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Pettersson, U
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Publications (10 of 76) Show all publications
Valdés, A., Zhao, H., Pettersson, U. & Lind, S. B. (2018). Time-resolved proteomics of adenovirus infected cells. PLoS ONE, 13(9), Article ID e0204522.
Open this publication in new window or tab >>Time-resolved proteomics of adenovirus infected cells
2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 9, article id e0204522Article in journal (Refereed) Published
Abstract [en]

Viral infections cause large problems in the world and deeper understanding of the disease mechanisms is needed. Here we present an analytical strategy to investigate the host cell protein changes during human adenovirus type 2 (HAdV-C2 or Ad2) infection of lung fibro-blasts by stable isotope labelling of amino acids in cell culture (SILAC) and nanoLC-MS/MS. This work focuses on early phase of infection (6 and 12 h post-infection (hpi)) but the data is combined with previously published late phase (24 and 36 hpi) proteomics data to produce a time series covering the complete infection. As many as 2169 proteins were quantitatively monitored from 6 to 36 hpi, while some proteins were time-specific. After applying different filter criteria, 2027 and 2150 proteins were quantified at 6 and 12 hpi and among them, 431 and 544 were significantly altered at the two time points. Pathway analysis showed that the De novo purine and pyrimidine biosynthesis, Glycolysis and Cytoskeletal regulation by Rho GTPase pathways were activated early during infection while inactivation of the Integrin signalling pathway started between 6 and 12 hpi. Moreover, upstream regulator analysis predicted MYC to be activated with time of infection and protein and RNA data for genes controlled by this transcription factor showed good correlation, which validated the use of protein data for this prediction. Among the identified phosphorylation sites, a group related to glycolysis and cytoskeletal reorganization were up-regulated during infection. The results show specific aspects on how the host cell proteins, the final products in the genetic information flow, are influenced by Ad2 infection, which would be overlooked if only knowledge derived from mRNA data is considered.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2018
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-363424 (URN)10.1371/journal.pone.0204522 (DOI)000445639700059 ()30252905 (PubMedID)
Funder
Åke Wiberg Foundation, M14-0127Magnus Bergvall Foundation, 2015-01200 2016-01675Carl Tryggers foundation , CST 15:57
Available from: 2018-10-18 Created: 2018-10-18 Last updated: 2018-10-18Bibliographically approved
Gromova, A., Zhao, H., Konzer, A., Falk, A., Pettersson, U. & Bergström Lind, S. (2017). Identification of the adenovirus type 2 C-168 protein. Virus Research, 238, 110-113
Open this publication in new window or tab >>Identification of the adenovirus type 2 C-168 protein
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2017 (English)In: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 238, p. 110-113Article in journal (Refereed) Published
Abstract [en]

A hitherto predicted but undetected protein, C-168, in adenovirus type 2 (Ad2) has been identified using mass spectrometry (MS) based proteomics. The gene of this 17.7 kDa protein is located on the forward strand in the major late transcription unit between base pairs 9294 and 9797. A tryptic peptide, derived from the C-terminal part of the protein, was identified with high amino acid sequence coverage. A candidate splice site for the corresponding mRNA is also presented. The protein sequence is unusual with repeats of serine, glycine and arginine. A bioinformatics prediction of protein function and localization is presented.

Keywords
C-168, Adenovirus type 2, Mass spectrometry, Identification, Sequence comparison
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-334102 (URN)10.1016/j.virusres.2017.06.013 (DOI)000408077500015 ()28629901 (PubMedID)
Funder
Åke Wiberg Foundation, M14-0127Magnus Bergvall Foundation, 2015-01200; 2016-01675Carl Tryggers foundation , CST 15:57
Available from: 2017-11-24 Created: 2017-11-24 Last updated: 2017-12-21
Zhao, H., Konzer, A., Mi, J., Chen, M., Pettersson, U. & Lind, S. B. (2017). Posttranscriptional regulation in adenovirus infected cells. Journal of Proteome Research, 16(2), 872-888
Open this publication in new window or tab >>Posttranscriptional regulation in adenovirus infected cells
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2017 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 16, no 2, p. 872-888Article in journal (Refereed) Published
Abstract [en]

