T-CELL LYMPHOTROPIC VIRUSES OF MACAQUES

Project: Research project

Description

The recently discovered human T-cell leukemia virus (HTLV) types I and II
are associated with forms of human leukemia and lymphoma. Lymphomas have
been the most frequently observed neoplasm in the NERPRC macaque cololy and
eight of ten NERPRC macques with lymphomas or lymphoproliferative disorders
had antibodies reactive with HTLV. T-cell lymphotropic viruses of macaques
(MaTLV) will be isolated. The isolates will be characterized in terms of
ultrastructural features, reverse transcriptase activity and cell tropism.
The in vitro host range of MaTLV isolates will be determined with
particular emphasis on its ability to infect and transform a variety of
human and monkey cells. Verification that isolates are related to HTLV
will be obtained by reactivity of antigenic proteins in infected cells with
defined sera and by hybridization of DNA from infected cells with cloned
HTLV DNA. The major proteins of MaTLV will be identified by polyacrylamide gel
electrophoresis of purified virions. Viral proteins will be further
characterized in terms of their glycosylation, the role of cellular
processing in their production and their relatedness to the major proteins
of HTLVI and II. Major antigens will be genetically mapped by radiolabel
sequencing techniques. The relatedness of MaTLV to HTLVI and II will be determined by Southern
blot hybridization of DNA from infected cells. Cloned MaTLV DNA will be
prepared and used for restriction endonuclease mapping, for analysis of
various isolates and for detection of viral genomes in lymphoma DNAs.
Cloned MaTLV DNA will also be used for detailed comparisons with HTLVI and
II by restriction site alignments and degree of homology along the genome. To investigate the role of MaTLV in macaque disease, seroepidemiologic
studies will be conducted to determine age of exposure, modes of
transmission and sex predisposition to infection. A search for viral
genetic information in lymphomas will be performed. Attempts will be made
to induce disease in naive macaques. Studies to date have indicated numerous parallels between the human and
macaque systems; characterization of this virus and its biology in the
macaque host will contribute significantly to our knowledge of the HTLV
family. If lymphomas or other disease can be induced in macaques by
experimental infection with MaTLV, various approaches to vaccination and
therapeutic intervention can be studied in a meaningful manner.
StatusFinished
Effective start/end date8/1/857/31/88

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Macaca
Lymphoma
Viruses
T-Lymphocytes
DNA
Deltaretrovirus
Restriction Mapping
Human T-lymphotropic virus 1
Tropism
Viral Genome
Host Specificity
RNA-Directed DNA Polymerase
Viral Proteins
Infection
Glycosylation
Virion
Haplorhini
Leukemia
Vaccination
Proteins

ASJC

  • Medicine(all)