Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction
Publication Date
February 27, 2017
Authors
Ekaterina Maidji, Ma Somsouk, Jose M. Rivera, Peter W. Hunt, et al
Volume
13
Issue
2
Pages
e1006202
DOI
https://dx.plos.org/10.1371/journal.ppat.1006202
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1006202
Scopus
85014128064
Mendeley
http://www.mendeley.com/research/replication-cmv-gut-hivinfected-individuals-epithelial-barrier-dysfunction
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Mendeley | Further Information

{"title"=>"Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction", "type"=>"journal", "authors"=>[{"first_name"=>"Ekaterina", "last_name"=>"Maidji", "scopus_author_id"=>"6603285856"}, {"first_name"=>"Ma", "last_name"=>"Somsouk", "scopus_author_id"=>"24339287200"}, {"first_name"=>"Jose M.", "last_name"=>"Rivera", "scopus_author_id"=>"57193446937"}, {"first_name"=>"Peter W.", "last_name"=>"Hunt", "scopus_author_id"=>"7202324398"}, {"first_name"=>"Cheryl A.", "last_name"=>"Stoddart", "scopus_author_id"=>"7003911238"}], "year"=>2017, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "scopus"=>"2-s2.0-85014128064", "pmid"=>"28241080", "doi"=>"10.1371/journal.ppat.1006202", "pui"=>"614624771", "isbn"=>"1111111111", "sgr"=>"85014128064"}, "id"=>"e34e6037-187f-348a-b142-a2ac280460ee", "abstract"=>"Although invasive cytomegalovirus {(CMV)} disease is uncommon in the era of antiretroviral therapy {(ART),} asymptomatic {CMV} coinfection is nearly ubiquitous in {HIV} infected individuals. While microbial translocation and gut epithelial barrier dysfunction may promote persistent immune activation in treated {HIV} infection, potentially contributing to morbidity and mortality, it has been unclear whether {CMV} replication in individuals with no symptoms of {CMV} disease might play a role in this process. We hypothesized that persistent {CMV} replication in the intestinal epithelium of {HIV/CMV-coinfected} individuals impairs gut epithelial barrier function. Using a combination of state-of-the-art in situ hybridization technology {(RNAscope)} and immunohistochemistry, we detected {CMV} {DNA} and proteins and evidence of intestinal damage in rectosigmoid samples from {CMV-positive} individuals with both untreated and {ART-suppressed} {HIV} infection. Two different model systems, primary human intestinal cells differentiated in vitro to form polarized monolayers and a humanized mouse model of human gut, together demonstrated that intestinal epithelial cells are fully permissive to {CMV} replication. Independent of {HIV,} {CMV} disrupted tight junctions of polarized intestinal cells, significantly reducing transepithelial electrical resistance, a measure of monolayer integrity, and enhancing transepithelial permeability. The effect of {CMV} infection on the intestinal epithelium is mediated, at least in part, by the {CMV-induced} proinflammatory cytokine {IL-6.} Furthermore, letermovir, a novel {anti-CMV} drug, dampened the effects of {CMV} on the epithelium. Together, our data strongly suggest that {CMV} can disrupt epithelial junctions, leading to bacterial translocation and chronic inflammation in the gut and that {CMV} could serve as a target for therapeutic intervention to prevent or treat gut epithelial barrier dysfunction during {HIV} infection.", "link"=>"http://www.mendeley.com/research/replication-cmv-gut-hivinfected-individuals-epithelial-barrier-dysfunction", "reader_count"=>15, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>2, "Design"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>1}

Scopus | Further Information

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