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Clade 2.3.4.4 H5N8 highly pathogenic avian influenza viruses (HPAIVs) have spread worldwide. Phylogenetic analysis identified two genetic groups of the H5N8 HPAIVs in South Korea; group A evolved further into four subgroups. Here, we examined the zoonotic potential, both in vivo and in vitro, of genetically distinct subgroups of H5N8 HPAIVs isolated in South Korea. When compared with other subgroups, A/mallard/Korea/H2102/2015 (H2102) virus caused relatively severe disease in mice at high doses. In ferrets, all H5N8 viruses replicated restrictively in the respiratory tract and did not induce significant clinical signs of influenza infection. In vitro studies, all viruses displayed a hemagglutinin phenotype that was poorly adapted for infection of mammals, although the H2102 virus exhibited higher replication kinetics at 33°C than the others. Although H5N8 HPAIVs have not yet acquired all the characteristics required for adaptation to mammals, their ability to evolve continuously underscores the need for timely risk assessment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Due to increasing concerns about human infection by various H7 influenza viruses, including recent H7N9 viruses, we evaluated the genetic relationships and cross-protective efficacies of three different Eurasian H7 avian influenza viruses. Phylogenic and molecular analyses revealed that recent Eurasian H7 viruses can be separated into two different lineages, with relatively high amino acid identities within groups (94.8 to 98.8%) and low amino acid identities between groups (90.3 to 92.6%). In vivo immunization with representatives of each group revealed that while group-specific cross-reactivity was induced, cross-reactive hemagglutination inhibition (HI) titers were approximately 4-fold lower against heterologous group viruses than against homologous group viruses. Moreover, the group I (RgW109/06) vaccine protected 100% of immunized mice from various group I viruses, while only 20 to 40% of immunized mice survived lethal challenge with heterologous group II viruses and exhibited high viral titers in the lung. Moreover, while the group II (RgW478/14) vaccine also protected mice from lethal challenge with group II viruses, it failed to elicit cross-protection against group I viruses. However, it is noteworthy that vaccination with RgAnhui1/13, a virus of a sublineage of group I, cross-protected immunized mice against lethal challenge with both group I and II viruses and significantly attenuated lung viral titers. Interestingly, immune sera from RgAnhui1/13-vaccinated mice showed a broad neutralizing spectrum rather than the group-specific pattern observed with the other viruses. These results suggest that the recent human-infective H7N9 strain may be a candidate broad cross-protective vaccine for Eurasian H7 viruses. IMPORTANCE Genetic and phylogenic analyses have demonstrated that the Eurasian H7 viruses can be separated into at least two different lineages, both of which contain human-infective fatal H7 viruses, including the recent novel H7N9 viruses isolated in China since 2013. Due to the increasing concerns regarding the global public health risk posed by H7 viruses, we evaluated the genetic relationships between Eurasian H7 avian influenza viruses and the cross-protective efficacies of three different H7 viruses: W109/06 (group I), W478/14 (group II), and Anhui1/13 (a sublineage of group I). While each vaccine induced group-specific antibody responses and cross-protective efficacy, only Anhui1/13 was able to cross-protect immunized hosts against lethal challenge across groups. In fact, the Anhui1/13 virus induced not only cross-protection but also broad serum neutralizing antibody responses against both groups of viruses. This suggests that Anhui1/13-like H7N9 viruses may be viable vaccine candidates for broad protection against Eurasian H7 viruses., (Copyright © 2017 American Society for Microbiology.)

