Systems biology of virus-host signaling network interactions

Xue, Qinghong; Miller‐Jensen, Kathryn

doi:10.5483/bmbrep.2012.45.4.213

Cited by 12 publications

(11 citation statements)

References 59 publications

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“…The response of cells to the surrounding alterations is through translating the complicated network of various protein interactions into functional response . The different response of cells in confronting with viral pathogenesis agents can change the signaling pathways via emulation of the proteins interactions . Hence, analysis of these extensive data is an effective way to propose pathogenesis mechanism of a virus …”

Section: Introductionmentioning

confidence: 99%

Human T‐lymphotropic virus 1 (HTLV‐1) pathogenesis: A systems virology study

Mozhgani¹,

Zarei-Ghobadi²,

Teymoori‐Rad³

et al. 2018

J of Cellular Biochemistry

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The main mechanisms of interaction between Human T-lymphotropic virus type 1 (HTLV-1) and its hosts in the manifestation of the related disease including HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T-cell leukemia/lymphoma (ATLL) are yet to be determined. It is pivotal to find out the changes in the genes expression toward an asymptomatic or symptomatic states. To this end, the systems virology analysis was performed. Firstly, the differentially expressed genes (DEGs) were taken pairwise among the four sample sets of Normal, Asymptomatic Carriers (ACs), ATLL, and HAM/TSP. Afterwards, the protein-protein interaction networks were reconstructed utilizing the hub genes. In conclusion, the pathways of cells proliferation and transformation were identified in the ACs state. In addition to immune pathways in ATLL, the inflammation and cancer pathways were discened in both diseases of ATLL and HAM/TSP. The outcomes can specify the genes involved in the pathogenesis and help to design the drugs in the future.

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Section: Introductionmentioning

confidence: 99%

Human T‐lymphotropic virus 1 (HTLV‐1) pathogenesis: A systems virology study

Mozhgani¹,

Zarei-Ghobadi²,

Teymoori‐Rad³

et al. 2018

J of Cellular Biochemistry

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“…While the inherent redundancy of cellular networks prevents critical network failure upon disruption of a single node by random events (e.g., mutations), cellular networks are susceptible to targeted attacks (e.g., by pathogens) which disrupt key controllers of the network (10), namely, the "hub proteins" to which many of the subsidiary nodes connect. Where a targeted approach by a pathogen disrupts the function of the hub protein, the result is the disruption of key functions of the cellular network to which the hub protein is connected.…”

mentioning

confidence: 99%

Adenovirus E1A Targets the DREF Nuclear Factor To Regulate Virus Gene Expression, DNA Replication, and Growth

Radko

Koleva

James

et al. 2014

J Virol

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The adenovirus E1A gene is the first gene expressed upon viral infection. E1A remodels the cellular environment to maximize permissivity for viral replication. E1A is also the major transactivator of viral early gene expression and a coregulator of a large number of cellular genes. E1A carries out its functions predominantly by binding to cellular regulatory proteins and altering their activities. The unstructured nature of E1A enables it to bind to a large variety of cellular proteins and form new molecular complexes with novel functions. The C terminus of E1A is the least-characterized region of the protein, with few known binding partners. Here we report the identification of cellular factor DREF (ZBED1) as a novel and direct binding partner of E1A. Our studies identify a dual role for DREF in the viral life cycle. DREF contributes to activation of gene expression from all viral promoters early in infection. Unexpectedly, it also functions as a growth restriction factor for adenovirus as knockdown of DREF enhances virus growth and increases viral genome copy number late in the infection. We also identify DREF as a component of viral replication centers. E1A affects the subcellular distribution of DREF within PML bodies and enhances DREF SUMOylation. Our findings identify DREF as a novel E1A C terminus binding partner and provide evidence supporting a role for DREF in viral replication. IMPORTANCEThis work identifies the putative transcription factor DREF as a new target of the E1A oncoproteins of human adenovirus. DREF was found to primarily localize with PML nuclear bodies in uninfected cells and to relocalize into virus replication centers during infection. DREF was also found to be SUMOylated, and this was enhanced in the presence of E1A. Knockdown of DREF reduced the levels of viral transcripts detected at 20 h, but not at 40 h, postinfection, increased overall virus yield, and enhanced viral DNA replication. DREF was also found to localize to viral promoters during infection together with E1A. These results suggest that DREF contributes to activation of viral gene expression. However, like several other PML-associated proteins, DREF also appears to function as a growth restriction factor for adenovirus infection.T he interaction of the adenovirus early 1A (E1A) proteins with mammalian regulatory factors has been heavily exploited to elucidate the molecular basis by which they control cellular processes (1-5). Studying the interactions of E1A with new cellular targets provides an exciting opportunity to identify and dissect critical mechanisms controlling mammalian transcription, growth, and differentiation, as well as to identify novel viral regulatory mechanisms. The organization of E1A into short peptide motifs (MoRFs) (6) involved in protein interactions has significantly enriched our understanding of eukaryotic protein function. Identification and characterization of novel MoRFs within E1A allow their subsequent detection in other proteins, which suggests novel interactions leading to signifi...

