Induction of signaling pathways by herpes simplex virus type 1 through glycoprotein H peptides.
Eukaryotic cells respond to extracellular stimuli, such as viruses, by recruiting signal transduction pathways, many of which are mediated through activation of distinct mitogen-activated protein kinase (MAPK) cascades and activation of transductional regulation factors. The best characterized of this pathway are the extracellular signal regulated kinase (ERK), the c-Jun N-terminal kinase/stress activated protein kinase (JNK/SAPK), and the p38 MAPK cascade. Herpes simplex virus type 1 (HSV-1) encodes at least 11 envelope glycoproteins, which alone or in concert play different roles in viral adsorption, entry, cell-to-cell spread, and immune evasion. Of these proteins, three are designated glycoprotein B (gB), glycoprotein D (gD), and the gH/gL heterodimer, are clearly involved in attachment and entry, and therefore possible candidates in inducing early cellular activation.Nevertheless, the precise role of each glycoprotein and the cellular factor involved remain elusive. The signal transduction pathways involved, and the outcome of cellular activation on viral entry or postentry events, are still to be elucidated. To better understand the role of signal transduction pathways and phosphorylation events in HSV-1 entry, synthetic peptides modeled on HSV-1 gH were synthesized and tested for MEK1-MEK2/MAPK cascade activation. Our results show a major involvement of the JNK pathway in the intracellular signal transmission after stimulation with gH HSV-1 peptides.
Galdiero
Stefania
S
Dipartimento di Chimica Biologica and CIRPEB, Università di Napoli Federico II, Naples, Italy.
Vitiello
Mariateresa
M
D'Isanto
Marina
M
Di Niola
Erminia
E
Peluso
Lucia
L
Raieta
Katia
K
Pedone
Carlo
C
Galdiero
Massimiliano
M
Benedetti
Ettore
E
D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000502:physiology*; D057927:Hydrophobic and Hydrophilic Interactions; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000502:physiology*
D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C044200:glycoprotein H, herpes simplex virus type 1