BackgroundFeline morbillivirus (FmoPV) is a novel paramyxovirus found to infect domestic cats. FmoPV has been isolated in several countries in Asia and Europe and is considered to have genetic diversity. Also, it is suspected to be associated with feline renal diseases including tubulointerstitial nephritis (TIN), which affects domestic cats with a high incidence rate.ResultsTo clarify the state of FmoPV infection among domestic cats in Japan, an epidemiological survey was conducted. Twenty-one out of 100 cats were found to have serum antibodies (Ab) against FmoPV-N protein by indirect immunofluorescence assay (IF) using FmoPV-N protein-expressing HeLa cells. Twenty-two of the cats were positive for FmoPV RNA in the urine and/or renal tissues. In total, 29 cats were positive for Ab and/or viral RNA. These FmoPV-infected cats were classified into three different phases of infection: RNA+/Ab + (14 cats), RNA+/Ab- (8 cats) and RNA-/Ab + (7 cats). In immunohistochemistry (IHC), 19 out of 29 cats were positive for FmoPV-N protein in kidney tissues; however, the FmoPV-N protein was located in the inflammatory lesions with severe grade in only four out of the 19 cats. Since 15 out of 29 infected cats were positive for viral RNA and Ab, approximately half of the infected cats were persistently infected with FmoPV.ConclusionsA statistically significant difference was observed between infection of FmoPV and the presence of inflammatory changes in renal lesions, indicating a relationship between FmoPV infection and feline renal diseases. However, we could not obtain histopathological evidence of a relationship between FmoPV infection and TIN.

The method of point-group determination from convergent-beam electron diffraction patterns has been established by Buxton, Eades, Steeds & Rackham [Philos. Trans. R. Soc. London (1976), 281, 171-194]. However, Table 2 given by them is inconvenient for practical purposes, since many symmetries of the dark-field and +G dark-field patterns are not given and are left for the reader's consideration. The table is improved and completed with the help of some new symmetry symbols and illustration of symmetries. The new table makes the point-group determination easy and quick. The symmetries of the symmetrical manybeam convergent-beam electron diffraction patterns have been studied by Tinnappel [PhD Thesis (1975), Tech. Univ. Berlin l using group theory. It is shown that the graphical method used by Buxton et al. can reveal the symmetries of these patterns. A method of * Present address: Hitachi Research Laboratory, Hitachi 319-12, Japan. point-group determination which uses three types of symmetrical many-beam patterns, the hexagonal sixbeam, square four-beam and rectangular four-beam patterns, is described. This method requires only one photograph in determining most diffraction groups. This fact means that the method is more convenient and reliable than that of Buxton et al., since their method requires two or three photographs for most cases. Experimental results which verify the theoretical ones are given. The characteristic features of the symmetrical many-beam method are discussed.

Feline morbillivirus (FmoPV) has recently been identified in Hong Kong and Japan. FmoPV is considered to belong to the genus Morbillivirus, in the family Paramyxoviridae. In this study, the complete nucleotide sequences of three strains of FmoPV detected in cats in Japan were determined. Among the six genes in FmoPV; N, P/V/C, M, F, H and L, the P gene showed the highest polymorphism in the nucleotide and putative amino acid sequences among the FmoPV strains. There was no geographical association in terms of the FmoPV phylogeny; however, from extensive phylogenetic and recombination analyses, we found that one Japanese FmoPV strain, MiJP003, was a probable recombinant between two virus strains in the independent lineages found in Japan and Hong Kong, respectively. The recombination was considered to have occurred within the F and H genes. Such recombination is thought to be involved in the evolution of FmoPV.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

The domain structure of a typical antiferroelectric substance, lead zirconate, is examined in detail fori the first time by electron diffraction and electron microscopy. The 90° and 60° domain configurations can be consistently understood on the basis of the pseudo-cubic unit cell. 180° domains, which are characteristic of the antiferroelectric phase, are observed. The displacement vectors between the domains are determined as ¼[21n], ¼[21̄n] and ¼[02n] (n=0 or 2) by the α-fringe theory for off-Bragg settings. Crystal structure images of the domains reveal how the unit cells connect across the domain boundary. 90° and 180° domains are found in the intermediate phase between the antiferroelectric and the paraelectric phases. The fact that 180° domains are observed is important evidence indicating that the phase is ferroelectric.