{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Manual"},"PMID":{"@attributes":{"Version":"1"},"@text":"20956313"},"DateCompleted":{"Year":"2010","Month":"11","Day":"30"},"DateRevised":{"Year":"2021","Month":"10","Day":"20"},"Article":{"@attributes":{"PubModel":"Print-Electronic"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Electronic"},"@text":"1091-6490"},"JournalIssue":{"@attributes":{"CitedMedium":"Internet"},"Volume":"107","Issue":"44","PubDate":{"Year":"2010","Month":"Nov","Day":"02"}},"Title":"Proceedings of the National Academy of Sciences of the United States of America","ISOAbbreviation":"Proc Natl Acad Sci U S A"},"ArticleTitle":"Mucosal host immune response predicts the severity and duration of herpes simplex virus-2 genital tract shedding episodes.","Pagination":{"StartPage":"18973","EndPage":"18978","MedlinePgn":"18973-8"},"ELocationID":[{"@attributes":{"EIdType":"doi","ValidYN":"Y"},"@text":"10.1073\/pnas.1006614107"}],"Abstract":{"AbstractText":["Herpes simplex virus-2 (HSV-2) shedding episodes in humans vary markedly in duration and virologic titer within an infected person over time, an observation that is unexplained. To evaluate whether host or virological factors more closely accounted for this variability, we combined measures of viral replication and CD8(+) lymphocyte density in genital biopsies, with a stochastic mathematical model of HSV-2 infection. Model simulations reproduced quantities of virus and duration of shedding detected in 1,003 episodes among 386 persons. In the simulations, local CD8(+) lymphocyte density in the mucosa at episode onset predicted peak HSV DNA copy number and whether genital lesions or subclinical shedding occurred. High density of CD8(+) T cells in the mucosa correlated with decreased infected cell lifespan and fewer infected epithelial cells before episode clearance. If infected cell lifespan increased by 15 min because of CD8(+) lymphocyte decay, then there was potential for a thousandfold increase in the number of infected cells. The model suggests that the rate of containment of infected cells by the peripheral mucosal immune system is the major driver of duration and severity of HSV-2 reactivation in the immunocompetent host."]},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Schiffer","ForeName":"Joshua T","Initials":"JT","AffiliationInfo":[{"Affiliation":"Department of Medicine, Laboratory Medicine, Global Health Medicine, University of Washington, Seattle, WA 98195, USA. jschiffe@fhcrc.org"}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Abu-Raddad","ForeName":"Laith","Initials":"L"},{"@attributes":{"ValidYN":"Y"},"LastName":"Mark","ForeName":"Karen E","Initials":"KE"},{"@attributes":{"ValidYN":"Y"},"LastName":"Zhu","ForeName":"Jia","Initials":"J"},{"@attributes":{"ValidYN":"Y"},"LastName":"Selke","ForeName":"Stacy","Initials":"S"},{"@attributes":{"ValidYN":"Y"},"LastName":"Koelle","ForeName":"David M","Initials":"DM"},{"@attributes":{"ValidYN":"Y"},"LastName":"Wald","ForeName":"Anna","Initials":"A"},{"@attributes":{"ValidYN":"Y"},"LastName":"Corey","ForeName":"Lawrence","Initials":"L"}]},"Language":["eng"],"GrantList":{"@attributes":{"CompleteYN":"Y"},"Grant":[{"GrantID":"R37 AI042528","Acronym":"AI","Agency":"NIAID NIH HHS","Country":"United States"},{"GrantID":"T32 AI007140","Acronym":"AI","Agency":"NIAID NIH HHS","Country":"United States"},{"GrantID":"T32 AI07140","Acronym":"AI","Agency":"NIAID NIH HHS","Country":"United States"},{"GrantID":"P01 AI030731","Acronym":"AI","Agency":"NIAID NIH HHS","Country":"United States"},{"GrantID":"T32 CA080416","Acronym":"CA","Agency":"NCI NIH HHS","Country":"United States"},{"GrantID":"K23 AI087206","Acronym":"AI","Agency":"NIAID NIH HHS","Country":"United States"},{"GrantID":"T32 CA80416","Acronym":"CA","Agency":"NCI NIH HHS","Country":"United States"}]},"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D016428"},"@text":"Journal