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Feline infectious peritonitis (FIP) is a lethal disease caused by a pathogenic coronavirus, feline infectious peritonitis virus (FIPV), in cats. Effective vaccines have been unsuccessful due to the frequent mutation of FIPV and antibody-dependent enhancement (ADE) caused by vaccine-induced IgG antibodies (Abs). This study examined the induction of pan-coronavirus IgM Ab in mice and its ameliorating effects in feline FIP using CoV-mMAP8, an octavalent dendrimer composed of multiple antigenic peptides. The 11-amino acid peptide (SAIEDLLFNKV) was designed as the highly conserved region of the fusion peptide at the N-terminus of S2’ subunit of the spike protein found in human and animal coronaviruses and was then conjugated to an octavalent dendrimer to form CoV-mMAP8. After a total of three injections of CoV-mMAP8 into Balb/c mice with α-galactosylceramide (α-GC) co-administered in the second injection, serum titers of IgM Abs increased against the peptide, recombinant spike proteins of SARS-CoV-2 and MERS-CoV, and crude viral antigens of canine coronavirus, porcine endemic diarrhea virus, and FIPV. In contrast, serum titers of IgG Abs did not significantly increase against any antigens. When CoV-mMAP8 was injected into three cats experimentally infected with FIPV, hyperthermia was improved within seven days after the injection with ameliorating inflammatory markers such as the platelet-to-lymphocyte ratio and the systemic immune-inflammatory index. One cat that showed recurrent hyperthermia received an additional injection of CoV-mMAP8, and clinical improvement was observed again. Postmortem examinations confirmed chronic lesions of FIP in all the cats, providing evidence that FIPV had been successfully infected and treated with CoV-mMAP8 in all the cats. Based on the induction of pan-coronavirus IgM Abs in mice and ameliorating effects in FIP of cats, it is assumed that CoV-mMAP8 has the potential to overcome the challenges posed by variants and ADE in FIPV. The mutational compatibility of CoV-mMAP8 can make it a viable universal vaccine for various coronaviruses beyond FIPV.

IntroductionSevere fever with thrombocytopenia syndrome (SFTS) is a fatal viral disease characterized by high fever, thrombocytopenia, leukopenia, and multi-organ haemorrhage. Disruption of the humoral immune response and decreased lymphocyte numbers are thought to contribute to the disease severity. These findings have been obtained through the analysis of peripheral blood leukocytes in human patients, whereas analysis of lymph nodes has been limited. Thus, in this study, we characterized the germinal centre response and apoptosis in the lymph nodes of cats with fatal SFTS, because SFTS in cats well mimics the pathology of human SFTS.MethodsLymph node tissue sections collected during necropsy from seven fatal SFTS patients and five non-SFTS cases were used for histopathological analysis. Additionally, lymph node tissue sections collected from cats with experimental infection of SFTS virus (SFTSV) were also analysed.ResultsIn the lymphoid follicles of cats with SFTS, a drastic decrease in Bcl6- and Ki67-positive germinal centre B cells was observed. Together, the number of T cells in the follicles was also decreased in SFTS cases. In the paracortex, a marked increase in cleaved-caspase3 positivity was observed in T cells. These changes were independent of the number of local SFTS virus-positive cell. Furthermore, the analysis of cats with experimental SFTSV infection revealed that the intrafollicular Bcl6- and CD3-positive cell numbers in cats with low anti-SFTSV antibody production were significantly lower than those in cats with high anti-SFTSV antibody production.DiscussionThese results suggest that dysfunction of the humoral response in severe SFTS was caused by the loss of germinal centre formation and massive apoptosis of T cells in the lymph nodes due to systemically circulating viruses.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tickborne infectious disease caused by SFTS virus (SFTSV). We report 7 cases of spontaneous fatal SFTS in felines. Necropsies revealed characteristic lesions, including necrotizing lymphadenitis in 5 cases and necrotizing splenitis and SFTSV-positive blastic lymphocytes in all cases. We detected hemorrhagic lesions in the gastrointestinal tract in 6 cases and lungs in 3 cases, suggesting a more severe clinical course of SFTS in felids than in humans. We noted necrotic or ulcerative foci in the gastrointestinal tract in 3 cases, the lung in 2 cases, and the liver in 4 cases. We clarified that blastic lymphocytes are predominant targets of SFTSV and involved in induction of necrotic foci. We also found that thymic epithelial cells were additional targets of SFTSV. These results provide insights for diagnosing feline SFTS during pathological examination and demonstrate the similarity of feline and human SFTS cases.

Feline leukemia virus (FeLV) is an exogenous retrovirus that causes malignant hematopoietic disorders in domestic cats, and its virulence may be closely associated with viral sequences. FeLV is classified into several subgroups, including A, B, C, D, E, and T, based on viral receptor interference properties or receptor usage. However, the transmission manner and disease specificity of the recombinant viruses FeLV-D and FeLV-B remain unclear. The aim of this study was to understand recombination events between exogenous and endogenous retroviruses within a host and elucidate the emergence and transmission of recombinant viruses. We observed multiple recombination events involving endogenous retroviruses (ERVs) in FeLV from a family of domestic cats kept in one house; two of these cats (ON-T and ON-C) presented with lymphoma and leukemia, respectively. Clonal integration of FeLV-D was observed in the ON-T case, suggesting an association with FeLV-D pathogenesis. Notably, the receptor usage of FeLV-B observed in ON-T was mediated by feline Pit1 and feline Pit2, whereas only feline Pit1 was used in ON-C. Furthermore, XR-FeLV, a recombinant FeLV containing an unrelated sequence referred to the X-region, which is homologous to a portion of the 5′-leader sequence of Felis catus endogenous gammaretrovirus 4 (FcERV-gamma4), was isolated. Genetic analysis suggested that most recombinant viruses occurred de novo; however, the possibility of FeLV-B transmission was also recognized in the family. This study demonstrated the occurrence of multiple recombination events between exogenous and endogenous retroviruses in domestic cats, highlighting the contribution of ERVs to pathogenic recombinant viruses. IMPORTANCE Feline leukemia virus subgroup A (FeLV-A) is primarily transmitted among cats. During viral transmission, genetic changes in the viral genome lead to the emergence of novel FeLV subgroups or variants with altered virulence. We isolated three FeLV subgroups (A, B, and D) and XR-FeLV from two cats and identified multiple recombination events in feline endogenous retroviruses (ERVs), such as enFeLV, ERV-DC, and FcERV-gamma4, which are present in the cat genome. This study highlights the pathogenic contribution of ERVs in the emergence of FeLV-B, FeLV-D, and XR-FeLV in a feline population. [ABSTRACT FROM AUTHOR]