In the 2016/2017 winter season in Japan, HuNoV GII.P16-GII.2 strains (2016 strains) emerged and caused large outbreaks of acute gastroenteritis. To better understand the outbreaks, we examined the molecular evolution of the VP1 gene and RdRp region in 2016 strains from patients by studying their time-scale evolutionary phylogeny, positive/negative selection, conformational epitopes, and phylodynamics. The time-scale phylogeny suggested that the common ancestors of the 2016 strains VP1 gene and RdRp region diverged in 2006 and 1999, respectively, and that the 2016 strain was the progeny of a pre-2016 GII.2. The evolutionary rates of the VP1 gene and RdRp region were around 10-3 substitutions/site/year. Amino acid substitutions (position 341) in an epitope in the P2 domain of 2016 strains were not found in pre-2016 GII.2 strains. Bayesian skyline plot analyses showed that the effective population size of the VP1 gene in GII.2 strains was almost constant for those 50 years, although the number of patients with NoV GII.2 increased in 2016. The 2016 strain may be involved in future outbreaks in Japan and elsewhere.

A novel GII.P17-GII.17 variant norovirus emerged as a major cause of norovirus outbreaks from December 2014 to March 2015 in Japan. Named Hu/GII/JP/2014/ GII.P17-GII.17, this variant has a newly identified GII. P17 type RNA-dependent RNA polymerase, while the capsid sequence displays amino acid substitutions around histo-blood group antigen (HBGA) binding sites. Several variants caused by mutations in the capsid region have previously been observed in the GII.4 genotype. Monitoring the GII.17 variant's geographical spread and evolution is important. The present study uses complete genome sequences and phylogenetic and in silico analyses to characterise GII.P17 norovirus strains contributing to gastroenteritis outbreaks in Japan from December 2014 to March 2015.

Background: Propolis has been used worldwide as a dietary supplement to maintain and improve human health. We examined whether ethanol extracts of Brazilian propolis exhibit antiviral activity against influenza virus in vitro and in vivo. Methods: Among 13 ethanol extracts screened in a plaque reduction assay, four showed anti-influenza virus activity. The anti-influenza efficacy of the four extracts was further examined in a murine influenza virus infection model. The mice were infected intranasally with influenza virus, and the four extracts were orally administered at 10 mg/kg three times daily for seven successive days after infection. Results: In this infection model, only one extract, AF-08, was significantly effective at 10 mg/kg in reducing the body weight loss of infected mice. The doses of 2 and 10 mg/ kg were also effective in prolonging the survival times of infected mice significantly, but 0.4 mg/kg was not. The antiinfluenza efficacy of AF-08 at 10 mg/kg was confirmed in a dose-dependent manner in mice. AF-08 at 10 mg/kg significantly reduced virus yields in the bronchoalveolar lavage fluids of lungs in infected mice as compared with the control. The reduction of virus yields by AF-08 at 10 mg/kg significantly corresponded to those induced by oseltamivir at 1 mg/kg twice daily from day 1 to day 4 after infection. Conclusion: The Brazilian propolis AF-08 was indicated to possess anti-influenza virus activity and to ameliorate influenza symptoms in mice. AF-08 may be a possible candidate for an anti-influenza dietary supplement for humans.

Ethanol extracts (AF-06, 07, and 08, 10 mg/kg) of Brazilian propolis were administered orally to cutaneously herpes simplex virus type 1 (HSV-1)-infected mice three times daily on days 0 to 6 after infection to evaluate their efficacies against HSV-1 infection and significantly limited development of herpetic skin lesions. AF-07 and 08 significantly reduced virus titers in brain and/or skin on day 4 without toxicity, but AF-08 had no anti-HSV-1 activity in vitro. AF-06 and 08 significantly enhanced delayed-type hypersensitivity (DTH) to inactivated HSV-1 antigen in infected mice. Oral AF-08-administration significantly augmented interferon (IFN)-γ production by HSV-1 antigen from splenocytes of HSV-1-infected mice, while direct exposure of splenocytes of infected mice to AF-06 significantly elevated IFN-γ production in vitro. Thus, AF-08 might have components that are active in vivo even after oral administration and those of AF-06 might be active only in vitro. Because DTH is a major host defense for intradermal HSV-1 infection, augmentation of DTH response by AF-06 or 08, directly or indirectly, respectively, may contribute to their efficacies against HSV-1 infection. In addition, AF-06 and 07 possibly contain anti-HSV-1 components contributing to their efficacies. Such biological activities of Brazilian propolis may be useful to analyze its pharmacological actions.

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