the body to release anti-viral proteins called interferons. While the Schlafen genes have been known for years (scientists discovered the first in 1998), David said, this is the first time researchers have been able to see what the genes do at the molecular level.

David’s laboratory worked for eight years to identify what part Schlafen 11 played in human cells before uncovering its unique role. The discovery was prompted when a project scientist found the gene was missing from a cell line used in labs to produce large quantities of viruses.

“When we put Schlafen 11 back into the cell line, we got over 90 percent inhibition of virus output,” David said, confirming the gene’s ability to inhibit viral replication.

The researchers are working with scientists to examine DNA samples from thousands of people with HIV to see whether variations in the genetic sequences of Schlafen 11 are correlated with disease progression. If so, the research could lead to diagnostic tests that inform infected individuals how likely it would be that they will develop AIDS, or even treatment options that could prevent an HIV infection from ever progressing into AIDS.

If it’s possible for human cells to block viral programs without affecting their own protein synthesis, then “it’s possible that at some point a drug can do that, too,” David said.

“But our discovery is just the tip of the iceberg. There’s a lot more work to be done. Whether this will have diagnostic or therapeutic value remains to be seen.”

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