Abstract (provisional) Background
Since the first outbreak recorded in northern areas of Pakistan in early 2006, highly
pathogenic avian influenza H5N1 viruses were isolated from commercial poultry and
wild and domestic birds from different areas of Pakistan up to July 2008. Different
isolates of H5N1 were sequenced to explore the genetic diversity of these viruses.
Results
Phylogenetic analysis revealed close clustering and highest sequence identity in all
8 genes to HPAI H5N1 isolates belonging to unified H5 clade 2.2, sub-lineage EMA-3
recovered from Afghanistan during the same time period. Two subgroups with in Pakistani
H5N1 viruses, from domestic and wild birds, were observed on the basis of their sequence
homology and mutations. HPAI motif, preferred receptor specificity for alpha-(2, 3)
linkages, potential N-linked glycosylation sites and an additional glycosylation site
at the globular head of HA protein of four Pakistani H5N1 isolates. While, the amino
acids associated with sensitivities to various antiviral drugs (Oseltamivir, Zanamivir,
Amantadine) were found conserved for the Pakistani H5N1 isolates. Conspicuously, some
important mutations observed at critical positions of antigenic sites (S141P, D155S,
R162I & P181S) and at receptor binding pocket (A185T, R189K & S217P) of HA-1. A high
sequence similarity between Pakistani HP H5N1 and LP H9N2 viruses was also observed.
Avian like host specific markers with the exception of E627K in PB2, K356R in PA,
V33I in NP, I28V in M2 and L107F in NS2 proteins were also observed.
Conclusions
Various point mutations in different genes of H5 viruses from Pakistan were observed
during its circulation in the field. The outbreaks started in Khyber Pakhtoon Khawa
(North West) province in 2006 and spread to the Southern regions over a period of
time. Though migratory birds may have a role for this continued endemicity of clade
2.2 H5N1 viruses during 2006--2008 in Pakistan, the possibility of their transmission
through legal or illegal poultry trade across the borders cannot be ignored.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
http://www.virologyj.com/content/9/1/300/abstract
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