Host-cell dependent role of phosphorylated keratin 8 during influenza A/NWS/33 virus (H1N1) infection in mammalian cells

ABSTRACTLipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS-containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus-like particles.IMPORTANCEThe lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry.

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Mammalian Diaphanous-related formin-1 restricts early phases of influenza A/NWS/33 virus (H1N1) infection in LLC-MK2 cells by affecting cytoskeleton dynamics

Molecular and Cellular Biochemistry ◽

10.1007/s11010-017-3107-9 ◽

2017 ◽

Vol 437 (1-2) ◽

pp. 185-201 ◽

Cited By ~ 4

Author(s):

Flora De Conto ◽

Alessandra Fazzi ◽

Sergey V. Razin ◽

Maria Cristina Arcangeletti ◽

Maria Cristina Medici ◽

...

Keyword(s):

Influenza A ◽

Virus H1n1 ◽

H1n1 Infection ◽

Cytoskeleton Dynamics ◽

Early Phases

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Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection

Journal of Pharmacy and Pharmacology ◽

10.1111/jphp.12529 ◽

2016 ◽

Vol 68 (3) ◽

pp. 406-420 ◽

Cited By ~ 23

Author(s):

Hyemin Kim ◽

Mirim Jang ◽

Yejin Kim ◽

Jiyea Choi ◽

Jane Jeon ◽

...

Keyword(s):

Vitamin C ◽

Influenza A Virus ◽

Lung Inflammation ◽

Influenza A ◽

Immune Cell ◽

Cell Activity ◽

Virus H1n1 ◽

H1n1 Infection ◽

Red Ginseng

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Dual Role for Transforming Growth Factor β-Dependent Signaling in Trypanosoma cruzi Infection of Mammalian Cells

Infection and Immunity ◽

10.1128/iai.68.4.2077-2081.2000 ◽

2000 ◽

Vol 68 (4) ◽

pp. 2077-2081 ◽

Cited By ~ 37

Author(s):

Belinda S. Hall ◽

Miercio A. Pereira

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Trypanosoma Cruzi ◽

Host Cell ◽

Cell Lines ◽

Mammalian Cells ◽

Transforming Growth Factor ◽

Growth Arrest ◽

Transforming Growth Factor Β

ABSTRACT Expression of functional transforming growth factor β (TGF-β) receptors (TβR) is required for the invasion of mammalian cells by the protozoan parasite Trypanosoma cruzi. However, the precise role of this host cell signaling complex in T. cruzi infection is unknown. To investigate the role of the TGF-β signaling pathway, infection levels were studied in the mink lung epithelial cell lines JD1, JM2, and JM3. These cells express inducible mutant TβR1 proteins that cannot induce growth arrest in response to TGF-β but still transmit the signal for TGF-β-dependent gene expression. In the absence of mutant receptor expression, trypomastigotes invaded the cells at a low level. Induction of the mutant receptors caused an increase in infection in all three cell lines, showing that the requirement for TGF-β signaling at invasion can be divorced from TGF-β-induced growth arrest. TGF-β pretreatment of mink lung cells expressing wild-type TβR1 caused a marked enhancement of infection, but no enhancement was seen in JD1, JM2, and JM3 cells, showing that the ability of TGF-β to stimulate infection is associated with growth arrest. Likewise, expression of SMAD7 or SMAD2SA, inhibitors of TGF-β signaling, did not block infection by T. cruzi but did block the enhancement of infection by TGF-β. Taken together, these results show that there is a dual role for TGF-β signaling in T. cruzi infection. The initial invasion of the host cell is independent of both TGF-β-dependent gene expression and growth arrest, but TGF-β stimulation of infection requires a fully functional TGF-β signaling pathway.

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Severe Influenza A Virus (H1N1) Infection in Pregnancy

Obstetrics and Gynecology ◽

10.1097/aog.0b013e3181cbc7c5 ◽

2010 ◽

Vol 115 (Supplement) ◽

pp. 412-414 ◽

Cited By ~ 13

Author(s):

Cathleen M. Brown

Keyword(s):

Influenza A Virus ◽

Influenza A ◽

Virus H1n1 ◽

H1n1 Infection ◽

Severe Influenza ◽

In Pregnancy

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Polymorphisms in Processing and Antigen Presentation-Related Genes and Their Association with Host Susceptibility to Influenza A/H1N1 2009 Pandemic in a Mexican Mestizo Population

Viruses ◽

10.3390/v12111224 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1224

Author(s):

Marco Antonio Ponce-Gallegos ◽

Aseneth Ruiz-Celis ◽

Enrique Ambrocio-Ortiz ◽

Gloria Pérez-Rubio ◽

Alejandra Ramírez-Venegas ◽

...

