Highly pathogenic avian influenza viruses (HPAIVs) A(H5N6) were concurrently introduced into several distant regions of Japan in November 2016. These viruses were classified into the genetic clade 2.3.4.4c and were genetically closely related to H5N6 HPAIVs recently isolated in South Korea and China. In addition, these HPAIVs showed further antigenic drift.

The nucleoprotein (NP) possesses regions that are highly conserved among influenza A viruses, and has therefore been one of the target viral proteins for development of a universal influenza vaccine. It has been expected that human or humanized antibodies will be made available for the prophylaxis, pre-emptive and acute treatment of viral infection. However, it is still unclear whether anti-NP human antibody can confer protection against influenza virus infection. In this study, we generated transgenic mice expressing anti-NP human mAbs derived from lymphocytes of a patient infected with H5N1 highly pathogenic avian influenza (HPAI) virus, and experimental infections were conducted to examine antiviral effects of the anti-NP antibodies against H5N1 HPAI viral infections with a high fatality rate in mammals. Transgenic mouse lines expressing the anti-NP human mAbs at more than 1 mg ml-1 showed marked resistance to H5N1 virus infections. In addition, resistance to infection with an H1N1 subtype that shows strong pathogenicity to mice was also confirmed. Although the anti-NP mAbs expressed in the transgenic mice did not neutralize the virus, the mAbs could bind to NP located on the surface of infected cells. These results suggested a possibility that the non-neutralizing anti-NP human mAbs could induce indirect antiviral effects, such as antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity. Taken together, these results demonstrated that anti-NP human mAbs play an important role in heterosubtypic protection against lethal influenza virus infections in vivo.

Since 2014, clade 2.3.4.4 H5 subtype highly pathogenic avian influenza viruses (HPAIVs) have been distributed worldwide. These viruses, which were reported to be highly virulent in chickens by intravenous inoculation, have a consensus HPAI motif PLRERRRKR at the HA cleavage site. However, two-clade 2.3.4.4 H5N8 viruses which we isolated from wild migratory birds in late 2014 in Japan possessed atypical HA cleavage sequences. A swan isolate, Tottori/C6, had a novel polybasic cleavage sequence, PLGERRRKR, and another isolate from a dead mandarin duck, Gifu/01, had a heterogeneous mixture of consensus PLRERRRKR and variant PLRERRRRKR sequences. The polybasic HA cleavage site is the prime virulence determinant of AIVs. Therefore, in the present study, we examined the pathogenicity of these H5N8 isolates in chickens by intravenous inoculation. When 10 EID of these viruses were intravenously inoculated into chickens, the mean death time associated with Tottori/C6 was substantially longer (>6.1 days) than that associated with Gifu/01 (2.5 days). These viruses had comparable abilities to replicate in tissue culture cells in the presence and absence of exogenous trypsin, but the growth of Tottori/C6 was hampered. These results indicate that the novel cleavage motif of Tottori/C6 did not directly affect the infectivity of the virus, but Tottori/C6 caused attenuated pathogenicity in chickens because of hampered replication efficiency. It is important to test for the emergence of diversified HPAIVs, because introduction of HPAIVs with a lower virulence like Tottori/C6 might hinder early detection of affected birds in poultry farms.

23In Vietnam, numerous surveillance programs are conducted to monitor the 24 prevalence of avian influenza (AI) viruses. Three serological methods-the 25 agar-gel immunodiffusion test, hemagglutination inhibition (HI) test, and 26 enzyme-linked immunosorbent assay-are well established for detection of 27 AI virus antibodies in poultry sera. Several recent reports have validated egg 28 yolk as an alternative source for detection of AI virus antibodies. In this 29 study, we investigated AI virus antibodies in ducks by HI testing using egg 30

An iodine-doped activated carbon (named IodAC) was developed by adsorbing molecular iodine (I2) on commercially available activated carbon (AC). Iodine was selected with the purpose to add its well-known antibacterial and antiviral properties to the AC and in order to produce an innovative material for environmental pathogens control and for healthcare-related applications. The impregnation method achieved the goal of strongly adsorbing iodine on the AC surface, since both volatility and water solubility resulted to be negligible, and therefore it did not affect the stability of the material. An antibacterial test (on Escherichia coli) and an antiviral test (on an avian influenza strain) were conducted, showing the effectiveness of IodAC against the pathogens. In addition, IodAC was also compared to slaked lime (a material widely used for disinfection of outdoor spaces and livestock farming areas). The data proved the performance of IodAC against virus and bacteria and also evidenced a more stable and long-lasting disinfecting power of IodAC compared to slaked lime, the later reacting with carbon dioxide and suffering a gradually decrease of its disinfectant power; such drawback does not affect IodAC. Overall, the presented results show that IodAC can be used for a wide range of applications, including as a granular disinfectant for public spaces, for water disinfection, zoonotic diseases countermeasures (e.g., as an animal feed additive for avian influenza control), post-harvest food storage, and sanitization. Its characteristics also indicate its potential to be used for medical treatments, such as for blood, intestinal (for HIV, sepsis, irritable syndrome, ulcerative colitis therapy), and medical supplies (antibacterial bandages, gauze, cotton, etc.) sterilization.