Focus on the Flu

Type A is the most serious of influenzas, responsible for widespread pandemics, but type B influenza can also exert a heavy hand during the fall and winter months, accounting for half of the flu cases diagnosed in most years. Unfortunately, the popular antiviral treatment for type A flu, amantadine, as well as its derivative, rimantadine, doesn't work against a type B strain. Now NIAID-supported researchers Lawrence Pinto, Ph.D., and Robert A. Lamb, Ph.D., Sc.D., Northwestern University, have figured out why.
An influenza A virus is unable to do any real damage until its genetic material enters the host cell's nucleus, allowing it to make copies of itself. And it's the M2 protein, a pore-like "channel" on the surface of the virus, that allows this to happen. A flu virus's genetic material begins life securely locked up in the center of the virus. When a viral particle attaches to a host cell, it becomes surrounded by an acidic, membrane-bound bubble inside the cell. The M2 protein acts as a sort of "safecracker," allowing acid to move inside the virus, and causing the genetic material to loosen itself from other nearby parts. In addition, the bubble's acid environment causes hemagglutinin to change shape, poking a hole in the bubble. Together, these two actions allow the contents of the virus-namely, its RNA-to spill out, finding its way to the nucleus.
By binding to the M2 protein, however, amantadine plugs the channel's acid-conducting pore, keeping the genetic material locked safely away in the virus and preventing the virus from copying itself.	One section of the influenza A M2 channel protein — it takes four of these to form the channel — running through the membrane (dark purple band) of a flu virus CREDIT: L. Pinto
Drs. Pinto and Lamb have identified a protein on the B virus that, like A's M2 protein, helps move acid into the virus, unlocking the RNA from inside the virus particle. But instead of binding to amantadine, as A's M2 protein does, B's M2 protein repels the drug, explaining why amantadine doesn't work against a type B strain. With better understanding of the biology of B's M2 protein, researchers may develop new drugs that can shut down the virus the same way amantadine shuts down the type A virus. This information is based on the following article: "Influenza B Virus BM2 Protein Has Ion Channel Activity That Conducts Protons Across Membranes," in Developmental Cell. Dr. Pinto's laboratory Web page on the Northwestern University Web site