The effect of avian influenza virus NS1 allele on virus replication and innate gene expression in avian cells

Adams, Sean; Xing, Zheng; Li, Jinling; Mendoza, Kristelle M.; Pérez, Daniel R.; Reed, Kent; Cardona, Carol J.

doi:10.1016/j.molimm.2013.05.236

Cited by 25 publications

(21 citation statements)

References 48 publications

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“…The NS1 protein, one of the two proteins encoded by the NS gene segment, is able to inhibit the host innate immune response by antagonizing interferon. Viruses with allele A of the NS1 protein replicated more than did those with allele B in chicken and turkey cells; in contrast, viruses with allele B of the NS1 protein replicated more and to higher titers than did those with allele A in duck cells (34).…”

Section: Discussionmentioning

confidence: 84%

Long-Term Effect of Serial Infections with H13 and H16 Low-Pathogenic Avian Influenza Viruses in Black-Headed Gulls

Verhagen

Höfle

Amerongen

et al. 2015

J Virol

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Infections of domestic and wild birds with low-pathogenic avian influenza viruses (LPAIVs) have been associated with protective immunity to subsequent infection. However, the degree and duration of immunity in wild birds from previous LPAIV infection, by the same or a different subtype, are poorly understood. Therefore, we inoculated H13N2 (A/black-headed gull/Netherlands/7/ 2009) and H16N3 (A/black-headed gull/Netherlands/26/2009) LPAIVs into black-headed gulls (Chroicocephalus ridibundus), their natural host species, and measured the long-term immune response and protection against one or two reinfections over a period of >1 year. This is the typical interval between LPAIV epizootics in wild birds. Reinfection with the same virus resulted in progressively less virus excretion, with complete abrogation of virus excretion after two infections for H13 but not H16. However, reinfection with the other virus affected neither the level nor duration of virus excretion. Virus excretion by immunologically naive birds did not differ in total levels of excreted H13 or H16 virus between first-and second-year birds, but the duration of H13 excretion was shorter for second-year birds. Furthermore, serum antibody levels did not correlate with protection against LPAIV infection. LPAIV-infected gulls showed no clinical signs of disease. These results imply that the epidemiological cycles of H13 and H16 in black-headed gulls are relatively independent from each other and depend mainly on infection of firstyear birds. IMPORTANCELow-pathogenic avian influenza viruses (LPAIVs) circulate mainly in wild water birds but are occasionally transmitted to other species, including humans, where they cause subclinical to fatal disease. To date, the effect of LPAIV-specific immunity on the epidemiology of LPAIV in wild birds is poorly understood. In this study, we investigated the effect of H13 and H16 LPAIV infection in black-headed gulls on susceptibility and virus excretion of subsequent infection with the same or the other virus within the same breeding season and between breeding seasons. These are the only two LPAIV hemagglutinin subtypes predominating in this species. The findings suggest that H13 and H16 LPAIV cycles in black-headed gull populations are independent of each other, indicate the importance of first-year birds in LPAIV epidemiology, and emphasize the need for alternatives to avian influenza virus (AIV)-specific serum antibodies as evidence of past LPAIV infection and correlates of protection against LPAIV infection in wild birds.

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Section: Discussionmentioning

confidence: 84%

Long-Term Effect of Serial Infections with H13 and H16 Low-Pathogenic Avian Influenza Viruses in Black-Headed Gulls

Verhagen

Höfle

Amerongen

et al. 2015

J Virol

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“…After invasion of host cells, some virus-encoded proteins are used to regulate the host's environment, thus helping to increase virus replication (50)(51)(52)(53).Previous studies have revealed that the nsp1 proteins of coronaviruses can regulate the host protein synthesis and help the virus escape the host's immune interference (25,27,43,45,54). The highly variable sequence homology of the coronavirus nsp1 proteins may lead to the diverse mechanisms for inhibiting the host gene expression.…”

