Intrafamilial transmission of human cytomegalovirus (HCMV): Long-term dynamics of epitope-specific antibody response in context of avidity maturation
Abstract Background The role of a special early family formation (PEKiP® ), which is popular in Germany, as a potential origin of HCMV-transmission to seronegative mothers is not documented. Objectives To describe the clinical courses, to identify the virological origin and to evaluate a new tool fo...
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| Veröffentlicht in: | Journal of clinical virology 2014-06, Vol.60 (2), p.119-126 |
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| creator | Hamprecht, Klaus Bissinger, Alfred Lennart Arellano-Galindo, Jose Schweinzer, Katrin Jiang, Xioajing Göhring, Katharina Mikeler, Elfriede Jahn, Gerhard |
| description | Abstract Background The role of a special early family formation (PEKiP® ), which is popular in Germany, as a potential origin of HCMV-transmission to seronegative mothers is not documented. Objectives To describe the clinical courses, to identify the virological origin and to evaluate a new tool for diagnosis of a cascade of intrafamilial HCMV primary infections. Study design This prospectively analyzed long-term course of HCMV primary infection leading to hospitalization of two family members, included the evaluation of different IgG/IgM/IgG avidity-assays with an epitope-specific recombinant immunoblot-assay. Additionally, neutralization (NT) assays using fibroblast-and epithelial-target cells were performed to correlate NT50 values to avidity maturation. HCMV gN/gO/gB-RFLP-genotyping and phylogenetic analyses were performed using urine viral isolates. Results The clinical courses of the sequentially occurring intrafamilial HCMV primary infections were unusual, leading to hospitalization. Long-term-serology of the mother revealed concordant results for an unimodal IgG-course and a rapid decrease of IgM-indices from week 7 to week 21 p.i. Interestingly, the cut-off definitions for low and high avidity ranged discordantly from 15 to 25 weeks, and from 18 to 42 weeks p.i., respectively. A good correlation was found between the increase of fibroblast-adapted NT50 values and the appearance of high avidity using the epitope-specific immunoblot (>18 weeks p.i.). RFLP-genotyping and sequencing could identify the index patient as member of PEKiP® -meetings. Conclusions PEKiP® -meetings with naked babies may be an important source of horizontal HCMV-transmission to seronegative pregnant mothers in Germany. Using epitope-specific immunoblots, persisting HCMVp150-IgM-reactivities and good concordance between high IgG-avidity and increase of fibroblast adapted neutralization capacity were found. |
| doi_str_mv | 10.1016/j.jcv.2014.03.006 |
| format | Article |
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Objectives To describe the clinical courses, to identify the virological origin and to evaluate a new tool for diagnosis of a cascade of intrafamilial HCMV primary infections. Study design This prospectively analyzed long-term course of HCMV primary infection leading to hospitalization of two family members, included the evaluation of different IgG/IgM/IgG avidity-assays with an epitope-specific recombinant immunoblot-assay. Additionally, neutralization (NT) assays using fibroblast-and epithelial-target cells were performed to correlate NT50 values to avidity maturation. HCMV gN/gO/gB-RFLP-genotyping and phylogenetic analyses were performed using urine viral isolates. Results The clinical courses of the sequentially occurring intrafamilial HCMV primary infections were unusual, leading to hospitalization. Long-term-serology of the mother revealed concordant results for an unimodal IgG-course and a rapid decrease of IgM-indices from week 7 to week 21 p.i. Interestingly, the cut-off definitions for low and high avidity ranged discordantly from 15 to 25 weeks, and from 18 to 42 weeks p.i., respectively. A good correlation was found between the increase of fibroblast-adapted NT50 values and the appearance of high avidity using the epitope-specific immunoblot (>18 weeks p.i.). RFLP-genotyping and sequencing could identify the index patient as member of PEKiP® -meetings. Conclusions PEKiP® -meetings with naked babies may be an important source of horizontal HCMV-transmission to seronegative pregnant mothers in Germany. Using epitope-specific immunoblots, persisting HCMVp150-IgM-reactivities and good concordance between high IgG-avidity and increase of fibroblast adapted neutralization capacity were found.