We have identified and characterized a novel member of the ankyrin-repeat family named`molecule possessing ankyrin-repeats induced by lipopolysaccharide' (MAIL). The C-terminal portion of MAIL shared high sequence homology with the IU UB family. Intraperitoneal injection of lipopolysaccharide (LPS) into mice rapidly ( 6 0.5 h) induced MAIL mRNA in various tissues, particularly in the spleen, lymph node, and lung. Ectopically expressed MAIL was localized in the nucleus, and remarkably potentiated the LPS-induced mRNA expression and secretion of interleukin (IL)-6 in Swiss 3T3 cells. These findings indicate that MAIL is one of the nuclear IU UB proteins and an activator of IL-6 production. ß

Asian H5 highly pathogenic avian influenza viruses (HPAIVs) that possess the clade 2.3.4.4 HA gene have been identified in wild birds and poultry since late 2014 in both Europe and North America (N. America). Clade 2.3.4.4 H5 HPAIVs of the H5N8 subtype have been isolated in both regions, whereas reassortment viruses with NA N1 and N2 subtypes of the North American (N. American). avian lineage have only been identified in N. America. The HA genes of those isolates were closely related to genes of the HPAIVs that have caused massive outbreaks in poultry in Korea since January 2014. The outbreaks caused by those viruses and the genetic relatedness of their HA and NA genes are reviewed in this study. Although the illegal movement of poultry and poultry products cannot be ruled out as a cause of intercontinental and intracontinental dissemination of clade 2.3.4.4 H5 HPAIVs during the winter of 2014-2015, transmission of the viruses by infected migratory birds appears to be a more plausible mechanism for their dissemination. In particular, the involvement of migratory birds in HPAIV transmission between Asia and N. America is highly likely because of the reassortments between H5N8 HPAIV and the N. American lineage avian influenza viruses.

A highly pathogenic avian influenza virus (HPAIV) of subtype H5N8, A/chicken/Kumamoto/1-7/2014, was isolated from a Japanese chicken farm during an outbreak in April 2014. Phylogenetic analysis revealed that this virus belonged to HA clade 2.3.4.4. All eight genomic segments showed high sequence similarity to those of the H5N8 subtype HPAIVs A/broiler duck/Korea/Buan2/2014 and A/baikal teal/Korea/Donglim3/2014, which were isolated in Korea in January 2014. Intranasal experimental infection of chickens and ducks with A/chicken/Kumamoto/1-7/2014 was performed to assess the pathogenicity of the virus in chickens and the potential for waterfowl to act as a virus reservoir and carrier. A high-titer virus challenge (10(6) EID50 per animal) was lethal in chickens, but they were unaffected by lower virus doses (10(2) EID50 or 10(4) EID50 per animal). Virus challenge at all doses examined was found to result in asymptomatic infection of ducks. An HI assay revealed that A/chicken/Kumamoto/1-7/2014 possessed relatively low cross-reactivity with H5 viruses belonging to clades other than clade 2.3.4.4. These results suggest that waterfowl may be able to spread the virus even if they possess antibodies resulting from a previous infection with H5 HPAIV that was antigenically distinguishable from viruses belonging to clade 2.3.4.4.