February 19, 2007

How T-Cell Leukemia Viruses Evade the Body’s Defenses

Black and white electron micrograph showing two circular viruses in the center and, to the right, the edge of the larger cell they have just left Two HTLV-1 particles, center, just after their release from an infected T cell (to the right).

Our bodies defend us in many different ways. In addition to our immune systems, our very cells have defense mechanisms to restrict infection by viruses. One mechanism is to make proteins that attach to virus particles and prevent the viruses from infecting other cells. Now, scientists from NIH’s National Cancer Institute (NCI) have discovered how one type of cancer-causing virus evades this defense strategy. The finding may eventually lead to new strategies for preventing some types of cancer.

Human T-cell leukemia virus type 1 (HTLV-1) infects about 20 million people worldwide. An active infection leads to T-cell leukemia in up to 5% of all cases. Like HIV-1, the virus that causes AIDS, HTLV-1 is a type of virus called a retrovirus. Both viruses infect immune system cells called T lymphocytes, which orchestrate the immune system's response to infected or malignant cells.

When viruses infect a cell, they make many copies of their genetic material and package them into new virus particles, which then go on to infect other cells. T lymphocyte cells produce a defensive protein called APOBEC3G, or A3G. When A3G gets packaged into virus particles, it prevents the viruses from successfully infecting other cells.

HIV-1 deals with A3G by producing a protein to destroy it. But HTLV-1 doesn't have a similar protein, so researchers didn't know how it was evading A3G. Dr. David Derse and his colleagues in the HIV Drug Resistance Program at NCI's Center for Cancer Research set out to discover the key to HTLV-1's survival.

The researchers reported in the online February 5, 2007, edition of the Proceedings of the National Academy of Sciences that altering the virus nucleocapsid protein, one of the virus's core proteins, led to more A3G being incorporated into virus particles. This, in turn, made the viruses more susceptible to A3G. HTLV-1, it seems, evades A3G by preventing it from being packaged into virus particles.

Researchers still don't understand how A3G gets packaged into virus particles. Figuring that out will be key to developing new strategies to combat HTLV-1. Current therapies for HTLV-1-associated leukemia focus on the cancer rather than on the virus, but it may be possible to prevent this leukemia by enhancing the cell's defense mechanisms or interfering with viral resistance early in infection. Similar strategies for combating HIV-1 are also being studied.

"Our ultimate goal is to try to find a way to block the virus from being active in the body,” Derse said, “but before we can do that, we must have a better understanding of how the virus evades the natural defenses in the cell that should be fighting off infection.”

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