This study examined the potential for cross-species transmission of influenza viruses by comparing the genetic and pathogenic characteristics of H1 avian influenza viruses (AIVs) with different host origins in Korea. Antigenic and phylogenetic analyses of H1 AIVs circulating in Korea provided evidence of genetic similarity between viruses that infect domestic ducks and those that infect wild birds, although there was no relationship between avian and swine viruses. However, there were some relationships between swine and human viral genes. The replication and pathogenicity of the H1 viruses was assessed in chickens, domestic ducks and mice. Viral shedding in chickens was relatively high. Virus was recovered from both oropharyngeal and cloacal swabs up to 5-10 days post-inoculation. The titres of domestic duck viruses in chickens were much higher than those of wild-bird viruses. Both domestic duck and wild-bird viruses replicated poorly in domestic ducks. None of the swine viruses replicated in chickens or domestic ducks; however, six viruses showed relatively high titres in mice, regardless of host origin, and induced clinical signs such as ruffled fur, squatting and weight loss. Thus, although the phylogenetic and antigenic analyses showed no evidence of interspecies transmission between birds and swine, the results suggest that Korean H1 viruses have the potential to cause disease in mammals. Therefore, we should intensify continuous monitoring of avian H1 viruses in mammals and seek to prevent interspecies transmission., (© 2014 The Authors.)

Background:   The highly pathogenic H5N1 and H9N2 influenza viruses are endemic in many countries around the world and have caused considerable economic loss to the poultry industry. Objectives  We aimed to study whether a live attenuated H5N1 vaccine comprising internal genes from a cold-adapted H9N2 influenza virus could protect chickens from infection by both H5N1 and H9N2 viruses., Methods:   We developed a cold-adapted H9N2 vaccine virus expressing hemagglutinin and neuraminidase derived from the highly pathogenic H5N1 influenza virus using reverse genetics., Results and Conclusions:   Chickens immunized with the vaccine were protected from lethal infections with homologous and heterologous H5N1 or H9N2 influenza viruses. Specific antibody against H5N1 virus was detected up to 11 weeks after vaccination (the endpoint of this study). In vaccinated chickens, IgA and IgG antibody subtypes were induced in lung and intestinal tissue, and CD4+ and CD8+ T lymphocytes expressing interferon-gamma were induced in the splenocytes. These data suggest that a live attenuated H5N1 vaccine with cold-adapted H9N2 internal genes can protect chickens from infection with H5N1 and H9N2 influenza viruses by eliciting humoral and cellular immunity., (© 2012 Blackwell Publishing Ltd.)

Pregnant women can experience high mortality, high rates of abortion, and severe pneumonia when infected with pandemic influenza viruses. In this context, the severity of the 2009 pandemic H1N1 influenza virus compared with seasonal H1N1 influenza virus is not clear. Presently, in a mouse model of pregnancy, the 2009 pandemic H1N1 influenza virus killed up to 60% of pregnant mice and caused abortion in up to 40%, whereas a circulating seasonal H1N1 influenza virus did not cause any deaths or abortions. Higher viral titers and levels of inflammatory cytokines and chemokines such as interleukin (IL)-1α, IL-6, granulocyte colony-stimulating factor, RANTES, monocyte chemotactic protein, and KC (CXCL1), were detected in the lungs of pregnant mice infected with the 2009 pandemic H1N1 influenza virus, compared with the seasonal H1N1 influenza virus. The results of our study with pregnant mice suggest that the observed higher pathogenesis in pregnant women infected with the 2009 pandemic H1N1 influenza virus than the seasonal H1N1 influenza virus may be due to higher viral replication, elevated induction of inflammatory chemokines, and reduced progesterone.

A 2009 H1N1 influenza virus pandemic, which had its origin in swine, caused severe illness and mortality in humans. Inflammatory responses may be responsible for pathogenesis caused by infection with influenza viruses. To better understand the pathogenic mechanism, clinical signs and inflammatory responses in ferrets infected with the pandemic H1N1 were compared with those caused by seasonal H1N1 influenza virus. Ferrets infected with the 2009 pandemic H1N1 virus displayed higher body temperatures, greater reduction in body weight, and higher viral titers in the tracheae and lungs. Levels of inflammatory cytokines, including interleukin-6, interferon-alpha, and tumor necrosis factor-alpha, were higher in the lungs of ferrets infected with the 2009 pandemic H1N1. The data support the idea that increased pathogenesis caused by the 2009 pandemic H1N1 influenza virus may have been partially mediated by a higher induction of pro-inflammatory cytokines in the lungs of affected humans or animals.