Visna virus, a non-oncogenic retrovirus, is the etiologic agent of a slow demyelinating disease of sheep. The virus causes a lifelong persistent infection in the animal. Infected sheep develop vigorous immune responses which fail to cure the infection. The presence of virus specific DNA in the tissue of infected animals provides a mechanism for viral persistence, but it does not explain the continued expression of infectious virus as well as chronic progressive disease in the presence of neutralizing antibody. Studies in our laboratory have shown that progressive antigenic drift occurs in immune animals. Molecular analysis of these antigenic variants indicate that there is progressive accumulation of point mutations in the viral genome which probably codes for the viral glycoprotein. To understand the molecular events which result in antigenic variation and the molecular basis for viral neutralization we plan to continue our experiments genetically mapping and sequencing the evelope genes of visna virus and the closely related virus CAEV. Using the cloned viral DNAs from visna virus and an antigenic variant LV11 we plan to make recombinants to determine the genetic sites important in antigenic variation. Using the same approach, visna virus and CAEV recombinants will be used to determine what genetic factors determine whether neutralizing antibody is produced to the viral glycoprotein. Finally, monoclonal antibodies are being developed in our lab to investigate the structure of the envelope glycoprotein and to study the genetic sites of antigenic variation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS016145-05
Application #
3396711
Study Section
(SSS)
Project Start
1981-07-01
Project End
1989-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Gdovin, S L; Clements, J E (1992) Molecular mechanisms of visna virus Tat: identification of the targets for transcriptional activation and evidence for a post-transcriptional effect. Virology 188:438-50
Crane, S E; Buzy, J; Clements, J E (1991) Identification of cell membrane proteins that bind visna virus. J Virol 65:6137-43
Crane, S E; Kanda, P; Clements, J E (1991) Identification of the fusion domain in the visna virus transmembrane protein. Virology 185:488-92
Hess, J L; Small, J A; Clements, J E (1989) Sequences in the visna virus long terminal repeat that control transcriptional activity and respond to viral trans-activation: involvement of AP-1 sites in basal activity and trans-activation. J Virol 63:3001-15
Small, J A; Bieberich, C; Ghotbi, Z et al. (1989) The visna virus long terminal repeat directs expression of a reporter gene in activated macrophages, lymphocytes, and the central nervous systems of transgenic mice. J Virol 63:1891-6
Davis, J L; Clements, J E (1989) Characterization of a cDNA clone encoding the visna virus transactivating protein. Proc Natl Acad Sci U S A 86:414-8
Gabuzda, D H; Hess, J L; Small, J A et al. (1989) Regulation of the visna virus long terminal repeat in macrophages involves cellular factors that bind sequences containing AP-1 sites. Mol Cell Biol 9:2728-33
Clements, J E; Gdovin, S L; Montelaro, R C et al. (1988) Antigenic variation in lentiviral diseases. Annu Rev Immunol 6:139-59
Narayan, O; Zink, M C; Huso, D et al. (1988) Lentiviruses of animals are biological models of the human immunodeficiency viruses. Microb Pathog 5:149-57
Pyper, J M; Sheffer, D; Clements, J E et al. (1988) Hyaluronidase enhances cell fusion and synthesis of viral DNA during infection with caprine arthritis encephalitis virus. Microb Pathog 5:399-406

Showing the most recent 10 out of 21 publications