Viral fusion peptides induce several signal transduction pathway activations that are essential for interleukin-10 and beta-interferon production.
OBJECTIVE
The deciphering of intracellular signaling pathways that are activated by the interaction between viral fusion peptides and cellular membranes are important for the understanding of both viral replication strategies and host defense mechanisms.


METHODS
Fusion peptides of several enveloped viruses belonging to different virus families were prepared by standard 9-fluorenylmethoxycarbonyl polyamine solid-phase synthesis and used to stimulate U937 cells in vitro to analyze the phosphorylation patterns of the signaling pathways (PKC, Src, Akt, and MAPK pathways). Immunoprecipitation and Western blotting were carried out by using phosphospecific antibodies. All samples were also assayed for the presence of IL-10 and IFN-beta by ELISA and activation of nuclear factors (AP-1 and NF-kappaB).


RESULTS
We have demonstrated that hydrophobic domains of fusion proteins are able to induce several transduction pathways that lead to cytokine (IFN-beta and IL-10) production, an event that appears to be dependent on early activation of AP-1 and NF-kappaB.


CONCLUSIONS
The results obtained on the signaling activity of fusion peptides from different viruses enabled us to shed some light on the complex mechanism of viral entry and more precisely we focused on the exact signaling event induced by hydrophobic domains characteristic of fusion peptides interacting with the cell membrane.
Vitiello
Mariateresa
M
Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy.
Finamore
Emiliana
E
Falanga
Annarita
A
Raieta
Katia
K
Cantisani
Marco
M
Galdiero
Francesco
F
Pedone
Carlo
C
Galdiero
Marilena
M
Galdiero
Stefania
S
D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D016899:Interferon-beta / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D009000:Monocytes / Q000276:immunology; D015398:Signal Transduction; D015533:Transcriptional Activation; D014760:Viral Fusion Proteins / Q000138:chemical synthesis / Q000276:immunology*
D014760:Viral Fusion Proteins; D016753:Interleukin-10; D016899:Interferon-beta