An N-terminal arginine-rich cluster and a proline-alanine-threonine repeat region determine the cellular localization of the herpes simplex virus type 1 ICP34.5 protein and its ligand, protein phosphatase 1.
The ICP34.5 protein facilitates herpes simplex virus replication by binding and activating protein phosphatase 1 (PP1) by means of a very conserved C-terminal GADD34-like region. Natural variants of the ICP34.5 differing in the number of arginines in an Arg-rich cluster at the N terminus and the number of Pro-Ala-Thr repeats in the central bridge region of the protein were cloned as fusion proteins with a reporter peptide (c-Myc or hrGFP) at the C terminus. The natural variants were obtained from strains differing in passage history, tissue culture behavior, and neuroinvasive disease potential. In transfected cells, these variants localized to different subcellular compartments. The N-terminal Arg-rich cluster acted as a cellular localization signal for discrete regions of the nucleus and cytoplasm, but the ultimate location of ICP34.5 was determined by the number of Pro-Ala-Thr repeats in the central bridge region. PP1 colocalized with the ICP34.5 variant in cells expressing the ICP34.5. The ICP34.5-mediated, herpes simplex virus strain-dependent differences in the modulation of PP1 location and function may be responsible for the strain-associated differences in tissue culture behavior and virulence of the virus.
Mao
Hanwen
H
Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA.
Rosenthal
Kenneth S
KS
D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001483:Base Sequence; D002451:Cell Compartmentation; D002522:Chlorocebus aethiops; D017931:DNA Primers; D019084:Fluorescent Antibody Technique, Indirect; D008024:Ligands; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D054645:Protein Phosphatase 1; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
D017931:DNA Primers; D008024:Ligands; D011994:Recombinant Proteins; D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1; D013912:Threonine; D001120:Arginine; D011392:Proline; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D000409:Alanine