RESUMO
Fowl adenovirus serotype 4 (FAdV-4) infections result in substantial economic losses in the poultry industry. Recent findings have revealed that FAdV-4 significantly suppresses the host immune response upon infection; however, the specific viral and host factors contributing to this immunomodulatory activity remain poorly characterized. Moreover, diverse cell types exhibit differential immune responses to FAdV-4 infection. To elucidate cell-specific host responses, we performed transcriptomic analysis of FAdV-4 infected leghorn male hepatocellular (LMH) and chicken embryo fibroblast (CEF) cells. Although FAdV-4 replicated more efficiently in LMH cells, it provoked limited interferon-stimulated gene induction. In contrast, FAdV-4 infection triggered robust antiviral responses in CEF cells, including upregulation of cytosolic DNA sensing and interferon-stimulated genes. Knockdown of key cytosolic DNA sensing molecules enhanced FAdV-4 replication in LMH cells while reducing interferon-stimulated gene expression. Our findings reveal cell-specific virus-host interactions that provide insight into FAdV-4 pathogenesis while identifying factors that mediate antiviral immunity against FAdV-4.
Assuntos
Infecções por Adenoviridae , Aviadenovirus , Galinhas , Fibroblastos , Imunidade Inata , Doenças das Aves Domésticas , Animais , Masculino , Fibroblastos/virologia , Fibroblastos/imunologia , Embrião de Galinha , Infecções por Adenoviridae/veterinária , Infecções por Adenoviridae/imunologia , Infecções por Adenoviridae/virologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/imunologia , Galinhas/imunologia , Aviadenovirus/fisiologia , Aviadenovirus/imunologia , Sorogrupo , Hepatócitos/virologia , Hepatócitos/imunologiaRESUMO
Although the influenza A virus H7N9 subtype circulates within several avian species, it can also infect humans with a severe disease outcome. To better understand the biology of the H7N9 virus we examined the host response to infection in avian and human cells. In this study we used the A/Anhui/1/2013 strain, which was isolated during the first wave of the H7N9 epidemic. The H7N9 virus-infected both human (Airway Epithelial cells) and avian (Chick Embryo Fibroblast) cells, and each infected host transcriptome was examined with bioinformatic tools and compared with other representative avian and human influenza A virus subtypes. The H7N9 virus induced higher expression changes (differentially regulated genes) in both cell lines, with more prominent changes observed in avian cells. Ortholog mapping of differentially expression genes identified significant enriched common and cell-type pathways during H7N9 infections. This data confirmed our previous findings that different influenza A virus subtypes have virus-specific replication characteristics and anti-virus signaling in human and avian cells. In addition, we reported for the first time, the new HIPPO signaling pathway in avian cells, which we hypothesized to play a vital role to maintain the antiviral state of H7N9 virus-infected avian cells. This could explain the absence of disease symptoms in avian species that tested positive for the presence of H7N9 virus.
Assuntos
Subtipo H7N9 do Vírus da Influenza A/fisiologia , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/virologia , Células A549 , Animais , Embrião de Galinha , Galinhas , Cães , Expressão Gênica , Humanos , Influenza Aviária/genética , Influenza Aviária/metabolismo , Influenza Aviária/virologia , Influenza Humana/genética , Influenza Humana/metabolismo , Influenza Humana/virologia , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/metabolismo , Transdução de SinaisRESUMO
CONTEXT: Previous studies demonstrated that sodium tanshinone IIA sulfonate (STS) could inhibit MDV replication in vitro. The mechanism about how STS inhibits MDV replication is still not well understood. OBJECTIVE: In this study, we evaluated the effect of STS on gB gene/protein of Marek's disease virus (MDV). MATERIALS AND METHODS: The concentration of 0.25 mg/ml of STS was used in this study. Meanwhile, 0.25 mg/ml of acyclovir (ACV) was used as a positive control. About 9-11-d-old embryonated specific-pathogen-free (SPF) chicken eggs were used to prepare CEF cells. CEF cells were infected with MDV 2 h, followed by treatment with STS. Real-time PCR and western blot assay were used to measure the gB (UL27) gene/protein expression in STS treatment group at 24, 48, 72, and 96 h post-infection. RESULTS: Compared with MDV control, the gB gene copies were significantly decreased in STS and ACV treatment groups at 72 h and 96 h (p < 0.05), both in the DNA and in the mRNA level. Furthermore, the expression of gB protein was also inhibited by STS at 24, 72, and 96 h. DISCUSSION AND CONCLUSION: Our study demonstrated that STS could effectively inhibit the MDV replication by suppressing gB gene/protein expression in cell culture.