High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells

Chiu, Han-Chen; Hannemann, Holger; Heesom, Kate J; Matthews, David A.; Davidson, Andrew D.

doi:10.1371/journal.pone.0093305

Cited by 58 publications

(49 citation statements)

References 94 publications

(98 reference statements)

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“…It is well recognized that viral infections can induce significant changes in cellular proteomes [30][31][32] and an increase in protein levels during DENV infection may contribute to the increased protein capture measured by qTUX-MS. To address this, we used SILAC-MS to quantify proteome (i.e., total protein abundance) changes following DENV infection. Comparison of qTUX-MS and proteome SILAC ratios showed that the protein abundances for the 93 qTUX-MS-identified vRNA-binding factors remained largely unchanged (Fig 2A, S1 Fig and S1 Dataset).…”

Section: The Majority Of Candidate Host Factors Are Not Altered At Thmentioning

confidence: 99%

Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements

et al. 2016

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BackgroundThere are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses) replication.Methodology/Principal FindingsSeventy-nine novel RNA binding proteins for dengue virus (DENV) were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated.Conclusions/SignificanceThe method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps cellular proteins for efficient amplification.

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Section: The Majority Of Candidate Host Factors Are Not Altered At Thmentioning

confidence: 99%

Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements

et al. 2016

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“…These evidences show that GANAB and P4HB are relevant proteins not only in our 12 interactomes, but also in other host-pathogen systems, which confirm these proteins as possible hallmarks of the host-parasite interaction. Other host proteins common in several parasite interactomes ( Fig 7) such as HYOU1, PDIA3, HSPA9, CTSS, etc., have been already found deregulated upon pathogenic infection [78][79][80][81][82][83].…”

Section: Common Targeted Host Proteins Across Interactomesmentioning

confidence: 99%

An integrative method to unravel the host-parasite interactome: an orthology-based approach

Cuesta-Astroz

Santos

Oliveira

et al. 2017

Preprint

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The study of molecular host-parasite interactions is essential to understand parasitic infection and adaptation within the host system. As well, prevention and treatment of infectious diseases require clear understanding of the molecular crosstalk between parasites and their hosts. As yet, experimental large-scale identification of host-parasite molecular interactions remains challenging and the use of in silico predictions becomes then necessary. Here, we propose a computational integrative approach to predict host-parasite protein-protein interaction (PPI) networks resulting from the infection of human by 12 different parasites. We used an orthology-based method to transfer high-confidence intraspecies interactions obtained from the STRING database to the corresponding inter-species protein pairs in the host-parasite system. To reduce the number of spurious predictions, our approach uses either the parasites predicted secretome and membrane proteins or only the secretome depending on whether they are uni-or multicellular respectively. Besides, the host proteome is filtered for proteins expressed in selected cellular localizations and tissues supporting the parasites growth. We evaluated the inferred interactions by analyzing the enriched biological processes and pathways in the predicted networks and their association to known parasitic invasion and evasion mechanisms. The resulting PPI networks were compared across parasites to identify common mechanisms that may define a global pathogenic hallmark. The predicted PPI networks can be visualized and downloaded at http://orthohpi.jensenlab.org. Author SummaryA protein-protein interaction (PPI) network is a collection of interactions between proteins from one or more organisms. Host-parasite PPIs are key to understanding the biology of different parasitic diseases, since predicting PPIs enable to know more about the parasite invasion, infection and persist. Our understanding of PPIs between host and parasites is still . CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/147868 doi: bioRxiv preprint first posted online 3 very limited, as no many systematic experimental studies have so far been performed.Efficacy of treatments for parasitic diseases is limited and in many cases parasites evolve resistance. Thus, there is an urgent need to develop novel drugs or vaccines for these neglected diseases, and thus interest in the functions and interactions of proteins associated with parasitism processes. Here we developed an in silico method to shed light on the interactome in twelve human parasites by combining an orthology based strategy and integrating, domain-domain interaction data, sub-cellular localization and to give a spatial context, we only took in to account those human tissues that support the parasite´s tropism.Here we show that is possible to identify relevant interactions across different parasites and their human h...

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“…The probability of finding specific biomarkers of infection very much increases with potent analytical proteomics tools used in a comprehensive and systematic approach. Advances in MS and protein identification have made possible identification and quantification of levels of cellular proteins in response to dengue virus infection [94]. Previously, the differential protein expression in serum samples from dengue-infected patients resulted in the identification of cellular proteins with potential to become targets in dengue pathogenesis [95,96].…”

Section: Future Perspectivementioning

confidence: 99%

Dengue Laboratory Diagnosis: Still Some Room for Improvement

et al. 2015

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Dengue is the most important and widely distributed arthropod-borne viral disease affecting humans. The number of dengue virus infections has steadily grown and more than 100 countries survey dengue incidence every year. Due to the lack of an approved antiviral treatment or licensed preventative vaccine, accurate and opportune diagnosis is commended for efficient dengue epidemiological surveillance, to propose control measures in order to curtail outbreaks timely and treat patients satisfactorily. In this review, the basis, application and indications for different diagnostic tests are described, and their advantages and limitations considered. At the end of this piece, we speculate what the future may hold for the diagnosis of dengue infections. KeywordsThe four serotypes of dengue virus (DENV 1-4) may equally be the cause of dengue infection in humans. DENV is a member of the Flaviviridae family, genus Flavivirus and is transmitted by the bite of female mosquitoes of the Aedes genus, mainly Aedes aegypti; an anthropophilic arthropod extensively distributed [1,2]. The viral genome is constituted by a single RNA strand of positive polarity of approximately 11 kb. It encodes three structural proteins: the envelope (E), pre-membrane/membrane (prM/M) and capsid (C) proteins; and seven nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5), which are implicated in viral translation, replication and modulation of the host immune response [2,3]. Dengue prevails in 128 countries and it is estimated that more than 2.5 billion people (two fifths of the world's population) are at risk of DENV infection [1,2]. Every year over 50 million DENV infections occur, causing more than 500,000 severe cases of dengue and resulting in at least 125,000 fatalities. The enormous increase in dengue prevalence observed in the last decades is multifactorial in nature. Unplanned and uncontrolled urbanization caused by the global population growth is associated with the deterioration in water supply quality and poor sewer and waste management systems availability. These conditions are ideal for the domestic propagation of the vector and a hallmark for the most recent epidemic outbreaks observed in tropical regions of the world such as Southeast Asia and South America. In addition, the modern trade globalization facilitates the introduction of the vector and all DENV serotypes to previously uninfected populated centers [1,4,5], where a highly dense susceptible population may be at risk. In this way, over the last decades DENV infection has become a global menace not only for tropical regions of the world, where the vector thrives, but also for temperate zones starting to be colonized by Aedes mosquitoes. The annual cost of dengue disease is estimated at US$135 million in Asiatic countries alone [6].

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High-Throughput Quantitative Proteomic Analysis of Dengue Virus Type 2 Infected A549 Cells

Cited by 58 publications

References 94 publications

Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements

Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements

An integrative method to unravel the host-parasite interactome: an orthology-based approach

Dengue Laboratory Diagnosis: Still Some Room for Improvement

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