Evolution’s Fast Lane - The Monster at Our Door: The Global Threat of Avian Flu - page 2

mammal species. Compared to other human pathogens, it is also evolving at record-breaking speed; from
year to year its proteins change amino acids to create modified strains requiring new vaccines, a process
called antigenic drift. Moreover, every human generation or so, a bird or pig version of influenza A will
swap genes with a human type of influenza, or more drastically, acquire mutations that permit it to vault
over the species barrier. This revolutionary event is called antigenic shift, and it signals the imminence of
a pandemic. In effect, influenza A reinvents itself as a new disease against which we have no protective
immunological memory. In epidemiological parlance (and in contrast to more stable viruses like small-
pox), it is a “constantly emerging disease.” 11
To appreciate the true genius of influenza A, it is necessary to know a little about its macromolecules
and their stunning evolutionary capabilities. Like all viruses, influenza is a parasitic genome traveling in
the company of clever proteins. Under an electron microscope it is revealed to be a spheroid bristling
with tiny spikes and mushrooms, rather like an infinitesimal dandelion. The spikes consist of three inter-
twined molecules of hemagglutinin, an amazing protein that derives its name from its ability to agglu-
tinate red blood cells. The square-headed mushrooms, fewer in number, are powerful enzymes known as
neuraminidase. The outer surface of the virus also has a few M2 proteins that function as proton pumps;
these allow the virus to adjust the relative acidity of its interior. Inside the virus's lipid jacket—stolen
from a host cell—is its strange genome. All living cells, of course, are programmed by the instructions
contained in their DNA double helices. Influenza's genetic software, however, consists of single-stranded
RNA packaged in eight separate segments known as ribonucleoprotein complexes (RNPs). Inside each
of these complexes, an RNA molecule is coiled tightly around a nucleoprotein and bound together with
the polymerases required for its synthesis. Inside the host, the virus also produces a nonstructural pro-
tein (NS1) which interferes with the cellular interferon-based immune response. Finally, a matrix protein
called M1 fills the remaining space, cushioning the RNPs like so much styrofoam popcorn.
This highly competent little assembly is chemically inert until the hemagglutinin spikes make contact
with appropriate receptors (actually sialic acid residues) on the surface of certain cells. While hemagglu-
tinin (hence: HA) is the molecular key that influenza uses to unlock and enter host cells, different key con-
figurations are needed to open different cells. Avian influenza HA, for example, generally only unlocks
the intestinal cells of waterfowl, while human HA has been refashioned to break into cells in the mucous
lining of the respiratory system. This difference in lock and key configurations is generally considered
to be the species barrier that prevents avian influenzas from easily circulating among mammals. Recent
research has shown, however, that slight amino substitutions in avian HA—perhaps even the change of a
single glutamine to leucine—may suffice to unlock human cells. 12
Once influenza's HA has docked with a host cell, actual entry requires that the big HA molecule be
cleaved down the middle to expose key amino acid complexes; some virologists compare this to opening a
Swiss army knife. This cleavage is catalyzed by proteases, protein-hungry enzymes in the host organism.
Most influenza HAs are fussy in choosing proteases, but some are more promiscuous. The latter probably
have faster rates of attack and are correspondingly more virulent. In any case, HA's success at breaking
and entering is the sine qua non of an influenza infection, and it is the primary target (or antigen ) of im-
mune response and vaccination. Pandemic influenza is usually defined as the emergence or reappearance
of an HA subtype against which most people have no prior immunity.