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“…It is possible to divide systems biology studies into two categories: static studies, which take a "snapshot" of a biological network under a single condition, or limited set of conditions; and dynamic studies, which measure time-dependent changes in the network following treatment with environmental stimuli or other biological cues. Both approaches have the potential to significantly increase our understanding of the complex mechanisms involved in viral infection (Xue and Miller-Jensen, 2012). However application of dynamic systems biology approaches to virus-host signaling interactions, in which multiple signals in the network are measured simultaneously over time, may provide a better understanding of how a virus hijacks the host protein signaling network and wires signaling in favor of virus survival and replication.…”

Section: Static Studies and Dynamic Studiesmentioning

confidence: 99%

“…Regrettably, 'systems biology' is often used as a blanket term, mistakenly referenced in studies utilizing only high-throughput technologies or incorporated into titles to give extra weight or novelty. Integration of multiple high-throughput data types represents just a single dimension of the field necessary to elucidate host responses to infection (Xue and Miller-Jensen, 2012). In the case of systems virology, biological systems may range from virus-infected cells to tissues to whole organisms.…”

Section: Introductionmentioning

confidence: 99%

“…Besides, mathematical modelling of interaction networks is essential for researchers to better relate changes at the molecular level to the global properties observed within a biological system during infection. Molecular studies of individual pathways have uncovered many viral host-protein targets; however, it is difficult to predict how viral perturbations will affect the signalling network as a whole (Xue and Miller-Jensen, 2012). Systems biology has the potential to discover novel prohost therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

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Systems biology approach: Panacea for unravelling host-virus interactions and dynamics of vaccine induced immune response

et al. 2016

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Systems biology is an interdisciplinary research field in life sciences, which involves a comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. For the past 50 years the discipline of virology has overly focused on the pathogen itself. However, we now know that the host response is equally or more important in defining the eventual pathological outcome of infection. Systems biology has in recent years been increasingly recognised for its importance to infectious disease research. Hostvirus interactions can be better understood by taking into account the dynamical molecular networks that constitute a biological system. To decipher the pathobiological mechanisms of any disease requires a deep knowledge of how multiple and concurrent signal-transduction pathways operate and are deregulated. Hence the intricacies of signalling pathways can be dissected only by system level approaches.

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Systems biology of virus-host signaling network interactions

Cited by 12 publications

References 59 publications

Human T‐lymphotropic virus 1 (HTLV‐1) pathogenesis: A systems virology study

Human T‐lymphotropic virus 1 (HTLV‐1) pathogenesis: A systems virology study

Adenovirus E1A Targets the DREF Nuclear Factor To Regulate Virus Gene Expression, DNA Replication, and Growth

Systems biology approach: Panacea for unravelling host-virus interactions and dynamics of vaccine induced immune response

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