scholarly journals Comparing host module activation patterns and temporal dynamics in infection by influenza H1N1 viruses

2021 ◽  
Author(s):  
Irina Nudelman ◽  
Daniil Kudrin ◽  
German Nudelman ◽  
Raamesh Deshpande ◽  
Boris M. Hartmann ◽  
...  
Keyword(s):  
Time Series ◽  
Temporal Dynamics ◽  
Functional Module ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Host Cells ◽  
Integrative Approach ◽  
Functional Modules ◽  
Expression Data ◽  
Virus Strains

Influenza is a serious global health threat that shows varying pathogenicity among different virus strains. Understanding similarities and differences among activated functional pathways in the host responses can help elucidate therapeutic targets responsible for pathogenesis. To compare the types and timing of functional modules activated in host cells by four influenza viruses of varying pathogenicity, we developed a new DYNAmic MOdule (DYNAMO) method that addresses the need to compare functional module utilization over time. This integrative approach overlays whole genome time series expression data onto an immune-specific functional network, and extracts conserved modules exhibiting either different temporal patterns or overall transcriptional activity. We identified a common core response to influenza virus infection that is temporally shifted for different viruses. We also identified differentially regulated functional modules that reveal unique elements of responses to different virus strains. Our work highlights the usefulness of combining time series gene expression data with a functional interaction map to capture temporal dynamics of the same cellular pathways under different conditions. Our results help elucidate conservation of the immune response both globally and at a granular level, and provide mechanistic insight into the differences in the host response to infection by influenza strains of varying pathogenicity

scholarly journals Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses

2021 ◽  
Vol 12 ◽  
Author(s):  
Irina Nudelman ◽  
Daniil Kudrin ◽  
German Nudelman ◽  
Raamesh Deshpande ◽  
Boris M. Hartmann ◽  
...  
Keyword(s):  
Time Series ◽  
Temporal Dynamics ◽  
Functional Module ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Host Cells ◽  
Integrative Approach ◽  
Functional Modules ◽  
Expression Data ◽  
Virus Strains

Influenza is a serious global health threat that shows varying pathogenicity among different virus strains. Understanding similarities and differences among activated functional pathways in the host responses can help elucidate therapeutic targets responsible for pathogenesis. To compare the types and timing of functional modules activated in host cells by four influenza viruses of varying pathogenicity, we developed a new DYNAmic MOdule (DYNAMO) method that addresses the need to compare functional module utilization over time. This integrative approach overlays whole genome time series expression data onto an immune-specific functional network, and extracts conserved modules exhibiting either different temporal patterns or overall transcriptional activity. We identified a common core response to influenza virus infection that is temporally shifted for different viruses. We also identified differentially regulated functional modules that reveal unique elements of responses to different virus strains. Our work highlights the usefulness of combining time series gene expression data with a functional interaction map to capture temporal dynamics of the same cellular pathways under different conditions. Our results help elucidate conservation of the immune response both globally and at a granular level, and provide mechanistic insight into the differences in the host response to infection by influenza strains of varying pathogenicity.

scholarly journals Polymorphisms in the haemagglutinin gene influenced the viral shedding of pandemic 2009 influenza virus in swine

2014 ◽  
Vol 95 (12) ◽  
pp. 2618-2626 ◽  
Author(s):  
Alessio Lorusso ◽  
Janice R. Ciacci-Zanella ◽  
Eraldo L. Zanella ◽  
Lindomar Pena ◽  
Daniel R. Perez ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Consensus Sequence ◽  
Influenza Virus Infection ◽  
Antigenic Site ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Viral Shedding

