Disease relevance of tat

• Once targeted to the visna virus promoter, the Tat protein could then interact with basal transcription factors to activate transcription [1].
• Using an infectious molecular clone of CAEV the role of the tat ORF in viral replication was examined [2].
• Conserved sequence motifs involving the tat reading frame of Brazilian caprine lentiviruses indicate affiliations to both caprine arthritis-encephalitis virus and visna-maedi virus [3].
• The sequence variation in small ruminant lentiviruses from Brazilian herds of milking goats was sampled in a representative region of the pol gene and in a region including the entire tat open reading frame [3].
• Finally, tat peptide toxicity was also reduced by blockade of L-type calcium channels [4].

High impact information on tat

• Targeting of the visna virus tat protein to AP-1 sites: interactions with the bZIP domains of fos and jun in vitro and in vivo [1].
• The Tat protein regulates transcription through an AP-1 site proximal to the TATA box within the viral long terminal repeat (LTR) [5].
• These studies strongly suggest that this leucine-rich domain is responsible for targeting the Tat protein to AP-1 sites in the viral LTR [5].
• Moreover, we were able to isolate tat mutant CAEV from blood-derived macrophages that was still able to infect synovial membrane cells in vitro [6].
• Three different tat gene mutants of an infectious molecular clone of CAEV were used to study their replication after transfection or infection of primary goat synovial membrane cells and of blood-derived mononuclear cells or macrophages [6].

Chemical compound and disease context of tat

• The overlap between the vif and tat open reading frames clearly distinguished between CAEV-like small ruminant lentiviruses, which shared eight common nucleotides, and the VMV group, where the overlap was reduced to a single base; the final adenine of the vif terminator (TAA) is the initial adenine of the presumptive tat initiator codon [3].

Biological context of tat

• The visna virus Tat protein is required for efficient viral transcription from the visna virus long terminal repeat (LTR) [1].
• These data demonstrated that the greatest overall conservation of nucleotide sequences occurred in the gag and pol gene regions and two smaller regions, sor and the putative tat gene [7].
• Sequence analysis of the CAEV genome revealed the presence of a small open reading frame (ORF) which shares amino acid identity with the visna virus tat gene [2].
• To test for tat mediated trans-activation a plasmid expressing the CAEV tat ORF was co-transfected with plasmids containing either the CAEV or visna virus LTR driving transcription of the bacterial chloramphenicol acetyltransferase gene (CAT) [2].
• Our results showed no difference between replication of the wild type and either the complete tat deletion mutant or the tat stop point mutant, whereas slower growth kinetics and lower levels of expression of the partial tat deletion mutant that of the wild type were obtained in these cells [6].

Associations of tat with chemical compounds

• We have investigated the neurotoxic mechanisms of a synthetic peptide of transactivating protein tat of MVV in striatal neuronal cultures [4].
• These results indicate that cellular calcium entry through voltage-gated calcium channels following activation of both NMDA and non-NMDA receptors, and subsequent accumulation of intracellular calcium may contribute to the neuronal death induced by tat protein [4].

Other interactions of tat

• Analysis of the gag and rev proteins in the transfected cells demonstrated that these proteins were not detectable in cells transfected with the tat mutants but could be readily detected when the mutations were complemented in trans with a tat expression vector [2].

References