A deeper understanding of how viruses reprogramtheir hosts for production of progeny is needed to combatinfections. Most knowledge on the regulation of cellular geneexpression during adenovirus infection is derived from mRNAstudies. Here, we investigated the changes in protein expressionduring the late phase of adenovirus type 2 (Ad2) infection of theIMR-90 cell line by stable isotope labeling in cell culture withsubsequent liquid chromatography−high resolution tandemmass spectrometric analysis. Two biological replicates of samplescollected at 24 and 36 h post-infection (hpi) were investigated using swapped labeling. In total, 2648 and 2394 proteins werequantified at 24 and 36 hpi, respectively. Among them, 659 and 645 were deregulated >1.6-fold at the two time points. Theprotein expression was compared with RNA expression using cDNA sequencing data. The correlation was surprisingly low(r = 0.3), and several examples of posttranscriptional regulation were observed; e.g., proteins related to carbohydrate metabolismwere up-regulated at the protein level but unchanged at the RNA level, whereas histone proteins were down-regulated at theprotein level but up-regulated at the RNA level. The deregulation of cellular gene expression by adenovirus is mediated atmultiple levels and more complex than hitherto believed.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2017
National Category
Analytical Chemistry Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-311796 (URN)10.1021/acs.jproteome.6b00834 (DOI)000393539600048 ()
Funder
Carl Tryggers foundation Åke Wiberg FoundationMagnus Bergvall Foundation
Available from: 2017-01-02 Created: 2017-01-02 Last updated: 2018-01-13Bibliographically approved
Källsten, M., Gromova, A., Zhao, H., Valdés, A., Konzer, A., Pettersson, U. & Lind, S. B. (2017). Temporal characterization of the non-structural Adenovirus type 2 proteome and phosphoproteome using high-resolving mass spectrometry. Virology, 511, 240-248
Open this publication in new window or tab >>Temporal characterization of the non-structural Adenovirus type 2 proteome and phosphoproteome using high-resolving mass spectrometry
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2017 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 511, p. 240-248Article in journal (Refereed) Published
Abstract [en]

The proteome and phosphoproteome of non-structural proteins of Adenovirus type 2 (Ad2) were time resolved using a developed mass spectrometry approach. These proteins are expressed by the viral genome and important for the infection process, but not part of the virus particle. We unambiguously confirm the existence of 95% of the viral proteins predicted to be encoded by the viral genome. Most non-structural proteins peaked in expression at late time post infection. We identified 27 non-redundant sites of phosphorylation on seven different non-structural proteins. The most heavily phosphorylated protein was the DNA binding protein (DBP) with 15 different sites. The phosphorylation occupancy rate could be calculated and monitored with time post infection for 15 phosphorylated sites on various proteins. In the DBP, phosphorylations with time-dependent relation were observed. The findings show the complexity of the Ad2 non-structural proteins and opens up a discussion for potential new drug targets.

Place, publisher, year, edition, pages
Uppsala: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2017
Keywords
Adenovirus type 2, Non-structural proteins, Time series, Protein expression, Phosphorylation, Mass spectrometry
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-337189 (URN)10.1016/j.virol.2017.08.032 (DOI)000412791500027 ()28915437 (PubMedID)
Funder
Åke Wiberg Foundation, M14-0127Magnus Bergvall Foundation, 2015-01200, 2016-01675Carl Tryggers foundation , CST 15:57
Available from: 2017-12-21 Created: 2017-12-21 Last updated: 2018-01-02Bibliographically approved
Chen, M., Hongxing, Z., Bergström Lind, S. & Pettersson, U. (2016). Data on the expression of cellular lncRNAs in human adenovirus infected cells. Data in Brief, 8, 1263-1279
Open this publication in new window or tab >>Data on the expression of cellular lncRNAs in human adenovirus infected cells
2016 (English)In: Data in Brief, E-ISSN 2352-3409, Vol. 8, p. 1263-1279Article in journal (Refereed) Published
Abstract [en]

Expression of cellular long non-coding RNAs (lncRNAs) in human primary lung fibroblasts (IMR-90) during the course of adenovirus type 2 (Ad2) infection was studied by strand-specific whole transcriptome sequencing. In total, 645 cellular lncRNAs were expressed at a significant level and 398 of them were changed more than 2-fold. The changes in expression followed a distinct temporal pattern. Significantly, 80% of the changes occurred at the late phase and 80% of the de-regulated lncRNAs were up-regulated. The three largest groups of deregulated lncRNAs were 125 antisense RNAs, 111 pseudogenes and 85 long intergenic non-coding RNAs (lincRNAs). Lastly, more than 36% of lncRNAs have been shown to interact with RNA binding proteins.