Interactions between the viral surface glycoprotein haemagglutinin (HA) and the corresponding receptors on host cells is one important aspect of influenza virus infection. Mutations in HA have been described to affect pathogenicity, antigenicity and the transmission of influenza viruses. Here, we detected polymorphisms present in HA genes of two pandemic 2009 H1N1 (H1N1pdm09) isolates, A/California/04/2009 (Ca/09) and A/Mexico/4108/2009 (Mx/09), that resulted in amino acid changes at positions 186 (S to P) and 194 (L to I) of the mature HA1 protein. Although not reported in the published H1N1pdm09 consensus sequence, the P186 genotype was more readily detected in primary infected and contact-naïve pigs when inoculated with a heterogeneous mixed stock of Ca/09. Using reverse genetics, we engineered Ca/09 and Mx/09 genomes by introducing Ca/09 HA with two naturally occurring variants expressing S186/I194 (HA-S/I) and P186/L194 (HA-P/L), respectively. The Ca/09 HA with the combination of P186/L194 with either the Ca/09 or Mx/09 backbone resulted in higher and prolonged viral shedding in naïve pigs. This efficiency appeared to be more likely through an advantage in cell surface attachment rather than replication efficiency. Although these mutations occurred within the receptor-binding pocket and the Sb antigenic site, they did not affect serological cross-reactivity. Relative increases of P186 in publicly available sequences from swine H1N1pdm09 viruses supported the experimental data, indicating this amino acid substitution conferred an advantage in swine.

Tissue distribution of human and avian type sialic acid influenza virus receptors in domestic cat

2013 ◽  
Vol 61 (4) ◽  
pp. 537-546 ◽  
Author(s):  
Heng Wang ◽  
Xintao Wu ◽  
Yanfen Cheng ◽  
Yufu An ◽  
Zhangyong Ning
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Gastrointestinal Tract ◽  
Virus Infection ◽  
Tissue Distribution ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Domestic Cat ◽  
Host Cells ◽  
Human Influenza

Infection of host cells with the influenza virus is mediated by specific interactions between the viral haemagglutinin (HA) and cell oligosaccharides containing sialic acid (SA) residues. Avian and human influenza viruses bind to alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors, respectively. To date, there have been no detailed tissue distribution data on alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors in the domestic cat, a relatively new mammalian host for influenza virus infections. In this study, the tissue distribution of human and avian type sialic acid influenza receptors was determined in various organs (respiratory tract, gastrointestinal tract, brain, cerebellum, spleen, kidney, heart and pancreas) of domestic cat by binding with the lectinsMaackia amurensisagglutinin II (MAA II) andSambucus nigraagglutinin (SNA), respectively. The results revealed that both alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors were extensively detected in the trachea, bronchus, lung, kidney, spleen, pancreas and gastrointestinal tract. Endothelial cells of gastrointestinal tract organs were negative for alpha-2, 3 sialic acid-linked receptors in cats. The presence of alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors in the major organs examined in the present study suggests that each major organ may be affected by influenza virus infection. Because of receptor distribution in the gastrointestinal tract, the experimental infection of cats with human influenza virus may be relatively easy while their infection with avian influenza virus may be difficult. These data can explain the involvement of multiple organs in influenza virus infection and should help investigators interpret the results obtained when cats are infected with influenza virus and estimate the risk of infection between cats and humans.

scholarly journals Distinct miRNA Profile of Cellular and Extracellular Vesicles Released from Chicken Tracheal Cells Following Avian Influenza Virus Infection

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 438
Author(s):  
Kelsey O’Dowd ◽  
Mehdi Emam ◽  
Mohamed Reda El Khili ◽  
Amin Emad ◽  
Eveline M. Ibeagha-Awemu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Extracellular Vesicles ◽  
Viral Infections ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Host Cells ◽  
Control Group ◽  
Antiviral Responses

Innate responses provide the first line of defense against viral infections, including the influenza virus at mucosal surfaces. Communication and interaction between different host cells at the early stage of viral infections determine the quality and magnitude of immune responses against the invading virus. The release of membrane-encapsulated extracellular vesicles (EVs), from host cells, is defined as a refined system of cell-to-cell communication. EVs contain a diverse array of biomolecules, including microRNAs (miRNAs). We hypothesized that the activation of the tracheal cells with different stimuli impacts the cellular and EV miRNA profiles. Chicken tracheal rings were stimulated with polyI:C and LPS from Escherichia coli 026:B6 or infected with low pathogenic avian influenza virus H4N6. Subsequently, miRNAs were isolated from chicken tracheal cells or from EVs released from chicken tracheal cells. Differentially expressed (DE) miRNAs were identified in treated groups when compared to the control group. Our results demonstrated that there were 67 up-regulated miRNAs, 157 down-regulated miRNAs across all cellular and EV samples. In the next step, several genes or pathways targeted by DE miRNAs were predicted. Overall, this study presented a global miRNA expression profile in chicken tracheas in response to avian influenza viruses (AIV) and toll-like receptor (TLR) ligands. The results presented predicted the possible roles of some DE miRNAs in the induction of antiviral responses. The DE candidate miRNAs, including miR-146a, miR-146b, miR-205a, miR-205b and miR-449, can be investigated further for functional validation studies and to be used as novel prophylactic and therapeutic targets in tailoring or enhancing antiviral responses against AIV.

