Human Schlafen 11 Gene Expression Inhibits Replication Of HIV
Researchers at UC San Diego have recently discovered the anti-viral mechanism of a particular human gene that may shed light on why some HIV patients present high viremia levels while others are doing much better. The discovery, which was detailed in the last week’s edition of Nature magazine could also explain why some HIV infected patients do not progress to AIDS and show no symptoms of disease.
Researchers at UC San Diego have discovered that a gene named Human Schlafen 11 is responsible for the production of a protein able to inhibit the replication of HIV inside host cells. The protein acts by blocking viral protein synthesis inside the infected cells.
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 Michael David, a professor of biology at UC San Diego, who headed the research team. It's still unclear why that is, but one possibility is that the genetic variations in this protein, like in many other viral restriction factors, account for the differences in the susceptibility to the virus.
Cells that lack the Human Schlafen 11 gene tend to have more HIV viral particles (can be observed as dots in the left picture) compared with cells that express the Human Schlafen 11 gene and therefore able to block viral protein synthesis.
Due to the fact that the Human Schlafen 11 gene acts by blocking HIV protein synthesis, scientists are carrying out further research programs in order to observe whether variations of this particular gene can be linked to disease progression from HIV infection to AIDS. If this link is certainly established, the discovery might be the source for a new therapeutic target that could halt the progression of HIV infection to AIDS as well as new HIV diagnostic tools and methods that may determine the risk of progression to AIDS of an infected individual.
If it's possible for the human cell to inhibit the synthesis of viral programs without affecting the synthesis of cellular proteins, it's possible that at some point a drug can do that, too, said David. 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.
The Human Schlafen 11 is a member of a 6 gene family normally found in humans and 9 gene family in laboratory mice, that are induced in cells of mammals in response to different kinds of infection. Their role is to release interferons (proteins with antiviral role). The first protein from the Sclafen family was discovered was back in 1998 by Steve Hedrick, biology professor.
David stated that he spent nearly 8 years to unravel the exact Human Sclafen 11 role in mammal cells. He also added that they were also very surprised when a co-worker named Manqing Li noticed that Human Sclafen 11 was not to be found in a cell culture used to produce large amounts of HIV virus for the lab work.
When we put Schlafen 11 back into the cell line, we got over 90 percent inhibition of virus output, David said, confirming that the gene was critical to inhibiting virus replication.
Although the Sclafen genes were known to exist for many years, David’s discovery is the first of its kind that points out its exact working mechanism at molecular level. The research team has now moved their attention to other Human Sclafen genes to investigate their anti-viral effects on viruses like the influenza virus or the virus that causes dengue fever.
The scientists are also collaborating with other researchers who supervise tissue banks that contain DNA samples taken from thousands HIV positive patients in order to establish a link between Schlafen 11 gene variation and evolution of symptoms in those patients.
Study abstract here.