Maedi-visna virus and caprine arthritis encephalitis virus genomes encode a Vpr-like but no Tat protein.
A small open reading frame (ORF) in maedi-visna virus (MVV) and caprine arthritis encephalitis virus (CAEV) was initially named "tat" by analogy with a similarly placed ORF in the primate lentiviruses. The encoded "Tat" protein was ascribed the function of up regulation of the viral transcription from the long terminal repeat (LTR) promoter, but we have recently reported that MVV and CAEV Tat proteins lack trans-activation function activity under physiological conditions (S. Villet, C. Faure, B. Bouzar, G. Verdien, Y. Chebloune, and C. Legras, Virology 307:317-327, 2003). In the present work, we show that MVV Tat localizes to the nucleus of transfected cells, probably through the action of a nuclear localization signal in its C-terminal portion. We also show that, unlike the human immunodeficiency virus (HIV) Tat protein, MVV Tat was not secreted into the medium by transfected human or caprine cells in the absence of cell lysis but that, like the primate accessory protein Vpr, MVV and CAEV Tat proteins were incorporated into viral particles. In addition, analysis of the primary protein structures showed that small-ruminant lentivirus (SRLV) Tat proteins are more similar to the HIV type 1 (HIV-1) Vpr protein than to HIV-1 Tat. We also demonstrate a functional similarity between the SRLV Tat proteins and the HIV-1 Vpr product in the induction of a specific G(2) arrest of the cell cycle in MVV Tat-transfected cells, which increases the G(2)/G(1) ratio 2.8-fold. Together, these data strongly suggest that the tat ORF in the SRLV genomes does not code for a regulatory transactivator of the LTR but, rather, for a Vpr-like accessory protein.
Villet
Stéphanie
S
UMR 754 INRA/ENVL/UCBL, Rétrovirus et pathologie comparée, "Virologie Cellulaire, Moléculaire, et Maladies Emergentes," Université Claude Bernard Lyon-1, Lyon, France.
Bouzar
Baya Amel
BA
Morin
Thierry
T
Verdier
Gérard
G
Legras
Catherine
C
Chebloune
Yahia
Y
D000818:Animals; D016088:Arthritis-Encephalitis Virus, Caprine / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics; D016195:G2 Phase; D015696:Gene Products, tat / Q000235:genetics / Q000502:physiology; D016336:Gene Products, vpr / Q000235:genetics* / Q000502:physiology; D015756:Genes, tat; D016334:Genes, vpr; D016679:Genome, Viral; D006041:Goats; D006367:HeLa Cells; D006801:Humans; D016366:Open Reading Frames; D013347:Subcellular Fractions / Q000821:virology; D014162:Transfection; D014790:Visna-maedi virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology
D004279:DNA, Viral; D015696:Gene Products, tat; D016336:Gene Products, vpr