XiaoEr LianHuaQinqGan alleviates viral pneumonia in mice infected by influenza A and respiratory syncytial viruses

AbstractContext Xiaoer lianhuaqinqgan (XELH), developed based on Lianhua Qingwen (LHQW) prescription, contains 13 traditional Chinese medicines. It has completed the investigational new drug application to treat respiratory viral infections in children in China.Objective This study demonstrates the pharmacological effects of XELH against viral pneumonia.Materials and methods The antiviral and anti-inflammatory effects of XELH were investigated in vitro using H3N2-infected A549 and LPS-stimulated RAW264.7 cells and in vivo using BALB/c mice models of influenza A virus (H3N2) and respiratory syncytial virus (RSV)-infection. Mice were divided into 7 groups (n = 20): Control, Model, LHQW (0.5 g/kg), XELH-low (2 g/kg), XELH-medium (4 g/kg), XELH-high (8 g/kg), and positive drug (20 mg/kg oseltamivir or 60 mg/kg ribavirin) groups. The anti-inflammatory effects of XELH were tested in a rat model of LPS-induced fever and a mouse model of xylene-induced ear edoema.Results In vitro, XELH inhibited the pro-inflammatory cytokines and replication of H1N1, H3N2, H1N1, FluB, H9N2, H6N2, H7N3, RSV, and HCoV-229E viruses, with (IC50 47.4, 114, 79, 250, 99.2, 170, 79, 62.5, and 93 μg/mL, respectively). In vivo, XELH reduced weight loss and lung index, inhibited viral replication and macrophage M1 polarization, ameliorated lung damage, decreased inflammatory cell infiltration and pro-inflammatory cytokines expression in lung tissues, and increased the CD4+/CD8+ ratio. XELH inhibited LPS-induced fever in rats and xylene-induced ear edoema in mice.Conclusion XELH efficacy partially depends on integrated immunoregulatory effects. XELH is a promising therapeutic option against childhood respiratory viral infections

Pathogenicity and immunogenicity of gI/gE/TK-gene-deleted Felid herpesvirus 1 variants in cats

Abstract Background Felid herpesvirus 1 (FHV-1) is a major pathogenic agent of upper respiratory tract infections and eye damage in felines worldwide. Current FHV-1 vaccines offer limited protection of short duration, and therefore, do not reduce the development of clinical signs or the latency of FHV-1. Methods To address these shortcomings, we constructed FHV ∆gIgE-eGFP, FHV ∆TK mCherry, and FHV ∆gIgE/TK eGFP-mCherry deletion mutants (ΔgI/gE, ΔTK, and ΔgIgE/TK, respectively) using the clustered regularly interspaced palindromic repeats (CRISPR)/CRISP-associated protein 9 (Cas9) system (CRISPR/Cas9), which showed safety and immunogenicity in vitro. We evaluated the safety and efficacy of the deletion mutants administered with intranasal (IN) and IN + subcutaneous (SC) vaccination protocols. Cats in the vaccination group were vaccinated twice at a 4-week interval, and all cats were challenged with infection 3 weeks after the last vaccination. The cats were assessed for clinical signs, nasal shedding, and virus-neutralizing antibodies (VN), and with postmortem histological testing. Results Vaccination with the gI/gE-deleted and gI/gE/TK-deleted mutants was safe and resulted in significantly lower clinical disease scores, fewer pathological changes, and less nasal virus shedding after infection. All three mutants induced virus-neutralizing antibodies after immunization. Conclusions In conclusion, this study demonstrates the advantages of FHV-1 deletion mutants in preventing FHV-1 infection in cats