Highly pathogenic (HP) avian influenza viruses (AIVs) are naturally restricted to H5 and H7
subtypes with a polybasic cleavage site (CS) in hemagglutinin (HA) and any AIV with an intravenous
pathogenicity index (IVPI) 1.2. Although only a few non-H5/H7 viruses fulfill the criteria of HPAIV;
it remains unclear why these viruses did not spread in domestic birds. In 2012, a unique H4N2
virus with a polybasic CS 322PEKRRTR/G329 was isolated from quails in California which, however,
was avirulent in chickens. This is the only known non-H5/H7 virus with four basic amino acids
in the HACS. Here, we investigated the virulence of this virus in chickens after expansion of the
polybasic CS by substitution of T327R (322PEKRRRR/G329) or T327K (322PEKRRKR/G329) with or
without reassortment with HPAIV H5N1 and H7N7. The impact of single mutations or reassortment
on virus fitness in vitro and in vivo was studied. Ecient cell culture replication of T327R/K carrying
H4N2 viruses increased by treatment with trypsin, particularly in MDCK cells, and reassortment with
HPAIV H5N1. Replication, virus excretion and bird-to-bird transmission of H4N2 was remarkably
compromised by the CS mutations, but restored after reassortment with HPAIV H5N1, although not
with HPAIV H7N7. Viruses carrying the H4-HA with or without R327 or K327 mutations and the
other seven gene segments from HPAIV H5N1 exhibited high virulence and ecient transmission in
chickens. Together, increasing the number of basic amino acids in the H4N2 HACS was detrimental
for viral fitness particularly in vivo but compensated by reassortment with HPAIV H5N1. This may
explain the absence of non-H5/H7 HPAIV in poultry.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89484 |
| Date | 02 February 2024 |
| Creators | Gischke, Marcel, Ulrich, Reiner, Fatola, Olanrewaju I., Scheibner, David, Salaheldin, Ahmed H., Crossley, Beate, Böttcher-Friebertshäuser, Eva, Veits, Jutta, Mettenleiter, Thomas C., Abdelwhab, Elsayed M. |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2353 |
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