This study focuses on a virus recently discovered in some isolates of the protozoan parasite Leishmania. This virus was originally detected by the simultaneous presence of a unique RNA polymerase activity and a 6 kilobase RNA species in infected promastigotes. Electron microscopy revealed virus-like particles similar to picornaviruses. Viral preparations were obtained on density gradients and were found to contain the putative double-stranded RNA genome as well as RNA polymerase activity. These observations are consistent with the presence in Leishmania of a dsRNA virus. This virus is reminiscent of those found in yeast and other fungi, as well as viruses demonstrated in two other parasitic protozoan, Giardia and Trichomonas. As viral replication is dependent on the host's molecular pathways, the proposed study focuses not only on the Leishmania virus, but uses this system as a novel approach to study the transcription and translation pathways in kinetoplastid parasites. The main goals of this study are: 1)Characterize on a molecular level the replicative and translational strategy of the Leishmania virus; 2)Identify the virus-encoded proteins; 3)Establish the taxonomic status of the virus and its relationship with viruses from other protozoan and from yeast; 4)Exploit this viral system as an experimental model for studying the unique RNA processing and translation pathways in the Leishmania host.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI029390-04
Application #
3144189
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1991-01-01
Project End
1994-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
Schools of Veterinary Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
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Scheffter, S; Widmer, G; Patterson, J L (1994) Complete sequence of Leishmania RNA virus 1-4 and identification of conserved sequences. Virology 199:479-83
Armstrong, T C; Keenan, M C; Widmer, G et al. (1993) Successful transient introduction of Leishmania RNA virus into a virally infected and an uninfected strain of Leishmania. Proc Natl Acad Sci U S A 90:1736-40
Widmer, G (1993) RNA circularization reveals terminal sequence heterogeneity in a double-stranded RNA virus. Virology 193:11-5
Weeks, R S; Patterson, J L; Stuart, K et al. (1992) Transcribing and replicating particles in a double-stranded RNA virus from Leishmania. Mol Biochem Parasitol 52:207-13
Widmer, G; Patterson, J L (1991) Genomic structure and RNA polymerase activity in Leishmania virus. J Virol 65:4211-5