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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. Efficient 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 efficient 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.

In Egypt, highly pathogenic avian influenza A(H5N1) clade 2.2.1 virus was introduced to poultry via migratory birds in late 2005 (1) and is now endemic among poultry in Egypt (2). [...]

The antiviral and immunostimulant effect of dietary supplementation of Spirulina platensis (SP) against Infectious bursal disease (IBD) was assessed as follows; 126 one- day-old cobb broiler chicks were randomly distributed into six groups (21 birds/group with three replicates, 7 birds each): G1 (non-vaccinated, and non-challenged ; NC), G2 (non-vaccinated, and challenged; PC), vaccinated challenged G3 (vaccinated, and challenged; VC), Spirulina 0.1% (vaccinated, 0.1% SP- supplemented, and challenged; G4), Spirulina 0.3% (vaccinated, 0.3% SP-supplemented, and challenged; G5), and Spirulina 0.5% (vaccinated, 0.5% SP-supplemented, and challenged; G6). The chicks in NC, PC, and VC groups were not supplemented with SP. All vaccinated groups, regardless SP supplementation, showed significant improvement of body weight gain (19% in 0.3% SP) and FCR during IBDv challenge (10 dpc) (P˂0.05). On the 10th dpc, IBD ELISA titer in SP-supplemented groups were decreased (P>0.05) than that of G3, suggesting an antiviral efficacy of SP. This antiviral activity was evident by the viral RNA load in the cloacal swabs as well. The viral shedding peak was on the 5th day pc which was significantly decreased on G4-6 (P˂0.05) in comparison to G2 and G3. Also, the bursal ratio was improved in SP supplemented groups. comparable to G3. Moreover, in unchallenged broilers, the gene expression of INF-γ and IL-18 were upregulated while that of IL-10 was downregulated in spleen of SP- supplemented chicks. Finally, severe histopathological lesions of kidneys, bursa, thymus, and spleen were observed in G2 which moderately minimized in G3 and were more alleviated in SP-supplemented groups. Collectively, SP supplementation improved body weight gain and decreased viral shedding with antiviral activity. The mechanisms of SP against IBDV challenge may include cell-mediated immunity promoting effect, antiviral activity, and/or anti-inflammatory effect that should be further studied. [ABSTRACT FROM AUTHOR]

Wild birds are the reservoir for low-pathogenic avian influenza viruses, which are frequently transmitted to domestic birds and occasionally to mammals. In 2014, an H10N7 virus caused severe mortality in harbor seals in northeastern Europe. Although the hemagglutinin (HA) of this virus was closely related to H10 of avian H10N4 virus, it possessed unique nonsynonymous mutations, particularly in the HA1 subunit in or adjacent to the receptor binding domain and proteolytic cleavage site. Here, the impact of these mutations on virus replication was studied in vitro. Using reverse genetics, an avian H10N4 virus was cloned, and nine recombinant viruses carrying one of eight unique mutations or the complete HA from the seal virus were rescued. Receptor binding affinity, replication in avian and mammalian cell cultures, cell-to-cell spread, and HA cleavability of these recombinant viruses were studied. Results show that wild-type recombinant H10N4 virus has high affinity to avian-type sialic acid receptors and no affinity to mammalian-type receptors. The H10N7 virus exhibits dual receptor binding affinity. Interestingly, Q220L (H10 numbering) in the rim of the receptor binding pocket increased the affinity of the H10N4 virus to mammal-type receptors and completely abolished the affinity to avian-type receptors. No remarkable differences in cell-to-cell spread or HA cleavability were observed. All viruses, including the wild-type H10N7 virus, replicated at higher levels in chicken cells than in human cells. These results indicate that H10N7 acquired adaptive mutations (e.g., Q220L) to enhance replication in mammals and retained replication efficiency in the original avian host. [ABSTRACT FROM AUTHOR]