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Characterization of a new 5' splice site within the caprine arthritis encephalitis virus genome: evidence for a novel auxiliary protein.
- Source :
-
Retrovirology [Retrovirology] 2008 Feb 29; Vol. 5, pp. 22. Date of Electronic Publication: 2008 Feb 29. - Publication Year :
- 2008
-
Abstract
- Background: Lentiviral genomes encode multiple structural and regulatory proteins. Expression of the full complement of viral proteins is accomplished in part by alternative splicing of the genomic RNA. Caprine arthritis encephalitis virus (CAEV) and maedi-visna virus (MVV) are two highly related small-ruminant lentiviruses (SRLVs) that infect goats and sheep. Their genome seems to be less complex than those of primate lentiviruses since SRLVs encode only three auxiliary proteins, namely, Tat, Rev, and Vif, in addition to the products of gag, pol, and env genes common to all retroviruses. Here, we investigated the central part of the SRLV genome to identify new splice elements and their relevance in viral mRNA and protein expression.<br />Results: We demonstrated the existence of a new 5' splice (SD) site located within the central part of CAEV genome, 17 nucleotides downstream from the SD site used for the rev mRNA synthesis, and perfectly conserved among SRLV strains. This new SD site was found to be functional in both transfected and infected cells, leading to the production of a transcript containing an open reading frame generated by the splice junction with the 3' splice site used for the rev mRNA synthesis. This open reading frame encodes two major protein isoforms of 18- and 17-kDa, named Rtm, in which the N-terminal domain shared by the Env precursor and Rev proteins is fused to the entire cytoplasmic tail of the transmembrane glycoprotein. Immunoprecipitations using monospecific antibodies provided evidence for the expression of the Rtm isoforms in infected cells. The Rtm protein interacts specifically with the cytoplasmic domain of the transmembrane glycoprotein in vitro, and its expression impairs the fusion activity of the Env protein.<br />Conclusion: The characterization of a novel CAEV protein, named Rtm, which is produced by an additional multiply-spliced mRNA, indicated that the splicing pattern of CAEV genome is more complex than previously reported, generating greater protein diversity. The high conservation of the SD site used for the rtm mRNA synthesis among CAEV and MVV strains strongly suggests that the Rtm protein plays a role in SRLV propagation in vivo, likely by competing with Env protein functions.
- Subjects :
- Amino Acid Sequence
Animals
Arthritis-Encephalitis Virus, Caprine genetics
Base Sequence
Cells, Cultured
Cloning, Molecular
Goats
Humans
Membrane Glycoproteins metabolism
Molecular Sequence Data
Molecular Weight
Open Reading Frames genetics
Protein Isoforms chemistry
Protein Isoforms genetics
Protein Isoforms metabolism
RNA Splice Sites genetics
Viral Envelope Proteins physiology
Viral Proteins chemistry
Viral Proteins metabolism
Arthritis-Encephalitis Virus, Caprine physiology
Genome, Viral
Viral Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1742-4690
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Retrovirology
- Publication Type :
- Academic Journal
- Accession number :
- 18312636
- Full Text :
- https://doi.org/10.1186/1742-4690-5-22