Sandbox WWC8: Difference between revisions

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''NP-CRM1''

After the viral RNA scripts have been replicated, NP shuttles out of the nucleus by associating with CRM1 (chromosomal maintenance 1), also known as exportin [12]. In this later stage of infection, the concentration of NP in the cytoplasm outweighs the concentration of NP inside the nucleus. It is unknown if this is the case because the nuclear localization signals (NLS) are turned off or because the NLS are overwhelmed by the cytoplasmic accumulation signal (CAS), which describes the interaction between NP and the host cell cytoskeleton [1].

''NP-F-actin''

''NP-F-actin (host cell cytoskeleton)''

During the late stages of the infection, the CAS region on NP acts as a cytoplasmic retention signal by tethering the nucleoprotein to the cytoskeleton. The binding between NP and F-actin was confirmed in vitro and exhibited an affinity of ~1µM with a 1:1 stoicheometry NP:F-actin [12].

''NP-M1''

During packaging and assembly of new viral particles, the M1 protein (matrix protein 1 of influenza A) mediates the encapsidation of RNPs into the viral envelope. This interaction is critical for successful assembly of functional virus progeny and is characterized by direct protein-protein interaction between M1 and NP, which is stabilized by M1 simultaneously binding to the NP-bound RNA [1].

''NP Phosphorylation Profile''

The influenza nucleoprotein in each strain features a fingerprint phosphorylation profile, which undergoes subtle changes during the course of a viral replication cycle. The phosphorylation profile is thought to be responsible for the diverse yet specific NP interactions at different stages in the replication cycle. Only serine residues have been found to be phosphorylated or dephosphorylated in NP. The phosphorylation profile of NP seems to be majorly influenced by the host cell's protein kinase C (PKC). In vitro inhibition of PKC by the phorbol ester 12-O-tetradecanolyphorbol 13-acetate or isoquinoline sulphonamide H7 resulted in significant phosphorylation changes in NP, proving the key role a correct NP phosphorylation profile plays in successful viral replication [5].

==Identification of Antiviral Drug Targets on NP==

Sandbox WWC8: Difference between revisions

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@@ Line 29: / Line 29: @@
 ''NP-CRM1''
+After the viral RNA scripts have been replicated, NP shuttles out of the nucleus by associating with CRM1 (chromosomal maintenance 1), also known as exportin [12]. In this later stage of infection, the concentration of NP in the cytoplasm outweighs the concentration of NP inside the nucleus. It is unknown if this is the case because the nuclear localization signals (NLS) are turned off or because the NLS are overwhelmed by the cytoplasmic accumulation signal (CAS), which describes the interaction between NP and the host cell cytoskeleton [1].
-''NP-F-actin''
+''NP-F-actin (host cell cytoskeleton)''
+During the late stages of the infection, the CAS region on NP acts as a cytoplasmic retention signal by tethering the nucleoprotein to the cytoskeleton. The binding between NP and F-actin was confirmed in vitro and exhibited an affinity of ~1µM with a 1:1 stoicheometry NP:F-actin [12].
 ''NP-M1''
+During packaging and assembly of new viral particles, the M1 protein (matrix protein 1 of influenza A) mediates the encapsidation of RNPs into the viral envelope. This interaction is critical for successful assembly of functional virus progeny and is characterized by direct protein-protein interaction between M1 and NP, which is stabilized by M1 simultaneously binding to the NP-bound RNA [1].
 ''NP Phosphorylation Profile''
+The influenza nucleoprotein in each strain features a fingerprint phosphorylation profile, which undergoes subtle changes during the course of a viral replication cycle. The phosphorylation profile is thought to be responsible for the diverse yet specific NP interactions at different stages in the replication cycle. Only serine residues have been found to be phosphorylated or dephosphorylated in NP. The phosphorylation profile of NP seems to be majorly influenced by the host cell's protein kinase C (PKC). In vitro inhibition of PKC by the phorbol ester 12-O-tetradecanolyphorbol 13-acetate or isoquinoline sulphonamide H7 resulted in significant phosphorylation changes in NP, proving the key role a correct NP phosphorylation profile plays in successful viral replication [5].
 ==Identification of Antiviral Drug Targets on NP==