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dc.contributor.authorWeiss, Eric R.
dc.contributor.authorAlter, Galit
dc.contributor.authorOgembo, Javier Gordon
dc.contributor.authorHenderson, Jennifer L.
dc.contributor.authorTabak, Barbara
dc.contributor.authorBakis, Yasin
dc.contributor.authorSomasundaran, Mohan
dc.contributor.authorGarber, Manuel
dc.contributor.authorSelin, Liisa K.
dc.contributor.authorLuzuriaga, Katherine
dc.date2022-08-11T08:08:36.000
dc.date.accessioned2022-08-23T16:01:04Z
dc.date.available2022-08-23T16:01:04Z
dc.date.issued2016-12-16
dc.date.submitted2018-07-18
dc.identifier.citation<p>J Virol. 2016 Dec 16;91(1). pii: e01562-16. Print 2017 Jan 1. <a href="https://doi.org/10.1128/JVI.01562-16">Link to article on publisher's site</a></p>
dc.identifier.issn0022-538X (Linking)
dc.identifier.doi10.1128/JVI.01562-16
dc.identifier.pmid27733645
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31035
dc.description.abstractThe Epstein-Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis [AIM]) and again 6 months later (during convalescence [CONV]). EBV gp350-specific IgG was detected in the sera of 17 (71%) of 24 individuals at the time of AIM and all 24 (100%) individuals during CONV; binding antibody titers increased from AIM through CONV, reaching levels equivalent to those in age-matched, chronically infected individuals. Antibody-dependent cell-mediated phagocytosis (ADCP) was rarely detected during AIM (4 of 24 individuals; 17%) but was commonly detected during CONV (19 of 24 individuals; 79%). The majority (83%) of samples taken during AIM neutralized infection of primary B cells; all samples obtained at 6 months postdiagnosis neutralized EBV infection of cultured and primary target cells. Deep sequencing revealed interpatient gp350 sequence variation but conservation of the CR2-binding site. The levels of gp350-specific neutralizing activity directly correlated with higher peripheral blood EBV DNA levels during AIM and a greater evolution of diversity in gp350 nucleotide sequences from AIM to CONV. In summary, we conclude that the viral load and EBV gp350 diversity during early infection are associated with the development of neutralizing antibody responses following AIM. IMPORTANCE: Antibodies against viral surface proteins can blunt the spread of viral infection by coating viral particles, mediating uptake by immune cells, or blocking interaction with host cell receptors, making them a desirable component of a sterilizing vaccine. The EBV surface protein gp350 is a major target for antibodies. We report the detection of EBV gp350-specific antibodies capable of neutralizing EBV infection in vitro The majority of gp350-directed vaccines focus on glycoproteins from lab-adapted strains, which may poorly reflect primary viral envelope diversity. We report some of the first primary gp350 sequences, noting that the gp350 host receptor binding site is remarkably stable across patients and time. However, changes in overall gene diversity were detectable during infection. Patients with higher peripheral blood viral loads in primary infection and greater changes in viral diversity generated more efficient antibodies. Our findings provide insight into the generation of functional antibodies, necessary for vaccine development.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27733645&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165192/
dc.rightsCopyright © 2016, American Society for Microbiology. Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
dc.subjectADCP
dc.subjectEBV
dc.subjectEpstein-Barr virus
dc.subjectantibodies
dc.subjectgp350
dc.subjectneutralization
dc.subjectBioinformatics
dc.subjectCarbohydrates
dc.subjectComputational Biology
dc.subjectGenomics
dc.subjectHemic and Lymphatic Diseases
dc.subjectImmunology of Infectious Disease
dc.subjectMolecular Biology
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.subjectVirology
dc.subjectVirus Diseases
dc.subjectViruses
dc.titleHigh Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis
dc.typeJournal Article
dc.source.journaltitleJournal of virology
dc.source.volume91
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1002&amp;context=garber_lab_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/garber_lab_pubs/3
dc.identifier.contextkey12504415
refterms.dateFOA2022-08-23T16:01:04Z
html.description.abstract<p>The Epstein-Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and the evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis [AIM]) and again 6 months later (during convalescence [CONV]). EBV gp350-specific IgG was detected in the sera of 17 (71%) of 24 individuals at the time of AIM and all 24 (100%) individuals during CONV; binding antibody titers increased from AIM through CONV, reaching levels equivalent to those in age-matched, chronically infected individuals. Antibody-dependent cell-mediated phagocytosis (ADCP) was rarely detected during AIM (4 of 24 individuals; 17%) but was commonly detected during CONV (19 of 24 individuals; 79%). The majority (83%) of samples taken during AIM neutralized infection of primary B cells; all samples obtained at 6 months postdiagnosis neutralized EBV infection of cultured and primary target cells. Deep sequencing revealed interpatient gp350 sequence variation but conservation of the CR2-binding site. The levels of gp350-specific neutralizing activity directly correlated with higher peripheral blood EBV DNA levels during AIM and a greater evolution of diversity in gp350 nucleotide sequences from AIM to CONV. In summary, we conclude that the viral load and EBV gp350 diversity during early infection are associated with the development of neutralizing antibody responses following AIM.</p> <p>IMPORTANCE: Antibodies against viral surface proteins can blunt the spread of viral infection by coating viral particles, mediating uptake by immune cells, or blocking interaction with host cell receptors, making them a desirable component of a sterilizing vaccine. The EBV surface protein gp350 is a major target for antibodies. We report the detection of EBV gp350-specific antibodies capable of neutralizing EBV infection in vitro The majority of gp350-directed vaccines focus on glycoproteins from lab-adapted strains, which may poorly reflect primary viral envelope diversity. We report some of the first primary gp350 sequences, noting that the gp350 host receptor binding site is remarkably stable across patients and time. However, changes in overall gene diversity were detectable during infection. Patients with higher peripheral blood viral loads in primary infection and greater changes in viral diversity generated more efficient antibodies. Our findings provide insight into the generation of functional antibodies, necessary for vaccine development.</p>
dc.identifier.submissionpathgarber_lab_pubs/3
dc.contributor.departmentGarber Lab
dc.contributor.departmentDepartment of Pathology
dc.contributor.departmentProgram in Bioinformatics and Integrative Biology
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases And Immunology
dc.contributor.departmentProgram in Molecular Medicine


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