Human Herpesvirus 6 immediate-early 1 protein is a sumoylated nuclear phosphoprotein colocalizing with promyelocytic leukemia protein-associated nuclear bodies.
Immediate-early (IE) proteins are the first proteins expressed following viral entry and play a crucial role in the initiation of infection. We report the cloning and characterization of a full-length IE1 transcript and protein (IE1B) from human herpesvirus 6 (HHV-6) variant B. The IE1B transcript consists of five exons (3720 nucleotides), three of which are coding for the IE1 protein. The 1078-amino acid-long IE1B protein is 62% identical and 75% similar to the 941-amino acid IE1 from HHV-6 variant A. IE1B protein can be detected at 4 h post-infection (P.I.), and it is distributed as small intranuclear structures. The maximal number of IE1 bodies ( approximately 10-12/nucleus) is detected at 12 h P.I. after which the IE1 bodies condense into 1-3 larger entities by 24-48 h P.I. During infection the IE1B protein is phosphorylated on serine and threonine residues. IE1B undergoes further post-translational modification with its conjugation to the small ubiquitin-like modifier (SUMO-1) peptide. IE1B colocalizes with SUMO-1 and promyelocytic leukemia nuclear bodies during infection as well as in transfection experiments. Finally, IE1 from variant B is a weaker transactivator than IE1 from variant A, when assayed using heterologous promoters. Overall, the characterization of the HHV-6 IE1B protein presented highlights the similarity and divergence between IE1 from both variants and provides useful information pertaining to the early phase of infection.
Gravel
Annie
A
Laboratory of Virology, Laboratory of Viral Immunology, Rheumatology and Immunology Research Center, Centre Hospitalier de l'Université Laval Research Center and Faculty of Medicine, Laval University, Sainte-Foy, Quebec G1V 4G2, Canada.
Gosselin
Jean
J
Flamand
Louis
L
D002467:Cell Nucleus / Q000378:metabolism*; D002474:Cell-Free System; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D015654:Herpesvirus 6, Human / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013912:Threonine / Q000737:chemistry; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000071156:Promyelocytic Leukemia Protein; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C458509:immediate-early 1 protein, human herpesvirus 6; C070576:PML protein, human; D013912:Threonine; D012694:Serine; D012313:RNA; D005982:Glutathione Transferase