Feline infectious peritonitis (FIP), caused by virulent feline coronavirus, is the leading infectious cause of death in cats. The type I interferon (type I IFN)-mediated immune responses provide host protection from infectious diseases. Several coronaviruses have been reported to evolve diverse strategies to evade host IFN response. However, whether feline infectious peritonitis virus (FIPV) antagonizes the type I IFN signaling remains unclear. In this study, we demonstrated that FIPV strain DF2 infection not only failed to induce interferon-β (IFN-β) and interferon-stimulated gene (ISG) production, but also inhibited Sendai virus (SEV) or polyinosinic-polycytidylic acid (poly(I:C))-induced IFN-β production. Subsequently, we found that one of the non-structural proteins encoded by the FIPV genome, nsp5, interrupted type I IFN signaling in a protease-dependent manner by cleaving the nuclear factor κB (NF-κB) essential modulator (NEMO) at three sites—glutamine132 (Q132), Q205, and Q231. Further investigation revealed that the cleavage products of NEMO lost the ability to activate the IFN-β promoter. Mechanistically, the nsp5-mediated NEMO cleavage disrupted the recruitment of the TRAF family member-associated NF-κB activator (TANK) to NEMO, which reduced the phosphorylation of interferon regulatory factor 3 (IRF3), leading to the inhibition of type I IFN production. Our research provides new insights into the mechanism for FIPV to counteract host innate immune response.

Feline bocavirus (FBoV) is a newly identified bocavirus of cats in the family Parvoviridae. A novel FBoV HRB2015-LDF was first identified from the cat with severe enteritis in Northeast China, with an overall positive rate of 2.78% (1/36). Phylogenetic and homologous analysis of the complete genome showed that FBoV HRB2015-LDF was clustered into the FBoV branch and closely related to other FBoVs, with 68.7–97.5% identities. And the genes of VP1, NPA and NS1 shared 70.7–97.6, 72.4–98.6 and 67.2–98.0% nucleotide identities with other FBoVs, respectively. The results suggested that the FBoVs could be divided into two distinct lineages, and the difference of nucleotide identities was >20–30% between the lineages.

Feline calicivirus (FCV) causes upper respiratory tract diseases and even death in cats, thereby acting as a great threat to feline animals. Currently, FCV prevention is mainly achieved through vaccination, but the effectiveness of vaccination is limited. In this study, 105 FCV strain VP1 sequences with clear backgrounds were downloaded from the NCBI and subjected to a maximum likelihood method for systematic evolutionary analysis. Based on the genetic analysis results, FCV-positive sera were prepared using SPF mice and Chinese field cats as target animals, followed by a cross-neutralization assay conducted on the different genotype strains and in vivo challenge tests were carried out to further verify with the strain with best cross-protection effect. The results revealed that FCV was mainly divided into two genotypes: GI and GII. The GI genotype strains are prevalent worldwide, but all GII genotype strains were isolated from Asia, indicating a clear geographical feature. This may form resistance to FCV prevention in Asia. The in vitro neutralization assay conducted using murine serum demonstrated that the cross-protection effect varied among strains. A strain with broad-spectrum neutralization properties, DL39, was screened. This strain could produce neutralizing titers (10 × 2^3.08–10 × 2^0.25) against all strains used in this study. The antibody titers against the GI strains were 10 × 2^3.08–10 × 2^0.5 and those against the GII strains were 10 × 2^0.75–10 × 2^0.25. Preliminary evidence suggested that the antibody titer of the DL39 strain against GI was higher than that against GII. Subsequent cross-neutralization assays with cat serum prepared with the DL39 strain and each strain simultaneously yielded results similar to those described above. In vivo challenge tests revealed that the DL39 strain-immunized cats outperformed the positive controls in all measures. The results of several trials demonstrated that strain DL39 can potentially be used as a vaccine strain. The study attempted to combine the genetic diversity and phylogenetic analysis of FCV with the discovery of potential vaccines, which is crucial for developing highly effective FCV vaccines.

In response to viral infection, host cells activate various antiviral responses to inhibit virus replication. While feline herpesvirus 1 (FHV-1) manipulates the host early innate immune response in many different ways, the host could activate the antiviral response to counteract it through some unknown mechanisms. MicroRNAs (miRNAs) which serve as a class of regulatory factors in the host, participate in the regulation of the host innate immune response against virus infection. In this study, we found that the expression levels of miR-26a were significantly upregulated upon FHV-1 infection. Furthermore, FHV-1 infection induced the expression of miR-26a via a cGAS-dependent pathway, and knockdown of cellular cGAS significantly blocked the expression of miR-26a induced by poly (dA:dT) or FHV-1 infection. Next, we investigated the biological function of miR-26a during viral infection. miR-26a was able to increase the phosphorylation of STAT1 and promote type I IFN signaling, thus inhibiting viral replication. The mechanism study showed that miR-26a directly targeted host SOCS5. Knockdown of SOCS5 increased the phosphorylation of STAT1 and enhanced the type I IFN-mediated antiviral response, and overexpression of suppressor of the cytokine signalling 5 (SOCS5) decreased the phosphorylation of STAT1 and inhibited the type I IFN-mediated antiviral response. Meanwhile, with the knockdown of SOCS5, the upregulated expression of phosphorylated STAT1 and the anti-virus effect induced by miR-26a were significantly inhibited. Taken together, our data demonstrated a new strategy of host miRNAs against FHV-1 infection by enhancing IFN antiviral signaling.