Re: H7N9 ?Discussion
Re: H7N9 ?Discussion
I mean, in humans.
Fouchier said in a recent interview it increased virulence
1000 fold in ferrets (or mice) afair
searching ...
http://vir.sgmjournals.org/content/88/2/547.full
[equine H7N7] ... with PB2-E627K increasing virulence by 1000-fold as measured by MLD50 [in mice]
How-
ever, from the accumulated data, we conclude that none of the
tested mutations in PB2 had a major impact on the virulence of
A/Netherlands/602/2009 in mice and ferrets. Certainly, for
E627K and D701N, this was in contrast to our expectations,
because a large impact of these mutations was observed in the
context of other influenza viruses in mice and ferrets. In mice
infected with HPAI A/Netherlands/219/2003 (H7N7) virus,
PB2 E627K was the main determinant of pathogenicity, related
to ?1,000-fold differences in lung virus titers (21). Adaptation
of A/Equine/London/1416/73 (H7N7) to mice resulted, among
others, in an E627K substitution in PB2, leading to 1,000-fold-
increased virulence of the virus as measured by the dose lethal
to 50% of infected mice (MLD50) (26). The PB2 E627K mu-
tation was also the main determinant of differences in patho-
genicity of 1997 HPAI H5N1 viruses, in which the MLD50
changed ?1,000-fold upon introduction of the mutation (11).
In HPAI H5N1 viruses isolated from ducks in China, D701N
was the main determinant of pathogenesis in the mouse model
(15). The pathogenicity of a variant of A/seal/Massachusetts/
1/1980 (H7N7) that is highly pathogenic to mice, SC35, was
also determined in part by D701N in PB2 (8). Thus, the mouse
model seems appropriate for testing the effects of both E627K
and D701N in PB2, yet in the context of A/Netherlands/602/
2009 (S-OIV), there was no such marked effect of these mu-
tations on pathogenesis.
There was no major effect
on pathogenesis and transmission of A/Netherlands/602/2009
from any of the three PB2 mutations tested in ferrets
jvi.asm.org/content/84/8/3752.full.pdf