scholarly journals Divergent Requirement of Fc-Fcγ Receptor Interactions for In Vivo Protection against Influenza Viruses by Two Pan-H5 Hemagglutinin Antibodies

2017 ◽  
Vol 91 (11) ◽  
Author(s):  
Shuangshuang Wang ◽  
Huanhuan Ren ◽  
Wenbo Jiang ◽  
Honglin Chen ◽  
Hongxing Hu ◽  
...  
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
Virus Strain ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Target Cells ◽  
Fcγ Receptor ◽  
Receptor Binding Site ◽  
Virus Strains

ABSTRACT Recent studies have shown that Fc-Fcγ receptor (FcγR) interactions are required for in vivo protection against influenza viruses by broadly reactive anti-hemagglutinin (HA) stem, but not virus strain-specific, anti-receptor binding site (RBS), antibodies (Abs). Since only a few Abs recognizing epitopes in the head region but outside the RBS have been tested against single-challenge virus strains, it remains unknown whether Fc-FcγR interactions are required for in vivo protection by Abs recognizing epitopes outside the RBS and whether the requirement is virus strain specific or epitope specific. In the present study, we therefore investigated the requirements for in vivo protection using two pan-H5 Abs, 65C6 and 100F4. We generated chimeric Abs, 65C6/IgG2a and 100F4/IgG2a, which preferentially engage activating FcγRs, and isogenic forms, 65C6/D265A and 100F4/D265A, which do not bind FcγR. Virus neutralizing activity, binding, antibody-dependent cellular cytotoxicity (ADCC), and in vivo protection of these Abs were compared using three H5 strains, A/Shenzhen/406H/2006 (SZ06), A/chicken/Shanxi/2/2006 (SX06), and A/chicken/Netherlands/14015526/2014 (NE14). We found that all four chimeric Abs bound and neutralized the SZ06 and NE14 strains but poorly inhibited the SX06 strain. 65C6/IgG2a and 100F4/IgG2a, but not 65C6/D265A and 100F4/D265A, mediated ADCC against target cells expressing HA derived from all three virus strains. Interestingly, both 65C6/IgG2a and 65C6/D265A demonstrated comparable protection against all three virus strains in vivo; however, 100F4/IgG2a, but not 100F4/D265A, showed in vivo protection. Thus, we conclude that Fc-FcγR interactions are required for in vivo protection by 100F4, but not by 65C6, and therefore, protection is not virus strain specific but epitope specific. IMPORTANCE Abs play an important role in immune protection against influenza virus infection. Fc-FcγR interactions are required for in vivo protection by broadly neutralizing antistem, but not by virus strain-specific, anti-receptor binding site (RBS), Abs. Whether such interactions are necessary for protection by Abs that recognize epitopes outside RBS is not fully understood. In the present study, we investigated in vivo protection mechanisms against three H5 strains by two pan-H5 Abs, 65C6 and 100F4. We show that although these two Abs have similar neutralizing, binding, and ADCC activities against all three H5 strains in vitro, they have divergent requirements for Fc-FcγR interactions to protect against the three H5 strains in vivo. The Fc-FcγR interactions are required for in vivo protection by 100F4, but not by 65C6. Thus, we conclude that Fc-FcγR interactions for in vivo protection by pan-H5 Abs is not strain specific, but epitope specific.

scholarly journals Microtubules in Influenza Virus Entry and Egress

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 117 ◽  
Author(s):  
Caitlin Simpson ◽  
Yohei Yamauchi
Keyword(s):  
Influenza Virus ◽  
Cell Biology ◽  
Large Scale ◽  
Structural Changes ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Host Cells ◽  
Respiratory Pathogens ◽  
Microtubule Network ◽  
Vaccination Programs