Keyword(s):

Influenza A ◽

Host Susceptibility ◽

Nucleotide Polymorphisms ◽

H1n1 Infection ◽

Single Nucleotide ◽

Mexican Mestizo ◽

Influenza A H1n1 ◽

Mexican Mestizo Population ◽

Reduced Risk

(1) Background: The influenza A/H1N1 pdm09 virus rapidly spread throughout the world. Despite the inflammatory and virus-degradation pathways described in the pathogenesis of influenza A virus (IAV) infection, little is known about the role of the single nucleotide polymorphisms (SNPs) in the genes involved in the processing and antigenic presentation-related mechanisms. (2) Methods: In this case-control study, we evaluated 17 SNPs in five genes (TAP1, TAP2, TAPBP, PSMB8, and PSMB9). One hundred and twenty-eight patients with influenza A/H1N1 infection (INF-P) and 111 healthy contacts (HC) were included; all of them are Mexican mestizo. (3) Results: In allele and genotype comparison, the rs241433/C allele (TAP2), as well as AG haplotype (rs3763365 and rs4148882), are associated with reduced risk for influenza A/H1N1 infection (p < 0.05). On the other hand, the rs2071888G allele (TAPBP) and GG haplotype (rs3763365 and rs9276810) are associated with a higher risk for influenza A/H1N1 infection. In addition, after adjustment for covariates, the association to a reduced risk for influenza A/H1N1 infection remains with rs241433/C allele (p < 0.0001, OR = 0.24, 95% CI = 0.13–0.43), and the association with TAPBP is also maintained with the G allele (p = 0.0095, OR = 1.89, 95% CI = 1.17–3.06) and GG genotype models (p < 0.05, OR = 2.18, 95% CI = 1.27–3.74). (4) Conclusion: The rs241433/C allele and AC genotype (TAP2) and the AG haplotype are associated with a reduced risk for influenza A/H1N1 infection. In addition, the rs2071888/G allele and GG genotype (TAPBP) and the GG haplotype are associated with a higher risk for developing influenza A/H1N1 infection in a Mexican mestizo population.

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Alveolar Neutrophilic Recruitment in COVID-19 May Not be Mediated by Th17 Response

10.21203/rs.3.rs-36238/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Marina L V Azevedo ◽

Caroline Busatta Vaz de Paula ◽

Seigo Nagashima ◽

Cleber Machado de Souza ◽

Anna Flavia Miggiolaro Ribeiro ◽

...

Keyword(s):

Influenza A ◽

Group Discussion ◽

Viral Persistence ◽

Tissue Expression ◽

Th2 Cells ◽

Control Group ◽

H1n1 Subtype ◽

Virus H1n1 ◽

Th17 Response

Abstract Introduction: The COVID-19 current pandemic disease differs from the H1N1pdm09 caused by Influenza A virus H1N1 subtype, by how it induces a pro-inflammatory response in infected lungs. Objective: Investigate the role of Th17 response in the pathogenesis of COVID-19 injury by analyzing the tissue expression of interleukins 8 and 17A and the neutrophils in lung samples of patients who die of COVID-19, comparing to H1N1pdm09. Study design and post-mortem results: Six lung samples from patients SARS-CoV-2 infected (COVID-19 group), and ten lung samples from adults who died from H1N1pdm09 (H1N1 group), were tested. A control group was also added to the study. H&E slides were used for neutrophils scoring. The tissue expression of IL-8 and IL-17A was identified by immunohistochemistry. Tissue expression increasing of IL-17A and IL-8 and a higher number of neutrophils were identified in samples from the H1N1 group when compared to the COVID-19 group. Discussion: It is suggested that the SARS-CoV-2 virus evokes an exacerbated response of the host's immune system but differs from that observed in the H1N1pdm09 disease because it may not be trigger by Th17 response. With the low expression of IL-8, IL-17A, neutrophil recruitment to the site of infection becomes impaired, resulting in viral persistence. On the other hand, in the COVID-19 disease, the immune response by Th2 cells seems to be exacerbated, observed by the extent of the lung injury. This uncontrolled response and, mainly, the lack of a therapeutic target, culminates in disease progression and, consequently, in shorter survival time.

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