Article"},{"@attributes":{"UI":"D052061"},"@text":"Research Support, N.I.H., Extramural"},{"@attributes":{"UI":"D013485"},"@text":"Research Support, Non-U.S. Gov't"}]},"ArticleDate":[{"@attributes":{"DateType":"Electronic"},"Year":"2010","Month":"10","Day":"18"}]},"MedlineJournalInfo":{"Country":"United States","MedlineTA":"Proc Natl Acad Sci U S A","NlmUniqueID":"7505876","ISSNLinking":"0027-8424"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D004279"},"@text":"DNA, Viral"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D001706","MajorTopicYN":"N"},"@text":"Biopsy"}},{"DescriptorName":{"@attributes":{"UI":"D018414","MajorTopicYN":"N"},"@text":"CD8-Positive T-Lymphocytes"},"QualifierName":[{"@attributes":{"UI":"Q000276","MajorTopicYN":"Y"},"@text":"immunology"},{"@attributes":{"UI":"Q000473","MajorTopicYN":"N"},"@text":"pathology"},{"@attributes":{"UI":"Q000821","MajorTopicYN":"N"},"@text":"virology"}]},{"DescriptorName":{"@attributes":{"UI":"D015331","MajorTopicYN":"N"},"@text":"Cohort Studies"}},{"DescriptorName":{"@attributes":{"UI":"D004279","MajorTopicYN":"N"},"@text":"DNA, Viral"},"QualifierName":[{"@attributes":{"UI":"Q000276","MajorTopicYN":"N"},"@text":"immunology"}]},{"DescriptorName":{"@attributes":{"UI":"D005260","MajorTopicYN":"N"},"@text":"Female"}},{"DescriptorName":{"@attributes":{"UI":"D006558","MajorTopicYN":"N"},"@text":"Herpes Genitalis"},"QualifierName":[{"@attributes":{"UI":"Q000276","MajorTopicYN":"Y"},"@text":"immunology"},{"@attributes":{"UI":"Q000473","MajorTopicYN":"N"},"@text":"pathology"},{"@attributes":{"UI":"Q000821","MajorTopicYN":"N"},"@text":"virology"}]},{"DescriptorName":{"@attributes":{"UI":"D018258","MajorTopicYN":"N"},"@text":"Herpesvirus 2, Human"},"QualifierName":[{"@attributes":{"UI":"Q000502","MajorTopicYN":"Y"},"@text":"physiology"}]},{"DescriptorName":{"@attributes":{"UI":"D054884","MajorTopicYN":"N"},"@text":"Host-Pathogen Interactions"},"QualifierName":[{"@attributes":{"UI":"Q000276","MajorTopicYN":"N"},"@text":"immunology"}]},{"DescriptorName":{"@attributes":{"UI":"D006801","MajorTopicYN":"N"},"@text":"Humans"}},{"DescriptorName":{"@attributes":{"UI":"D018928","MajorTopicYN":"Y"},"@text":"Immunity, Mucosal"}},{"DescriptorName":{"@attributes":{"UI":"D008297","MajorTopicYN":"N"},"@text":"Male"}},{"DescriptorName":{"@attributes":{"UI":"D018448","MajorTopicYN":"Y"},"@text":"Models, Immunological"}},{"DescriptorName":{"@attributes":{"UI":"D009092","MajorTopicYN":"N"},"@text":"Mucous Membrane"},"QualifierName":[{"@attributes":{"UI":"Q000276","MajorTopicYN":"N"},"@text":"immunology"},{"@attributes":{"UI":"Q000473","MajorTopicYN":"N"},"@text":"pathology"},{"@attributes":{"UI":"Q000821","MajorTopicYN":"N"},"@text":"virology"}]},{"DescriptorName":{"@attributes":{"UI":"D014779","MajorTopicYN":"N"},"@text":"Virus Replication"},"QualifierName":[{"@attributes":{"UI":"Q000276","MajorTopicYN":"Y"},"@text":"immunology"}]},{"DescriptorName":{"@attributes":{"UI":"D017201","MajorTopicYN":"N"},"@text":"Virus Shedding"},"QualifierName":[{"@attributes":{"UI":"Q000276","MajorTopicYN":"Y"},"@text":"immunology"}]}]},"CoiStatement":"The authors declare no conflict of interest."},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"entrez"},"Year":"2010","Month":"10","Day":"20","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"pubmed"},"Year":"2010","Month":"10","Day":"20","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"medline"},"Year":"2010","Month":"12","Day":"14","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"pmc-release"},"Year":"2011","Month":"5","Day":"2"}]},"PublicationStatus":"ppublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"20956313"},{"@attributes":{"IdType":"pmc"},"@text":"PMC2973882"},{"@attributes":{"IdType":"doi"},"@text":"10.1073\/pnas.1006614107"},{"@attributes":{"IdType":"pii"},"@text":"1006614107"}]},"ReferenceList":[{"Reference":[{"Citation":"Corey L, Adams HG, Brown ZA, Holmes KK. 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