Cattle are major reservoirs of the provisionally named influenza D virus, which is potentially involved in the bovine respiratory disease complex. Here, we conducted a serological survey for the influenza D virus in Japan, using archived bovine serum samples collected during 2010–2016 from several herds of apparently healthy cattle in various regions of the country. We found sero-positive cattle across all years and in all the prefectural regions tested, with a total positivity rate of 30.5%, although the positivity rates varied among regions (13.5–50.0%). There was no significant difference in positivity rates for Holstein and Japanese Black cattle. Positivity rates tended to increase with cattle age. The herds were clearly divided into two groups: those with a high positive rate and those with a low (or no) positive rate, indicating that horizontal transmission of the virus occurs readily within a herd. These data demonstrate that bovine influenza D viruses have been in circulation for at least 5 years countrywide, emphasizing its ubiquitous distribution in the cattle population of Japan.

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.

Orthomyxo- and bunyaviruses steal the 5′ cap portion of host RNAs to prime their own transcription in a process called “cap snatching.” We report that RNA modification of the cap portion by host 2′-O-ribose methyltransferase 1 (MTr1) is essential for the initiation of influenza A and B virus replication, but not for other cap-snatching viruses. We identified with in silico compound screening and functional analysis a derivative of a natural product from Streptomyces , called trifluoromethyl-tubercidin (TFMT), that inhibits MTr1 through interaction at its S -adenosyl- l -methionine binding pocket to restrict influenza virus replication. Mechanistically, TFMT impairs the association of host cap RNAs with the viral polymerase basic protein 2 subunit in human lung explants and in vivo in mice. TFMT acts synergistically with approved anti-influenza drugs.

A total of 3,045 environmental samples and oropharyngeal and cloacal swabs from apparently healthy poultry have been collected at three live bird markets (LBMs) at which practices were applied to reduce avian influenza (AI) virus transmission (intervention LBMs) and six conventional LBMs (non-intervention LBMs) in Thua Thien Hue province in 2014 to evaluate the efficacy of the intervention LBMs. The 178 AI viruses, including H3 (19 viruses), H4 (2), H5 (8), H6 (30), H9 (114), and H11 (5), were isolated from domestic ducks, muscovy ducks, chickens, and the environment. The prevalence of AI viruses in intervention LBMs (6.1%; 95% CI: 5.0-7.5) was similar to that in non-intervention LBMs (5.6%; 95% CI: 4.5-6.8; χ(2)=0.532; df=1; P=0.53) in the study area. Eight H5N6 highly pathogenic avian influenza (HPAI) viruses were isolated from apparently healthy ducks, muscovy ducks, and an environmental sample in an intervention LBM. The hemagglutinin genes of the H5N6 HPAI viruses belonged to the genetic clade 2.3.4.4, and the antigenicity of the H5N6 HPAI viruses differed from the H5N1 HPAI viruses previously circulating in Vietnam. Phylogenetic and antigenic analyses of the H6 and H9 viruses isolated in both types of LBMs revealed that they were closely related to the viruses isolated from domestic birds in China, Group II of H6 viruses and Y280 lineage of H9 viruses. These results indicate that the interventions currently applied in LBMs are insufficient to control AI. A risk analysis should be conducted to identify the key factors contributing to AI virus prevalence in intervention LBMs.