</description><identifier>ISSN: 1386-6532</identifier><identifier>EISSN: 1873-5967</identifier><identifier>DOI: 10.1016/j.jcv.2014.03.006</identifier><identifier>PMID: 24742599</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Allergy and Immunology ; Antibodies, Viral - blood ; Antibody Affinity ; Avidity ; CMV ; Cytomegalovirus - classification ; Cytomegalovirus - genetics ; Cytomegalovirus - immunology ; Cytomegalovirus - isolation & purification ; Cytomegalovirus Infections - transmission ; Disease Transmission, Infectious ; DNA, Viral - genetics ; Epitopes - immunology ; Family Health ; Female ; Genotype ; Germany ; gO sequencing ; Horizontal transmission ; Human cytomegalovirus ; Humans ; Immunoblot ; Immunoblotting ; Infant, Newborn ; Infectious Disease ; Male ; Middle Aged ; Neutralization Tests ; Polymorphism, Restriction Fragment Length ; Pregnancy ; Primary infection ; Prospective Studies</subject><ispartof>Journal of clinical virology, 2014-06, Vol.60 (2), p.119-126</ispartof><rights>Elsevier B.V.</rights><rights>2014 Elsevier B.V.</rights><rights>Copyright © 2014 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-913d75e091654d85af4b3c3558aaace8b4009ad133f653c4a550e6c68f57c3423</citedby><cites>FETCH-LOGICAL-c441t-913d75e091654d85af4b3c3558aaace8b4009ad133f653c4a550e6c68f57c3423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jcv.2014.03.006$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24742599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hamprecht, Klaus</creatorcontrib><creatorcontrib>Bissinger, Alfred Lennart</creatorcontrib><creatorcontrib>Arellano-Galindo, Jose</creatorcontrib><creatorcontrib>Schweinzer, Katrin</creatorcontrib><creatorcontrib>Jiang, Xioajing</creatorcontrib><creatorcontrib>Göhring, Katharina</creatorcontrib><creatorcontrib>Mikeler, Elfriede</creatorcontrib><creatorcontrib>Jahn, Gerhard</creatorcontrib><title>Intrafamilial transmission of human cytomegalovirus (HCMV): Long-term dynamics of epitope-specific antibody response in context of avidity maturation</title><title>Journal of clinical virology</title><addtitle>J Clin Virol</addtitle><description>Abstract Background The role of a special early family formation (PEKiP® ), which is popular in Germany, as a potential origin of HCMV-transmission to seronegative mothers is not documented. Objectives To describe the clinical courses, to identify the virological origin and to evaluate a new tool for diagnosis of a cascade of intrafamilial HCMV primary infections. Study design This prospectively analyzed long-term course of HCMV primary infection leading to hospitalization of two family members, included the evaluation of different IgG/IgM/IgG avidity-assays with an epitope-specific recombinant immunoblot-assay. Additionally, neutralization (NT) assays using fibroblast-and epithelial-target cells were performed to correlate NT50 values to avidity maturation. HCMV gN/gO/gB-RFLP-genotyping and phylogenetic analyses were performed using urine viral isolates. Results The clinical courses of the sequentially occurring intrafamilial HCMV primary infections were unusual, leading to hospitalization. Long-term-serology of the mother revealed concordant results for an unimodal IgG-course and a rapid decrease of IgM-indices from week 7 to week 21 p.i. Interestingly, the cut-off definitions for low and high avidity ranged discordantly from 15 to 25 weeks, and from 18 to 42 weeks p.i., respectively. A good correlation was found between the increase of fibroblast-adapted NT50 values and the appearance of high avidity using the epitope-specific immunoblot (>18 weeks p.i.). RFLP-genotyping and sequencing could identify the index patient as member of PEKiP® -meetings. Conclusions PEKiP® -meetings with naked babies may be an important source of horizontal HCMV-transmission to seronegative pregnant mothers in Germany. Using epitope-specific immunoblots, persisting HCMVp150-IgM-reactivities and good concordance between high IgG-avidity and increase of fibroblast adapted neutralization capacity were found.