Place, publisher, year, edition, pages
Elsevier: , 2016
Keywords
Adenovirus;Long noncodingRNA;IncRNA; IMR90
National Category
Medical Genetics
Research subject
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-301964 (URN)10.1016/j.dib.2016.06.053 (DOI)27547808 (PubMedID)
Funder
Magnus Bergvall Foundation, 2015-01200Åke Wiberg Foundation
Available from: 2016-08-26 Created: 2016-08-26 Last updated: 2018-02-12Bibliographically approved
Zhao, H., Chen, M., Bergström Lind, S. & Pettersson, U. (2016). Distinct temporal changes in host cell lncRNA expression during the course of an adenovirus infection. Virology, 492, 242-250
Open this publication in new window or tab >>Distinct temporal changes in host cell lncRNA expression during the course of an adenovirus infection
2016 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 492, p. 242-250Article in journal (Refereed) Published
Abstract [en]

The deregulation of cellular long non-coding RNA (lncRNA) expression during a human adenovirus infection was studied by deep sequencing. Expression of lncRNAs increased substantially following the progression of the infection. Among 645 significantly expressed lncRNAs, the expression of 398 was changed more than 2-fold. More than 80% of them were up-regulated and 80% of them were detected during the late phase. Eased on the genomic locations of the deregulated lncRNAs in relation to known mRNAs and miRNAs, they were predicted to be involved in growth, structure, apoptosis and wound healing in the early phase, cell proliferation in the intermediate phase and protein synthesis, modification and transport in the late phase. The most significant functions of cellular RNA-binding proteins, previously shown to interact with the deregulated lncRNAs identified here, are involved in RNA splicing, nuclear export and translation events. We hypothesize that adenoviruses exploit the lncRNA network to optimize their reproduction.

Keywords
Long non-coding RNA (lncRNA); Antisense RNAs; Cellular gene expression; Adenovirus infection; RNA sequencing; RNA-binding proteins (RBPs); lncRNA expression profile
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-284507 (URN)10.1016/j.virol.2016.02.017 (DOI)000374209900027 ()27003248 (PubMedID)
Funder
Magnus Bergvall FoundationÅke Wiberg Foundation
Available from: 2016-04-18 Created: 2016-04-18 Last updated: 2018-01-10Bibliographically approved
Zhao, H., Chen, M., Tellgren-Roth, C. & Pettersson, U. (2015). Fluctuating expression of microRNAs in adenovirus infected cells. Virology, 478, 99-111
Open this publication in new window or tab >>Fluctuating expression of microRNAs in adenovirus infected cells
2015 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 478, p. 99-111Article in journal (Refereed) Published
Abstract [en]

The changes in cellular microRNA (miRNA) expression during the course of an adenovirus type 2 infection in human lung fibroblast were studied by deep RNA sequencing. Expressions of 175 miRNAs with over 100 transcripts per million nucleotides were changed more than 1.5-fold. The expression patterns of these miRNAs changed dramatically during the course of the infection, from upregulation of the miRNAs known as tumor suppressors (such as miR-22, miR-320, let-7, miR-181b, and miR-155) and down-regulation of oncogenic miRNAs (such as miR-21 and miR-31) early to downregulation of tumor suppressor miRNAs (such as let-7 family, mir-30 family, 23/27 cluster) and upregulation of oncogenic miRNAs (include miR-125, miR-27, miR-191) late after infection. The switch in miRNA expression pattern occurred when adenovirus DNA replication started. Furthermore, deregulation of cellular miRNA expression was a step-wise and special sets of miRNAs were deregulated in different phases of infection.

Keywords
Adenovirus infection, Cellular microRNA, Deep sequencing, Expression profile
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-251992 (URN)10.1016/j.virol.2015.01.033 (DOI)000352116800010 ()25744056 (PubMedID)
Available from: 2015-05-11 Created: 2015-04-28 Last updated: 2018-01-11Bibliographically approved
Zhao, H., Chen, M. & Pettersson, U. (2014). A new look at adenovirus splicing. Virology, 456, 329-341
Open this publication in new window or tab >>A new look at adenovirus splicing
2014 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 456, p. 329-341Article in journal (Refereed) Published
Abstract [en]

Adenovirus type 2 RNA splicing events were quantitatively mapped by using deep cDNA sequencing. The majority of the previously identified splice sites were detected. The lack of complete consistency between the present and previous results is because of some sites which were incorrectly mapped in previous studies, such as the splice sites for pVII, pVIII and E3-11.6K. Several previously predicted splice sites such as that for E3-14.5K and E4ORF3/4 were not detected. In addition, several new splice sites were identified. The novel RNAs may code for hitherto undetected proteins or alternatively spliced mRNAs for known proteins. The open reading frames downstream of two novel splice sites, located in the major late transcription unit region, were shown to be highly conserved. Another interesting possibility is that some of them are non-coding RNAs. Finally, the adenovirus mRNA polyadenylation sites were accurately mapped and in some cases shown to be heterogeneous.

