cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells
Publication Date
April 08, 2016
Journal
PLOS Pathogens
Authors
Jennifer Paijo, Marius Döring, Julia Spanier, Elena Grabski, et al
Volume
12
Issue
4
Pages
e1005546
DOI
https://dx.plos.org/10.1371/journal.ppat.1005546
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005546
Web of Science
000378156900031
Scopus
84964850345
Mendeley
http://www.mendeley.com/research/cgas-senses-human-cytomegalovirus-induces-type-i-interferon-responses-human-monocytederived-cells
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Mendeley | Further Information

{"title"=>"cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Jennifer", "last_name"=>"Paijo", "scopus_author_id"=>"56668748100"}, {"first_name"=>"Marius", "last_name"=>"Döring", "scopus_author_id"=>"56079865800"}, {"first_name"=>"Julia", "last_name"=>"Spanier", "scopus_author_id"=>"56421870600"}, {"first_name"=>"Elena", "last_name"=>"Grabski", "scopus_author_id"=>"36537044200"}, {"first_name"=>"Mohammed", "last_name"=>"Nooruzzaman", "scopus_author_id"=>"24468767300"}, {"first_name"=>"Tobias", "last_name"=>"Schmidt", "scopus_author_id"=>"57199319722"}, {"first_name"=>"Gregor", "last_name"=>"Witte", "scopus_author_id"=>"57198208751"}, {"first_name"=>"Martin", "last_name"=>"Messerle", "scopus_author_id"=>"7004636907"}, {"first_name"=>"Veit", "last_name"=>"Hornung", "scopus_author_id"=>"6603665800"}, {"first_name"=>"Volkhard", "last_name"=>"Kaever", "scopus_author_id"=>"7004018370"}, {"first_name"=>"Ulrich", "last_name"=>"Kalinke", "scopus_author_id"=>"16207392500"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"pmid"=>"27058035", "doi"=>"10.1371/journal.ppat.1005546", "sgr"=>"84964850345", "isbn"=>"10.1371/journal.ppat.1005546", "scopus"=>"2-s2.0-84964850345", "issn"=>"15537374", "pui"=>"610217044"}, "id"=>"befa9e98-8449-3fde-ad23-b3f9894e16d1", "abstract"=>"Human cytomegalovirus (HCMV) infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS) senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING) and thus induces antiviral type I interferon (IFN-I) responses. We found that plasmacytoid dendritic cells (pDC) as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages.", "link"=>"http://www.mendeley.com/research/cgas-senses-human-cytomegalovirus-induces-type-i-interferon-responses-human-monocytederived-cells", "reader_count"=>56, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>4, "Student > Doctoral Student"=>5, "Researcher"=>9, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>4, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>7, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>4, "Student > Doctoral Student"=>5, "Researcher"=>9, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>4, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>7, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>20, "Medicine and Dentistry"=>6, "Chemical Engineering"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>15}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>15}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>20}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>5}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "reader_count_by_country"=>{"United States"=>1, "France"=>1}, "group_count"=>2}

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Scopus | Further Information

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