MICROBIOLOGY AND IMMUNOLOGY ON-LINE |
From the National Institute of Allergy and Infectious Diseases
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 by letting acid enter the virus particle to "loosen up" the
virus's genetic material.
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.
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.