Keywords
Adenovirus type 2 infection, RNA splicing, Polyadenylation, cDNA sequencing
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-228561 (URN)10.1016/j.virol.2014.04.006 (DOI)000337258600033 ()
Available from: 2014-07-17 Created: 2014-07-16 Last updated: 2018-01-11Bibliographically approved
Elfineh, L., Classon, C., Asplund, A., Pettersson, U., Kamali-Moghaddam, M. & Lind, S. B. (2014). Tyrosine phosphorylation profiling via in situ proximity ligation assay. BMC Cancer, 14, 435
Open this publication in new window or tab >>Tyrosine phosphorylation profiling via in situ proximity ligation assay
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2014 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, p. 435-Article in journal (Refereed) Published
Abstract [en]

Background: Tyrosine phosphorylation (pTyr) is an important cancer relevant posttranslational modification since it regulates protein activity and cellular localization. By controlling cell growth and differentiation it plays an important role in tumor development. This paper describes a novel approach for detection and visualization of a panel of pTyr proteins in tumors using in situ proximity ligation assay. Methods: K562 leukemia cells were treated with tyrosine kinase and/or phosphatase inhibitors to induce differences in pTyr levels and mimic cells with different malignant properties. Cells were then probed with one antibody against the pTyr modification and another probe against the detected protein, resulting in a detectable fluorescent signal once the probes were in proximity. Results: Total and protein specific pTyr levels on ABL, SHC, ERK2 and PI3K proteins were detected and samples of control and treated cells were distinguished at the pTyr level using this novel approach. Promising results were also detected for formalin fixed and paraffin embedded cells in the micro array format. Conclusions: This application of in situ proximity ligation assay is valuable in order to study the pTyr modification of a panel of proteins in large data sets to validate mass spectrometric data and to be combined with tissue microarrays. The approach offers new opportunities to reveal the pTyr signatures in cells of different malignant properties that can be used as biomarker of disease in the future.

Keywords
Cancer biomarkers, Protein signaling, Protein tyrosine phosphorylation, in situ proximity ligation assay (in situ PLA)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-229297 (URN)10.1186/1471-2407-14-435 (DOI)000338162100001 ()
Available from: 2014-08-06 Created: 2014-08-05 Last updated: 2017-12-05Bibliographically approved
Zhao, H., Chen, M. & Pettersson, U. (2013). Identification of adenovirus-encoded small RNAs by deep RNA sequencing. Virology, 442(2), 148-155
Open this publication in new window or tab >>Identification of adenovirus-encoded small RNAs by deep RNA sequencing
2013 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 442, no 2, p. 148-155Article in journal (Refereed) Published
Abstract [en]

Using deep RNA sequencing, we have studied the expression of adenovirus-encoded small RNAs at different times after infection. Nineteen small RNAs which comprised more than 1% of the total pool of small RNAs at least one time point were identified. These small RNAs were between 25 and 35 nucleotides long and mapped in the region of the VA RNAI and RNAII genes. However, the overlap was incomplete and some contained a few extra nucleotides at the 3' end. This finding together with the observation that some of the small RNAs were detected before VA RNA expression had started might indicate that they are derived from other precursors than VA RNAI and II. Interestingly, the small RNAs displayed different expression profiles during the course of the infection suggesting that they have different functions. An effort was made to identify their mRNA targets by using computer prediction and deep cDNA sequencing. The most significant targets for the earliest small RNAs were genes involved in signaling pathways. 

Keywords
Adenovirus-encoded small RNA, RNA sequencing, Small RNA target prediction, Suppression of cellular gene expression, Viral defense mechanism
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-204770 (URN)10.1016/j.virol.2013.04.006 (DOI)000321072600006 ()
Available from: 2013-08-15 Created: 2013-08-12 Last updated: 2017-12-06Bibliographically approved
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