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description Publicationkeyboard_double_arrow_right Article 2013 CroatiaPublisher:Public Library of Science (PLoS) Funded by:EC | STADVINN, NIH | Bacterial Sepsis and Reac..., NIH | Viral evasion of NK cellsEC| STADVINN ,NIH| Bacterial Sepsis and Reactivation of Latent Cytomegalovirus ,NIH| Viral evasion of NK cellsJuranic Lisnic, Vanda; Babic Cac, Marina; Lisnic, Berislav; Trsan, Tihana; Mefferd, Adam; Das Mukhopadhyay, Chitrangada; Cook, Charles H.; Jonjic, Stipan; Trgovcich, Joanne;Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases. Author Summary We have conducted a comprehensive analysis of the murine cytomegalovirus and host cell transcriptomes during lytic infection. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. Infection alters expression of many unexpected host genes, including many noncoding RNA genes. Correspondingly, many cluster in unexpected biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.
Europe PubMed Centra... arrow_drop_down Europe PubMed CentralArticle . 2013Full-Text: http://europepmc.org/articles/PMC3784481Data sources: PubMed CentralRepository of the University of Rijeka, Faculty of Medicine; Repository of the University of RijekaArticle . 2013License: CC BY NC NDCroatian Scientific Bibliography - CROSBIArticle . 2013Data sources: Croatian Scientific Bibliography - CROSBIadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1371/journal.ppat.1003611&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 75 citations 75 popularity Top 10% influence Top 10% impulse Top 10% Powered by BIP!more_vert Europe PubMed Centra... arrow_drop_down Europe PubMed CentralArticle . 2013Full-Text: http://europepmc.org/articles/PMC3784481Data sources: PubMed CentralRepository of the University of Rijeka, Faculty of Medicine; Repository of the University of RijekaArticle . 2013License: CC BY NC NDCroatian Scientific Bibliography - CROSBIArticle . 2013Data sources: Croatian Scientific Bibliography - CROSBIadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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description Publicationkeyboard_double_arrow_right Article 2013 CroatiaPublisher:Public Library of Science (PLoS) Funded by:EC | STADVINN, NIH | Bacterial Sepsis and Reac..., NIH | Viral evasion of NK cellsEC| STADVINN ,NIH| Bacterial Sepsis and Reactivation of Latent Cytomegalovirus ,NIH| Viral evasion of NK cellsJuranic Lisnic, Vanda; Babic Cac, Marina; Lisnic, Berislav; Trsan, Tihana; Mefferd, Adam; Das Mukhopadhyay, Chitrangada; Cook, Charles H.; Jonjic, Stipan; Trgovcich, Joanne;Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases. Author Summary We have conducted a comprehensive analysis of the murine cytomegalovirus and host cell transcriptomes during lytic infection. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. Infection alters expression of many unexpected host genes, including many noncoding RNA genes. Correspondingly, many cluster in unexpected biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.
Europe PubMed Centra... arrow_drop_down Europe PubMed CentralArticle . 2013Full-Text: http://europepmc.org/articles/PMC3784481Data sources: PubMed CentralRepository of the University of Rijeka, Faculty of Medicine; Repository of the University of RijekaArticle . 2013License: CC BY NC NDCroatian Scientific Bibliography - CROSBIArticle . 2013Data sources: Croatian Scientific Bibliography - CROSBIadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1371/journal.ppat.1003611&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 75 citations 75 popularity Top 10% influence Top 10% impulse Top 10% Powered by BIP!more_vert Europe PubMed Centra... arrow_drop_down Europe PubMed CentralArticle . 2013Full-Text: http://europepmc.org/articles/PMC3784481Data sources: PubMed CentralRepository of the University of Rijeka, Faculty of Medicine; Repository of the University of RijekaArticle . 2013License: CC BY NC NDCroatian Scientific Bibliography - CROSBIArticle . 2013Data sources: Croatian Scientific Bibliography - CROSBIadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.All Research productsarrow_drop_down <script type="text/javascript"> <!-- document.write('<div id="oa_widget"></div>'); document.write('<script type="text/javascript" src="https://www.openaire.eu/index.php?option=com_openaire&view=widget&format=raw&projectId=10.1371/journal.ppat.1003611&type=result"></script>'); --> </script>
For further information contact us at helpdesk@openaire.eu