</description><subject>Adult</subject><subject>Allergy and Immunology</subject><subject>Antibodies, Viral - blood</subject><subject>Antibody Affinity</subject><subject>Avidity</subject><subject>CMV</subject><subject>Cytomegalovirus - classification</subject><subject>Cytomegalovirus - genetics</subject><subject>Cytomegalovirus - immunology</subject><subject>Cytomegalovirus - isolation & purification</subject><subject>Cytomegalovirus Infections - transmission</subject><subject>Disease Transmission, Infectious</subject><subject>DNA, Viral - genetics</subject><subject>Epitopes - immunology</subject><subject>Family Health</subject><subject>Female</subject><subject>Genotype</subject><subject>Germany</subject><subject>gO sequencing</subject><subject>Horizontal transmission</subject><subject>Human cytomegalovirus</subject><subject>Humans</subject><subject>Immunoblot</subject><subject>Immunoblotting</subject><subject>Infant, Newborn</subject><subject>Infectious Disease</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neutralization Tests</subject><subject>Polymorphism, Restriction Fragment Length</subject><subject>Pregnancy</subject><subject>Primary infection</subject><subject>Prospective Studies</subject><issn>1386-6532</issn><issn>1873-5967</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks1u1DAUhSMEoqXwAGyQl2WRYMc_iUFCQiOglQax4GdreZyb4pDYqe2MyIPwvjiawoIFrHwX3zlXPucWxVOCK4KJeDFUgzlWNSaswrTCWNwrzknb0JJL0dzPM21FKTitz4pHMQ4YE05Z87A4q1nDai7lefHz2qWgez3Z0eoR5dnFycZovUO-R9-WSTtk1uQnuNGjP9qwRHR5tfvw9flLtPfupkwQJtStLluYuGlgtsnPUMYZjO2tQdole_DdigLE2bsIyGZP7xL8SJtAH21n04omnZagU179uHjQ6zHCk7v3ovjy7u3n3VW5__j-evdmXxrGSColoV3DAUsiOOtarnt2oIZy3mqtDbQHhrHUHaG0zykYpjnHIIxoe94Yymp6UVyefOfgbxeISeW_GxhH7cAvURFRN1K0Qor_o7xmlJGWNhklJ9QEH2OAXs3BTjqsimC1FacGlYtTW3EKU5WLy5pnd_bLYYLuj-J3Uxl4dQIg53G0EFQ0FpyBzgYwSXXe_tP-9V9qM1pnjR6_wwpx8EtwOWhFVKwVVp-2y9kOh-QEsWw5_QUH-cAr</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Hamprecht, Klaus</creator><creator>Bissinger, Alfred Lennart</creator><creator>Arellano-Galindo, Jose</creator><creator>Schweinzer, Katrin</creator><creator>Jiang, Xioajing</creator><creator>Göhring, Katharina</creator><creator>Mikeler, Elfriede</creator><creator>Jahn, Gerhard</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>20140601</creationdate><title>Intrafamilial transmission of human cytomegalovirus (HCMV): Long-term dynamics of epitope-specific antibody response in context of avidity maturation</title><author>Hamprecht, Klaus ; Bissinger, Alfred Lennart ; Arellano-Galindo, Jose ; Schweinzer, Katrin ; Jiang, Xioajing ; Göhring, Katharina ; Mikeler, Elfriede ; Jahn, Gerhard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-913d75e091654d85af4b3c3558aaace8b4009ad133f653c4a550e6c68f57c3423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Allergy and Immunology</topic><topic>Antibodies, Viral - blood</topic><topic>Antibody Affinity</topic><topic>Avidity</topic><topic>CMV</topic><topic>Cytomegalovirus - classification</topic><topic>Cytomegalovirus - genetics</topic><topic>Cytomegalovirus - immunology</topic><topic>Cytomegalovirus - isolation & purification</topic><topic>Cytomegalovirus Infections - transmission</topic><topic>Disease Transmission, Infectious</topic><topic>DNA, Viral - genetics</topic><topic>Epitopes - immunology</topic><topic>Family Health</topic><topic>Female</topic><topic>Genotype</topic><topic>Germany</topic><topic>gO sequencing</topic><topic>Horizontal transmission</topic><topic>Human cytomegalovirus</topic><topic>Humans</topic><topic>Immunoblot</topic><topic>Immunoblotting</topic><topic>Infant, Newborn</topic><topic>Infectious Disease</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neutralization Tests</topic><topic>Polymorphism, Restriction Fragment Length</topic><topic>Pregnancy</topic><topic>Primary