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Clade 2.3.4.4 H5Nx subtype avian influenza viruses (AIVs) have circulated in poultry and wild birds worldwide. Recently, an increasing number of H5Nx human infection cases have been reported occurred. Live attenuated influenza vaccines demonstrate more advantages than other types of vaccines, such as ease of administration, elicitation of systemic immune responses, and the ability to generate breadth protection. However, the attenuated viruses also bear the risk of reassortment with the wild-type influenza A virus. To overcome this reassortment problem, we designed and constructed Clade 2.3.4.4 H5 chimeric cold-adapted attenuated influenza vaccines (CAIVs) by introducing the hemagglutinin ectodomains of H5N6 into a cold-adapted attenuated master donor of an influenza B virus. These H5 CAIVs induce humoral antibody response, mucosal immune response, and cellular immune response in mice models. After two doses were administered in mice, H5 CAIVs provided cross-protection responses with 100% survival against wild-type Clade 2.3.4.4 H5 subtype AIVs. The immunized mice exhibited more significant reductions of lung viral titers or lung pathology than those in the mock group mice. In ferret models, Clade 2.3.4.4b and 2.3.4.4h H5 CAIVs produced a cross-protective efficacy against wild-type Clade 2.3.4.4b and Clade 2.3.4.4h H5 AIVs. The findings of the current study indicate that our H5 CAIVs may have the potential to prevent and control H5Nx influenza viruses in humans. [ABSTRACT FROM AUTHOR]

Coronaviruses are commonly characterized by a unique discontinuous RNA transcriptional synthesis strategy guided by transcription-regulating sequences (TRSs). However, the details of RNA synthesis in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been fully elucidated. Here, we present a timescaled, gene-comparable transcriptome of SARS-CoV-2, demonstrating that ACGAAC functions as a core TRS guiding the discontinuous RNA synthesis of SARS-CoV-2 from a holistic perspective. During infection, viral transcription, rather than genome replication, dominates all viral RNA synthesis activities. The most highly expressed viral gene is the nucleocapsid gene, followed by ORF7 and ORF3 genes, while the envelope gene shows the lowest expression. Host transcription dysregulation keeps exacerbating after viral RNA synthesis reaches a maximum. The most enriched host pathways are metabolism related. Two of them (cholesterol and valine metabolism) affect viral replication in reverse. Furthermore, the activation of numerous cytokines emerges before large-scale viral RNA synthesis. IMPORTANCE SARS-CoV-2 is responsible for the current severe global health emergency that began at the end of 2019. Although the universal transcriptional strategies of coronaviruses are preliminarily understood, the details of RNA synthesis, especially the timematched transcription level of each SARS-CoV-2 gene and the principles of subgenomic mRNA synthesis, are not clear. The coterminal subgenomic mRNAs of SARS-CoV-2 present obstacles in identifying the expression of most genes by PCR-based methods, which are exacerbated by the lack of related antibodies. Moreover, SARS-CoV-2-related metabolic imbalance and cytokine storm are receiving increasing attention from both clinical and mechanistic perspectives. Our transcriptomic research provides information on both viral RNA synthesis and host responses, in which the transcription-regulating sequences and transcription levels of viral genes are demonstrated, and the metabolic dysregulation and cytokine levels identified at the host cellular level support the development of novel medical treatment strategies. [ABSTRACT FROM AUTHOR]