Oral Supplementation of the Vitamin D Metabolite 25(OH)D3 Against Influenza Virus Infection in Mice.

Vitamin D is a fat-soluble vitamin that is metabolized by the liver into 25-hydroxyvitamin D [25(OH)D] and then by the kidney into 1,25-dihydroxyvitamin D [1,25(OH)2D], which activates the vitamin D receptor expressed in various cells, including immune cells, for an overall immunostimulatory effect. Here, to investigate whether oral supplementation of 25-hydroxyvitamin D3 [25(OH)D3], a major form of vitamin D metabolite 25(OH)D, has a prophylactic effect on influenza A virus infection, mice were fed a diet containing a high dose of 25(OH)D3 and were challenged with the influenza virus. In the lungs of 25(OH)D3-fed mice, the viral titers were significantly lower than in the lungs of standardly fed mice. Additionally, the proinflammatory cytokines IL-5 and IFN-γ were significantly downregulated after viral infection in 25(OH)D3-fed mice, while anti-inflammatory cytokines were not significantly upregulated. These results indicate that 25(OH)D3 suppresses the production of inflammatory cytokines and reduces virus replication and clinical manifestations of influenza virus infection in a mouse model.

A Novel Combination of Prion Strain Co-Occurrence in Patients with Sporadic Creutzfeldt-Jakob Disease.

Six subgroups of sporadic Creutzfeldt-Jakob disease have been identified by distinctive clinicopathologic features, genotype at polymorphic codon 129 [methionine (M)/valine (V)] of the PRNP gene, and type of abnormal prion proteins (type 1 or 2). In addition to the pure subgroups, mixed neuropathologic features and the coexistence of two types of abnormal prion proteins in the same patient also have been reported. Here, we found that a portion of the patients previously diagnosed as MM1 had neuropathologic characteristics of the MM2 thalamic form (ie, neuronal loss of the inferior olivary nucleus of the medulla). Furthermore, coexistence of biochemical features of the MM2 thalamic form also was confirmed in the identified cases. In addition, in transmission experiments using prion protein-humanized mice, the brain material from the identified case showed weak infectivity and generated characteristic abnormal prion proteins in the inoculated mice resembling those after inoculation with brain material of MM2 thalamic form. Taken together, these results show that the co-occurrence of MM1 and MM2 thalamic form is a novel entity of sporadic Creutzfeldt-Jakob disease prion strain co-occurrence. The present study raises the possibility that the co-occurrence of the MM2 thalamic form might have been overlooked so far because of the scarcity of abnormal prion protein accumulation and restricted neuropathology.

Potency of an inactivated avian influenza vaccine prepared from a non-pathogenic H5N1 reassortant virus generated between isolates from migratory ducks in Asia.

A reassortant influenza virus, A/duck/Hokkaido/Vac-1/2004 (H5N1) (Dk/Vac-1/04), was generated between non-pathogenic avian influenza viruses isolated from migratory ducks in Asia. Dk/Vac-1/04 (H5N1) virus particles propagated in embryonated chicken eggs were inactivated with formalin and adjuvanted with mineral oil to form a water-in-oil emulsion. The resulting vaccine was injected intramuscularly into chickens. The chickens were challenged with either of the highly pathogenic avian influenza virus strains A/chicken/Yamaguchi/7/2004 (H5N1) or A/swan/Mongolia/3/2005 (H5N1) at 21 days post-vaccination (p. v.), when the geometric mean serum HI titers of the birds was 64 with the challenge virus strains. The vaccinated chickens were protected from manifestation of disease signs upon challenge with either of the highly pathogenic avian influenza viruses. However, challenge virus was recovered at low titers from the birds at 2 and 4 days post-challenge (p.c.). All 3 chickens challenged at 6 days p.v. died, whereas 3 chickens challenged at 8 days p.v. survived. These results indicate that the present vaccine confers clinical protection and reduction of virus shedding against highly pathogenic avian influenza virus challenge and should be useful as an optional tool in emergency cases.