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J. Biol. Chem., Vol. 277, Issue 22, 19679-19687, May 31, 2002

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Human Herpesvirus 6 Immediate-Early 1 Protein Is a Sumoylated Nuclear Phosphoprotein Colocalizing with Promyelocytic Leukemia Protein-associated Nuclear Bodies^*

Annie Gravel, Jean Gosselin^§¶, and Louis Flamand

From the  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

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 (~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.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY037932.

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