Influenza viruses are respiratory pathogens that represent a significant threat to public health, despite the large-scale implementation of vaccination programs. It is necessary to understand the detailed and complex interactions between influenza virus and its host cells in order to identify successful strategies for therapeutic intervention. During viral entry, the cellular microenvironment presents invading pathogens with a series of obstacles that must be overcome to infect permissive cells. Influenza hijacks numerous host cell proteins and associated biological pathways during its journey into the cell, responding to environmental cues in order to successfully replicate. The cellular cytoskeleton and its constituent microtubules represent a heavily exploited network during viral infection. Cytoskeletal filaments provide a dynamic scaffold for subcellular viral trafficking, as well as virus-host interactions with cellular machineries that are essential for efficient uncoating, replication, and egress. In addition, influenza virus infection results in structural changes in the microtubule network, which itself has consequences for viral replication. Microtubules, their functional roles in normal cell biology, and their exploitation by influenza viruses will be the focus of this review.

Lipid-mediated biosynthetic labeling strategy for in vivo dynamic tracing of avian influenza virus infection

2022 ◽  
pp. 088532822110632
Author(s):  
Junfang Liu ◽  
Minhong Su ◽  
Xin Chen ◽  
Zhongli Li ◽  
Zekui Fang ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Viral Infection ◽  
Near Infrared ◽  
Influenza Virus Infection ◽  
Infection Process ◽  
Influenza Viruses ◽  
Viral Envelope ◽  
Host Cells

Monitoring the infection behavior of avian influenza viruses is crucial for understanding viral pathogenesis and preventing its epidemics among people. A number of viral labeling methods have been utilized for tracking viral infection process, but most of them are laborious or decreasing viral activity. Herein we explored a lipid biosynthetic labeling strategy for dynamical tracking the infection of H5N1 pseudotype virus (H5N1p) in host. Biotinylated lipids (biotinyl Cap-PE) were successfully incorporated into viral envelope when it underwent budding process by taking advantage of host cell-derived lipid metabolism. Biotin-H5N1p virus was effectively in situ–labeled with streptavidin-modified near-infrared quantum dots (NIR SA-QDs) using streptavidin-biotin conjugation with well-preserved virus activities. Dual-labeled imaging obviously shows that H5N1p viruses are primarily taken up in host cells via clathrin-mediated endocytosis. In animal models, Virus-conjugated NIR QDs displayed extraordinary photoluminescence, superior stability, and tissue penetration in lung, allowing us to long-term monitor respiratory viral infection in a noninvasive manner. Importantly, the co-localization of viral hemagglutinin protein and QDs in infected lung further conformed the dynamic infection process of virus in vivo. Hence, this in situ QD-labeling strategy based on cell natural biosynthesis provides a brand-new and reliable tool for noninvasion visualizing viral infection in body in a real-time manner.

scholarly journals Protein functional module identification method combining topological features and gene expression data

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zihao Zhao ◽  
Wenjun Xu ◽  
Aiwen Chen ◽  
Yueyue Han ◽  
Shengrong Xia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Functional Module ◽  
Clustering Algorithms ◽  
Expression Patterns ◽  
Structure Characteristic ◽  
Functional Modules ◽  
Expression Data ◽  
Ppi Network ◽  
Topological Features

Abstract Background The study of protein complexes and protein functional modules has become an important method to further understand the mechanism and organization of life activities. The clustering algorithms used to analyze the information contained in protein-protein interaction network are effective ways to explore the characteristics of protein functional modules. Results This paper conducts an intensive study on the problems of low recognition efficiency and noise in the overlapping structure of protein functional modules, based on topological characteristics of PPI network. Developing a protein function module recognition method ECTG based on Topological Features and Gene expression data for Protein Complex Identification. Conclusions The algorithm can effectively remove the noise data reflected by calculating the topological structure characteristic values in the PPI network through the similarity of gene expression patterns, and also properly use the information hidden in the gene expression data. The experimental results show that the ECTG algorithm can detect protein functional modules better.

Sign in / Sign up

Export Citation Format

Share Document