Host cell-virus cross talk: phosphorylation of a hepatitis B virus envelope protein mediates intracellular signaling.
Phosphorylation of cytosolic pre-S domains of the duck hepatitis B virus (DHBV) large envelope protein (L) was identified as a regulatory modification involved in intracellular signaling. By using biochemical and mass spectrometric analyses of phosphopeptides obtained from metabolically radiolabeled L protein, a single phosphorylation site was identified at serine 118 as part of a PX(S/T)P motif, which is strongly preferred by ERK-type mitogen-activated protein kinases (MAP kinases). ERK2 specifically phosphorylated L at serine 118 in vitro, and L phosphorylation was inhibited by a coexpressed MAP kinase-specific phosphatase. Furthermore, L phosphorylation and ERK activation were shown to be induced in parallel by various stimuli. Functional analysis with transfected cells showed that DHBV L possesses the ability to activate gene expression in trans and, by using mutations eliminating (S-->A) or mimicking (S-->D) serine phosphorylation, that this function correlates with L phosphorylation. These mutations had, however, no major effects on virus production in cell culture and in vivo, indicating that L phosphorylation and transactivation are not essential for hepadnavirus replication and morphogenesis. Together, these data suggest a role of the L protein in intracellular host-virus cross talk by varying the levels of pre-S phosphorylation in response to the state of the cell.
Rothmann
K
K
Zentrum für Molekulare Biologie Heidelberg, D-69124 Heidelberg, Germany.
Schnölzer
M
M
Radziwill
G
G
Hildt
E
E
Moelling
K
K
Schaller
H
H
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D004372:Ducks; D015967:Gene Expression Regulation, Viral; D015611:Hepatitis B Virus, Duck / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D015398:Signal Transduction; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
C077433:Pre-S protein, Duck hepatitis B virus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1