Lack of trans-activation function for Maedi Visna virus and Caprine arthritis encephalitis virus Tat proteins

Abstract

All lentiviruses contain an open reading frame located shortly upstream or inside of the env gene and encoding a small protein which has been designated Tat. This designation was mainly with respect to the positional analogy with the first exon of the trans-activator protein of the well studied human immunodeficiency virus type 1 (HIV-1). In this work we comparatively studied the trans- activation activity induced by Tat proteins of the small ruminant Maedi Visna virus (MVV) of sheep and Caprine arthritis encephalitis virus (CAEV) of goats on MVV and CAEV LTRs with that induced by the human lentivirus HIV-1 on its own LTR. The HIV-1 LTR alone weakly expresses the reporter GFP gene except when the HIV-1 Tat protein is coexpressed, the GFP expression is increased 60-fold. In similar conditions only minimal trans-activation increasing two- to three-fold the MVV and CAEV LTR activity was found with MVV Tat protein, and no trans-activation activity was detected in any used cell type or with any virus strain when CAEV Tat was tested. These results indicate that the small ruminant lentiviruses (SRLV) differ from the primate lentiviruses in their control of expression from the viral LTRs and put into question the biological role of the encoded protein named "Tat."

Equine Infectious Anemia Virus (EIAV): what has HIV?s country cousin got to tell us?

“…A similar mechanism involving cyclin T1 has been described in the context of the EIAV Tat and TAR interaction suggesting that highly divergent Tat and TAR elements control viral gene expression by the same mechanism [1,9,167]. Interestingly, recent studies on the initially named Tat protein of Small Ruminant Lentiviruses (SRLV), infecting goats and sheep, showed that this protein has a minimal effect on the transcriptional level from the LTR [181]. In fact, the gene initially designed as the tat gene may encode a Vpr-like protein, suggesting that SRLV differ from the other lentiviruses in their control of expression from the viral LTR [180].…”

Maedi-Visna Virus and Caprine Arthritis Encephalitis Virus Genomes Encode a Vpr-Like but No Tat Protein

“…It has recently been shown that the proteins translated from the open reading frames identified as tat in the SRLV do not function primarily as up regulators of transcription from the viral LTR, as do the Tat peptides of the primate lentiviruses (29). In the present study we pursued a comparison of the SRLV Tat proteins with the different primate lentivirus accessory and regulatory proteins.…”

“…Some studies have reported an increase in the expression (15) of genes under the control of the MVV or CAEV long terminal repeat (LTR) or a stabilization of the corresponding mRNA (9) in the presence of the corresponding Tat peptide, but the increases in the levels of activity were inconstant and often low, ranging from 1.6-fold (12) to 46-fold (9). We have recently compared the transactivation activities of HIV-1 Tat with Tat proteins from MVV and CAEV on their homologous LTRs in different cell types, including macrophages, from natural host species and found little or no transactivation by SRLV Tat proteins under conditions in which the HIV-1 Tat produced a 60-fold increase in expression of the reporter gene (29). We concluded that transactivation of the homologous LTR was unlikely to be the principal function of the SRLV Tat proteins.…”

Rétrovirus et pathologie comparée

“…La fonction des produits de ces gènes est souvent mal connue. C'est ainsi que le gène tat de CAEV a été nommé en raison de son organisation génique ; en fait le produit de ce gène n'a pas une fonction de type tat comme les lentivirus des primates, c'est-à-dire qu'il n'a pas d'effet sur le niveau de réplication du virus (VILLET et al, 2003a) ; il induit surtout l'arrêt des cellules en phase G2 du cycle cellulaire, fonction classiquement reconnue pour les gènes vpr des lentivirus des primates (VILLET et al, 2003b). De même le rôle de plusieurs des gènes régu-lateurs ou accessoires des lentivirus des primates est mal connu.…”