N Engl J Med. Pandemic Influenza Viruses ? Hoping for the Road Not Taken

[Giuseppe]

[Source: The New England Journal of Medicine, full free access text: (LINK). Extract.]

Perspective

Pandemic Influenza Viruses ? Hoping for the Road Not Taken

David M. Morens, M.D., Jeffery K. Taubenberger, M.D., Ph.D., and Anthony S. Fauci, M.D.

June 5, 2013 - DOI: 10.1056/NEJMp1307009


In the Robert Frost poem ?The Road Not Taken,? a traveler recalls a time when his forest path forked and wonders where he would have ended up had he chosen the other path. Some viruses encounter analogous evolutionary divergence points, and they may not all take linear paths to inevitable outcomes. For instance, a novel avian influenza A (H7N9) virus has emerged in China. Because all known pandemic and other human, mammalian, and poultry influenza A viruses have descended from wild-bird viruses, it seems logical that any avian influenza A virus that becomes pandemic must have serially acquired signature mutations known to be associated with circulation in humans. It would follow that mutations distinguishing ?avian-like? from ?human-like? viruses must be milestones on a fixed evolutionary pathway to potential pandemicity, including mutations affecting the hemagglutinin (HA) receptor?binding domain associated with efficient binding to human epithelial cells, polymerase mutations associated with efficient replication in human cells, and others. The fact that H7N9 isolates have some of these mutations has led to predictions of its evolution toward pandemicity.

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[gsgs]

Re: N Engl J Med. Pandemic Influenza Viruses ? Hoping for the Road Not Taken

page 1, column 2
wouldn't it be more worrying if H7N9 had _not_ these human-like
mutations ?
Then there would be danger that it might acquire them ...
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page 1,column 2
the acquisition of these mutations in pandemic strains happened in
the 1957,1968 pandemics --> "pathway"
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page 1 column 3
not every virus developes these mutations when it replicates in humans.
H5N1 usually not. pH1N1 has no E627K yet
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page 2, column 2
one reason that avian viruses in humans are so rare is the rare
exposure of humans to mallards and the even rarer opportunity
of coinfection.
> daily exposure of millions of humans to various avian influenza viruses
there are barriers, the initial load must be high, nutrition,immunity,
humidity,time of day, other viruses+bacteria,host genetics
And it must compete, may be confused with seasonal flu.
Despite lots of exposures, we only have rare human H5N1.
Exposure to mallards should be much rarer than to poultry.
Most HA,NA combinations are in waterfowl, poultry mainly
have only 5-10
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> only H1,H2,H3 could cause pandemics in history
but things have changed, we have the high concentration of
poultry and pigs only since some decades
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>all 8 segments in 1918 encode proteins close to the avian
> consensus
there is no such consensus in HA and NA (?)
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page 3, column 1
>relative protection in 1918 of >65
I would see that protection in people > ~28 years, that's
where the age-curve begins to fall. People aged 35 were
less likely to die than people aged 25. That's already
unusual for influenza and independent of the >65 folks.
And the -presumably- same virus lost that "feature" in the following
years, the age-structure in deaths in the 4th wave in 1920 was
almost back to normal.
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> a related virus was cirulating after the 1830 pandemic (5)
(almost ?)pandemics in 1836/7 , 1847/8
these could have been new strains, reassortments
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>road not taken
this is science, not poetry (IMO)