Section: Discussionmentioning

confidence: 99%

Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1

Shen

Deng

et al. 2018

J Virol

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Porcine epidemic diarrhea virus (PEDV), an enteropathogenic , has caused enormous economic losses in the pork industry. Nonstructural protein 1 (nsp1) is a characteristic feature of alpha- and betacoronaviruses, which exhibits both functional conservation and mechanistic diversity in inhibiting host gene expression and antiviral responses. However, the detailed structure and molecular mechanisms underlying the nsp1 inhibition of host gene expression remain unclear. Here, we report the first full-length crystal structure of nsp1 from PEDV. The structure displays a six-stranded β-barrel fold in the middle of two α-helices. The core structure of PEDV nsp1 shows high similarity to those of severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 and transmissible gastroenteritis virus (TGEV) nsp1, despite its low degree of sequence homology. Using ribopuromycylation and luciferase reporter assays, we showed that PEDV nsp1 can dramatically inhibit general host gene expression. Furthermore, three motifs (amino acids [aa] 67 to 71, 78 to 85, and 103 to 110) of PEDV nsp1 create a stable functional region for inhibiting protein synthesis, differing considerably from nsp1. These results elucidate the detailed structural basis through which PEDV nsp1 inhibits host gene expression, providing insight into the development of a new attenuated vaccine with nsp1 modifications. Porcine epidemic diarrhea virus (PEDV) has led to tremendous economic losses in the global swine industry. PEDV nsp1 plays a crucial role in inhibiting host gene expression, but its functional mechanism remains unclear. Here, we report the full-length structure of PEDV nsp1, the first among coronaviruses to be reported. The 1.25-Å resolution crystal structure of PEDV nsp1 shows high similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 and transmissible gastroenteritis virus (TGEV) nsp1, despite a lack of sequence homology. Structural and biochemical characterization demonstrated that PEDV nsp1 possesses a stable functional region for inhibition of host protein synthesis, which is formed by loops at residues 67 to 71, 78 to 85, and 103 to 110. The different functional regions in PEDV nsp1 and SARS-CoV nsp1 may explain their distinct mechanisms. Importantly, our structural data are conducive to understanding the mechanism of PEDV nsp1 inhibition of the expression of host genes and may aid in the development of a new attenuated vaccine.

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“…Duck embryo fibroblasts (DEFs) were obtained from 9-day-old specific pathogen free (SPF) duck embryos (purchased from Harbin Veterinary Research Institute, Harbin, China) according to the manufacturer’s instructions [46], cultured in Dulbecco’s modified Eagle’s medium (DMEM/F-12 1:1) (01-172-1ACS, BI, Kibbutz, Beit Haemek, Israel) at pH 7.2, supplemented with 10% fetal bovine serum (FBS) (04-001-1ACS, BI, Kibbutz, Beit Haemek, Israel), 100 U/mL penicillin and 100 mg/mL streptomycin (P1400, Solarbio Science & Technology Co., Ltd., Beijing, China), and grown in 25 cm 2 flask (07-8025, BIOLOGIX, Kennebunk, ME, USA) at 37 °C in a 5% CO 2 cell incubator.…”

Section: Methodsmentioning

confidence: 99%

Comparative Transcriptomic Analysis of Immune-Related Gene Expression in Duck Embryo Fibroblasts Following Duck Tembusu Virus Infection

Lin

Tang

et al. 2018

IJMS

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Duck is a major waterfowl species in China, providing high-economic benefit with a population of up to 20–30 billion per year. Ducks are commonly affected by severe diseases, including egg-drop syndrome caused by duck Tembusu virus (DTMUV). The immune mechanisms against DTMUV invasion and infection remain poorly understood. In this study, duck embryo fibroblasts (DEFs) were infected with DTMUV and harvested at 12 and 24 h post-infection (hpi), and their genomes were sequenced. In total, 911 (764 upregulated and 147 downregulated genes) and 3008 (1791 upregulated and 1217 downregulated) differentially expressed genes (DEGs) were identified at 12 and 24 hpi, respectively. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that DEGs were considerably enriched in immune-relevant pathways, including Toll-like receptor signaling pathway, Cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway, Chemokine signaling pathway, NOD-like receptor signaling pathway, and Hematopoietic cell lineage at both time points. The key DEGs in immune system included those of the cytokines (IFN α2, IL-6, IL-8L, IL-12B, CCR7, CCL19, and CCL20), transcription factors or signaling molecules (IRF7, NF-κB, STAT1, TMEM173, and TNFAIP3), pattern recognition receptors (RIG-I and MDA5), and antigen-presenting proteins (CD44 and CD70). This suggests DTMUV infection induces strong proinflammatory/antiviral effects with enormous production of cytokines. However, these cytokines could not protect DEFs against viral attack. Our data revealed valuable transcriptional information regarding DTMUV-infected DEFs, thereby broadening our understanding of the immune response against DTMUV infection; this information might contribute in developing strategies for controlling the prevalence of DTMUV infection.

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The effect of avian influenza virus NS1 allele on virus replication and innate gene expression in avian cells

Cited by 25 publications

References 48 publications

Long-Term Effect of Serial Infections with H13 and H16 Low-Pathogenic Avian Influenza Viruses in Black-Headed Gulls

Long-Term Effect of Serial Infections with H13 and H16 Low-Pathogenic Avian Influenza Viruses in Black-Headed Gulls

Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1

Comparative Transcriptomic Analysis of Immune-Related Gene Expression in Duck Embryo Fibroblasts Following Duck Tembusu Virus Infection

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