Amino acid 226 in HA of H9N2 of Flu determines cell tropism and replication in human

[sharon sanders]

Amino Acid 226 in the Hemagglutinin of H9N2 Influenza Viruses Determines Cell Tropism and Replication in Human Airway Epithelial Cells<sup>

</sup>

<nobr>Hongquan Wan</nobr> and <nobr>Daniel R. Perez^*</nobr> Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, 8075 Greenmead Drive, College Park, Maryland 20742
Received 21 December 2006/ Accepted 1 March 2007
<!-- ABS --> Influenza A viruses of the H9N2 subtype are endemic in poultryin many Eurasian countries and have occasionally caused clinicalrespiratory diseases in humans. While some avian H9N2 viruseshave glutamine (Q) at amino acid position 226 of the hemagglutinin(HA) receptor-binding site, an increasing number of isolateshave leucine (L) at this position, which has been associatedwith the establishment of stable lineages of the H2 and H3 subtypesof viruses in humans. Little is known about the importance ofthis molecular trait in the infection of H9N2 viruses in humans.We show here that during the course of a single cycle of infectionin human airway epithelial (HAE) cells cultured in vitro, theL-226-containing H9N2 viruses displayed human virus-like celltropisms (preferentially infecting nonciliated cells) differentfrom the tropisms showed by Q-226-containing H9N2 isolates (whichinfect both ciliated and nonciliated cells at ratios of 1:1to 3:2) or other waterfowl viruses (which preferentially infectciliated cells). During multiple cycles of replication in HAEcultures, L-226-containing H9N2 isolates grew consistently moreefficiently and reached approximately 100-fold-higher peak titersthan those containing Q-226, although peak titers were significantlylower than those induced by human H3N2 viruses. Our resultssuggest that the variation in residue 226 in the HA affectsboth cell tropism and replication of H9N2 viruses in HAE cellsand may have implications for the abilities of these virusesto infect humans.

<hr align="left" width="50%"><!-- null -->* Corresponding author. Mailing address: Department of Veterinary Medicine, University of Maryland, College Park, 8075 Greenmead Drive, College Park, MD 20742. Phone: (301) 314-6811. Fax: (301) 314-2593. E-mail: dperez1@umd.edu

http://jvi.asm.org/cgi/content/abstract/81/10/5181

 

[gsgs]

Re: Amino acid 226 in HA of H9N2 of Flu determines cell tropism and replication in hu

Re: Amino acid 226 in HA of H9N2 of Flu determines cell tropism and replication in hu

hmm, I remember when Webster said last year he were also concerned
about H9N2, which could/might cause the next pandemic.
At that time that gave me some relief - indicating that the H5N1-threat
wasn't as bad as he had suggested in his ABC-interview.

A H9N2 pandemic would probably be mild, I assume.
The few human cases so far were mild.
But then, the first wave in 1918 was also mild ...

Reminds me also to the RBD-study study last year, "Scripps",

they tested other choices of amino-pairs at the RBD.
Time for a followup.
I feel, that we hear these things only almost randomly - when
someone decides to publish something. While usually they
are discussing these issues behind our back.
Well, if at least they would tell us then how serious they
consider the pandemic threat , those who are better informed than us...