scholarly journals Comprehensive profiling of translation initiation in influenza virus infected cells

2018 ◽  
Author(s):  
Heather M. Machkovech ◽  
Jesse D. Bloom ◽  
Arvind R. Subramaniam
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Translation Initiation ◽  
Mammalian Cells ◽  
Transmembrane Domain ◽  
Influenza Virus Infection ◽  
Ribosome Profiling ◽  
Epithelial Cell Line ◽  
Human Lung Epithelial Cell ◽  
Evolutionary Forces

AbstractTranslation can initiate at alternate, non-canonical start codons in response to stressful stimuli in mammalian cells. Recent studies suggest that viral infection and anti-viral responses alter sites of translation initiation, and in some cases, lead to production of novel immune epitopes. Here we systematically investigate the extent and impact of alternate translation initiation in cells infected with influenza virus. We perform evolutionary analyses that suggest selection against non-canonical initiation at CUG codons in influenza virus lineages that have adapted to mammalian hosts. We then use ribosome profiling with the initiation inhibitor lactidomycin to experimentally delineate translation initiation sites in a human lung epithelial cell line infected with influenza virus. We identify several candidate sites of alternate initiation in influenza mRNAs, all of which occur at AUG codons that are downstream of canonical initiation codons. One of these candidate downstream start sites truncates 14 amino acids from the N-terminus of the N1 neuraminidase protein, resulting in loss of its cytoplasmic tail and a portion of the transmembrane domain. This truncated neuraminidase protein is expressed on the cell surface during influenza virus infection, is enzymatically active, and is conserved in most N1 viral lineages. Host transcripts induced by the anti-viral response are enriched for translation initiation at non-canonical start sites and non-AUG start codons. Together, our results systematically map the landscape of translation initiation during influenza virus infection, and shed light on the evolutionary forces shaping this landscape.

Host factors involved in influenza virus infection

2020 ◽  
Vol 4 (4) ◽  
pp. 401-410
Author(s):  
Matloob Husain
Keyword(s):  
Influenza Virus ◽  
Plasma Membrane ◽  
Life Cycle ◽  
Virus Infection ◽  
Mammalian Cells ◽  
Influenza Virus Infection ◽  
Host Factors ◽  
Tremendous Amount ◽  
Human Viruses ◽  
Insight Into

Influenza virus causes an acute febrile respiratory disease in humans that is commonly known as ‘flu’. Influenza virus has been around for centuries and is one of the most successful, and consequently most studied human viruses. This has generated tremendous amount of data and information, thus it is pertinent to summarise these for, particularly interdisciplinary readers. Viruses are acellular organisms and exist at the interface of living and non-living. Due to this unique characteristic, viruses require another organism, i.e. host to survive. Viruses multiply inside the host cell and are obligate intracellular pathogens, because their relationship with the host is almost always harmful to host. In mammalian cells, the life cycle of a virus, including influenza is divided into five main steps: attachment, entry, synthesis, assembly and release. To complete these steps, some viruses, e.g. influenza utilise all three parts — plasma membrane, cytoplasm and nucleus, of the cell; whereas others, e.g. SARS-CoV-2 utilise only plasma membrane and cytoplasm. Hence, viruses interact with numerous host factors to complete their life cycle, and these interactions are either exploitative or antagonistic in nature. The host factors involved in the life cycle of a virus could be divided in two broad categories — proviral and antiviral. This perspective has endeavoured to assimilate the information about the host factors which promote and suppress influenza virus infection. Furthermore, an insight into host factors that play a dual role during infection or contribute to influenza virus-host adaptation and disease severity has also been provided.

scholarly journals IRF7 Is Required for the Second Phase Interferon Induction during Influenza Virus Infection in Human Lung Epithelia

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 377 ◽  
Author(s):  
Wenxin Wu ◽  
Wei Zhang ◽  
Lili Tian ◽  
Brent R. Brown ◽  
Matthew S. Walters ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Cell Line ◽  
Human Lung ◽  
De Novo ◽  
Influenza Virus Infection ◽  
Alveolar Epithelial Cells ◽  
Epithelial Cell Line ◽  
Second Phase ◽  
Alveolar Epithelial

Influenza A virus (IAV) infection is a major cause of morbidity and mortality. Retinoic acid-inducible protein I (RIG-I) plays an important role in the recognition of IAV in most cell types, and leads to the activation of interferon (IFN). We investigated mechanisms of RIG-I and IFN induction by IAV in the BCi-NS1.1 immortalized human airway basal cell line and in the A549 human alveolar epithelial cell line. We found that the basal expression levels of RIG-I and regulatory transcription factor (IRF) 7 were very low in BCi-NS1.1 cells. IAV infection induced robust RIG-I and IRF7, not IRF3, expression. siRNA against IRF7 and mitochondrial antiviral-signaling protein (MAVS), but not IRF3, significantly inhibited RIG-I mRNA expression and IFN induction by IAV infection. Most importantly, even without virus infection, IFN-β alone induced RIG-I, and siRNA against IRF7 did not inhibit RIG-I induction by IFN-β. Similar results were found in the alveolar basal epithelial A549 cell line. RIG-I and IRF7 expression in humans is highly inducible and greatly amplified by IFN produced from virus infected cells. IFN induction can be separated into two phases, that initially induced by the virus with basal RIG-I (the first phase), and that induced by the subsequent virus with amplified RIG-I from the first phase IFN (the second phase). The de novo synthesis of IRF7 is required for the second phase IFN induction during influenza virus infection in human lung bronchial and alveolar epithelial cells.

scholarly journals Mini viral RNAs act as innate immune agonists during influenza virus infection

2018 ◽  
Author(s):  
Aartjan J.W. te Velthuis ◽  
Joshua C. Long ◽  
David L.V. Bauer ◽  
Rebecca L.Y. Fan ◽  
Hui-Ling Yen ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Avian Influenza ◽  
Mammalian Cells ◽  
Systemic Disease ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Innate Immune ◽  
Viral Rna ◽  
Viral Rnas

Influenza A virus infection usually causes a mild to moderately severe respiratory disease in humans. However, infection with the 1918 H1N1 pandemic or highly pathogenic avian influenza viruses (HPAIV) of the H5N1 subtype, can lead to viral pneumonia, systemic disease and death. The molecular processes that determine the outcome of influenza virus infection are multifactorial and involve a complex interplay between host, viral, and bacterial factors1. However, it is generally accepted that a strong innate immune dysregulation known as ‘cytokine storm’ contributes to the pathology of pandemic and avian influenza virus infections2–4. The RNA sensor Retinoic acid-inducible gene I (RIG-I) plays an important role in sensing viral infection and initiating a signalling cascade that leads to interferon (IFN) expression5. Here we show that short aberrant RNAs (mini viral RNAs; mvRNAs), produced by the viral RNA polymerase during the replication of the viral RNA genome, bind and activate the intracellular pathogen sensor RIG-I, and lead to the expression of interferon-β. We find that erroneous polymerase activity, dysregulation of viral RNA replication, or the presence of avian-specific amino acids underlie mvRNA generation and cytokine expression in mammalian cells and propose an intramolecular copy-choice mechanism for mvRNA generation. By deep-sequencing RNA samples from lungs of ferrets infected with influenza viruses we show that mvRNAs are generated during infection of animal models. We propose that mvRNAs act as main agonists of RIG-I during influenza virus infection and the ability of influenza virus strains to generate mvRNAs should be considered when assessing their virulence potential.

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