infection</topic><topic>Prospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hamprecht, Klaus</creatorcontrib><creatorcontrib>Bissinger, Alfred Lennart</creatorcontrib><creatorcontrib>Arellano-Galindo, Jose</creatorcontrib><creatorcontrib>Schweinzer, Katrin</creatorcontrib><creatorcontrib>Jiang, Xioajing</creatorcontrib><creatorcontrib>Göhring, Katharina</creatorcontrib><creatorcontrib>Mikeler, Elfriede</creatorcontrib><creatorcontrib>Jahn, Gerhard</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of clinical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hamprecht, Klaus</au><au>Bissinger, Alfred Lennart</au><au>Arellano-Galindo, Jose</au><au>Schweinzer, Katrin</au><au>Jiang, Xioajing</au><au>Göhring, Katharina</au><au>Mikeler, Elfriede</au><au>Jahn, Gerhard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intrafamilial transmission of human cytomegalovirus (HCMV): Long-term dynamics of epitope-specific antibody response in context of avidity maturation</atitle><jtitle>Journal of clinical virology</jtitle><addtitle>J Clin Virol</addtitle><date>2014-06-01</date><risdate>2014</risdate><volume>60</volume><issue>2</issue><spage>119</spage><epage>126</epage><pages>119-126</pages><issn>1386-6532</issn><eissn>1873-5967</eissn><abstract>Abstract Background The role of a special early family formation (PEKiP® ), which is popular in Germany, as a potential origin of HCMV-transmission to seronegative mothers is not documented. Objectives To describe the clinical courses, to identify the virological origin and to evaluate a new tool for diagnosis of a cascade of intrafamilial HCMV primary infections. Study design This prospectively analyzed long-term course of HCMV primary infection leading to hospitalization of two family members, included the evaluation of different IgG/IgM/IgG avidity-assays with an epitope-specific recombinant immunoblot-assay. Additionally, neutralization (NT) assays using fibroblast-and epithelial-target cells were performed to correlate NT50 values to avidity maturation. HCMV gN/gO/gB-RFLP-genotyping and phylogenetic analyses were performed using urine viral isolates. Results The clinical courses of the sequentially occurring intrafamilial HCMV primary infections were unusual, leading to hospitalization. Long-term-serology of the mother revealed concordant results for an unimodal IgG-course and a rapid decrease of IgM-indices from week 7 to week 21 p.i. Interestingly, the cut-off definitions for low and high avidity ranged discordantly from 15 to 25 weeks, and from 18 to 42 weeks p.i., respectively. A good correlation was found between the increase of fibroblast-adapted NT50 values and the appearance of high avidity using the epitope-specific immunoblot (>18 weeks p.i.). RFLP-genotyping and sequencing could identify the index patient as member of PEKiP® -meetings. Conclusions PEKiP® -meetings with naked babies may be an important source of horizontal HCMV-transmission to seronegative pregnant mothers in Germany. Using epitope-specific immunoblots, persisting HCMVp150-IgM-reactivities and good concordance between high IgG-avidity and increase of fibroblast adapted neutralization capacity were found.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>24742599</pmid><doi>10.1016/j.jcv.2014.03.006</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult Allergy and Immunology Antibodies, Viral - blood Antibody Affinity Avidity CMV Cytomegalovirus - classification Cytomegalovirus - genetics Cytomegalovirus - immunology Cytomegalovirus - isolation & purification Cytomegalovirus Infections - transmission Disease Transmission, Infectious DNA, Viral - genetics Epitopes - immunology Family Health Female Genotype Germany gO sequencing Horizontal transmission Human cytomegalovirus Humans Immunoblot Immunoblotting Infant, Newborn Infectious Disease Male Middle Aged Neutralization Tests Polymorphism, Restriction Fragment Length Pregnancy Primary infection Prospective Studies |
| title | Intrafamilial transmission of human cytomegalovirus (HCMV): Long-term dynamics of epitope-specific antibody response in context of avidity maturation |
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