YEARS

2001-2007

AUTHORS

Frederick C. Wang

TITLE

New World Oncogenic Lymphocryptoviruses

ABSTRACT

DESCRIPTION (provided by applicant): Epstein-Barr virus (EBV) is human gamma herpesvirus in the lymphocryptovirus (LCV) genera and is associated with several types of lymphoid and epithelial cell malignancies. Closely related oncogenic LCV are known to naturally infect Old World nonhuman primate species. However, it was believed that LCV did not naturally infect New World primates and were restricted to humans and Old World primates. We have recently isolated a new herpesvirus, CaIHV-3 (Callithrix herpesvirus 3), from spontaneous B cell lymphomas arising in common marmosets (Callithrix jacchus), a New Wofid primate. Like EBV, Ca1HV-3 infection can immortalize B cells in tissue culture and is persistently endemic in the adult population. We have cloned and sequenced more than 125,000 bp of the genome and have definitively identified it as the first member of the EBV-related LCV genera found in New World primates. Significant differences in the repertoire of lytic and latent infection genes in Ca1HV-3 as compared to EBV and other Old World LCV provide new opportunities for studying the molecular pathogenesis and oncogenesis associated with LCV infection. The occurrence of spontaneous lymphomas in immunocompetent animals is a unique and potentially valuable animal model system for studying LCV-induced malignancies. We will utilize the biologic similarities and genetic differences that have evolved among the human, New World, and Old World LCV to better understand EBV infection and pathogenesis in humans. Specific Aim #1. Complete the Ca1HV-3 primary nucleotide sequence. Specific Aim #2. Functional, biochemical, and genetic analyses of the Ca1HV-3 C3 gene, a positional homologue for the three EBNA-3 genes. Specific aim #3. Study the disease association, epidemiology, and evolution of New World LCV. Specific aim #4. Develop an experimental Ca1HV-3 animal model to study the pathogenesis of persistent infection and virus-induced oncogenesis.

FUNDED PUBLICATIONS

  • Complete genomic sequence of an Epstein-Barr virus-related herpesvirus naturally infecting a new world primate: a defining point in the evolution of oncogenic lymphocryptoviruses.
  • Reduced prevalence of Epstein-Barr virus-related lymphocryptovirus infection in sera from a new world primate.
  • Summary of roundtable discussion meeting: non-human primates to assess risk for EBV-related lymphomas in humans.
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    22 TRIPLES      17 PREDICATES      23 URIs      9 LITERALS

    Subject Predicate Object
    1 grants:008a0c9b9662d003ff9851f92a2380c8 sg:abstract DESCRIPTION (provided by applicant): Epstein-Barr virus (EBV) is human gamma herpesvirus in the lymphocryptovirus (LCV) genera and is associated with several types of lymphoid and epithelial cell malignancies. Closely related oncogenic LCV are known to naturally infect Old World nonhuman primate species. However, it was believed that LCV did not naturally infect New World primates and were restricted to humans and Old World primates. We have recently isolated a new herpesvirus, CaIHV-3 (Callithrix herpesvirus 3), from spontaneous B cell lymphomas arising in common marmosets (Callithrix jacchus), a New Wofid primate. Like EBV, Ca1HV-3 infection can immortalize B cells in tissue culture and is persistently endemic in the adult population. We have cloned and sequenced more than 125,000 bp of the genome and have definitively identified it as the first member of the EBV-related LCV genera found in New World primates. Significant differences in the repertoire of lytic and latent infection genes in Ca1HV-3 as compared to EBV and other Old World LCV provide new opportunities for studying the molecular pathogenesis and oncogenesis associated with LCV infection. The occurrence of spontaneous lymphomas in immunocompetent animals is a unique and potentially valuable animal model system for studying LCV-induced malignancies. We will utilize the biologic similarities and genetic differences that have evolved among the human, New World, and Old World LCV to better understand EBV infection and pathogenesis in humans. Specific Aim #1. Complete the Ca1HV-3 primary nucleotide sequence. Specific Aim #2. Functional, biochemical, and genetic analyses of the Ca1HV-3 C3 gene, a positional homologue for the three EBNA-3 genes. Specific aim #3. Study the disease association, epidemiology, and evolution of New World LCV. Specific aim #4. Develop an experimental Ca1HV-3 animal model to study the pathogenesis of persistent infection and virus-induced oncogenesis.
    2 sg:endYear 2007
    3 sg:fundingAmount 1378537.0
    4 sg:fundingCurrency USD
    5 sg:hasContribution contributions:4fded1090deec7eeb75a88747430feb5
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    10 sg:hasFundedPublication articles:3be33765acf123a4e4ad51c4d9e5002a
    11 articles:76d8498c6230132ae2998a65ed416f7c
    12 articles:926e1c41ec9361851cb0f6e77e1a24b0
    13 sg:hasFundingOrganization grid-institutes:grid.48336.3a
    14 sg:hasRecipientOrganization grid-institutes:grid.62560.37
    15 sg:language English
    16 sg:license http://scigraph.springernature.com/explorer/license/
    17 sg:scigraphId 008a0c9b9662d003ff9851f92a2380c8
    18 sg:startYear 2001
    19 sg:title New World Oncogenic Lymphocryptoviruses
    20 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=6952411
    21 rdf:type sg:Grant
    22 rdfs:label Grant: New World Oncogenic Lymphocryptoviruses
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