Dataset Information

Transport of influenza virus neuraminidase (NA) to host cell surface is regulated by ARHGAP21 and Cdc42 proteins.

ABSTRACT: Influenza virus neuraminidase (NA) is transported to the virus assembly site at the plasma membrane and is a major viral envelope component that plays a critical role in the release of progeny virions and in determination of host range restriction. However, little is known about the host factors that are involved in regulating the intracellular and cell surface transport of NA. Here we identified the Cdc42-specific GAP, ARHGAP21 differentially expressed in host cells infected with influenza A virus using cDNA microarray analysis. Furthermore, we have investigated the involvement of Rho family GTPases in NA transport to the cell surface. We found that expression of constitutively active or inactive mutants of RhoA or Rac1 did not significantly affect the amount of NA that reached the cell surface. However, expression of constitutively active Cdc42 or depletion of ARHGAP21 promoted the transport of NA to the plasma membranes. By contrast, cells expressing shRNA targeting Cdc42 or overexpressing ARHGAP21 exhibited a significant decrease in the amount of cell surface-localized NA. Importantly, silencing Cdc42 reduced influenza A virus replication, whereas silencing ARHGAP21 increased the virus replication. Together, our results reveal that ARHGAP21- and Cdc42-based signaling regulates the NA transport and thereby impacts virus replication.

SUBMITTER: Wang S

PROVIDER: S-EPMC3323004 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transport of influenza virus neuraminidase (NA) to host cell surface is regulated by ARHGAP21 and Cdc42 proteins.

Wang Song S Li Hua H Chen Yuhai Y Wei Haitao H Gao George F GF Liu Hongqiang H Huang Shile S Chen Ji-Long JL

The Journal of biological chemistry 20120208 13

Influenza virus neuraminidase (NA) is transported to the virus assembly site at the plasma membrane and is a major viral envelope component that plays a critical role in the release of progeny virions and in determination of host range restriction. However, little is known about the host factors that are involved in regulating the intracellular and cell surface transport of NA. Here we identified the Cdc42-specific GAP, ARHGAP21 differentially expressed in host cells infected with influenza A vi ...[more]

PMID: 22318733

Similar Datasets

Project description:BackgroundInfluenza A virus (IAV) neuraminidase (NA) cleaves sialic acids (Sias) from glycans. Inhibiting NA with oseltamivir suppresses both viral infection, and viral release from cultured human airway epithelial cells. The role of NA in viral exit is well established: it releases budding virions by cleaving Sias from glycoconjugates on infected cells and progeny virions. The role of NA in viral entry remains unclear. Host respiratory epithelia secrete a mucus layer rich in heavily sialylated glycoproteins; these could inhibit viral entry by mimicking sialylated receptors on the cell surface. It has been suggested that NA allows influenza to penetrate the mucus by cleaving these sialylated decoys, but the exact mechanism is not yet established.MethodsWe tested IAV interaction with secreted mucus using frozen human trachea/bronchus tissue sections, and bead-bound purified human salivary mucins (HSM) and purified porcine submaxillary mucins (PSM). The protective effect of mucus was analyzed using MDCK cells coated with purified HSM and PSM with known Sia content. Oseltamivir was used to inhibit NA activity, and the fluorescent reporter substrate, 4MU-Neu5Ac, was used to quantify NA activity.ResultsIAV binds to the secreted mucus layer of frozen human trachea/bronchus tissues in a Sia dependent manner. HSM inhibition of IAV infection is Sia dose-dependent, but PSM cannot inhibit infection of underlying cells. HSM competitively inhibits NA cleavage of 4MU-Neu5Ac, reporter substrate. Human IAV effectively cleaves Sias from HSM but not from PSM, and binds to HSM but not to PSM.ConclusionIAV interacts with human mucus on frozen tissue sections and mucus-coated beads. Inhibition of IAV infection by sialylated human mucus is dose-dependent, and enhanced when NA is inhibited with oseltamivir. Thus NA cleaves sialylated decoys during initial stages of infection. Understanding IAV interactions with host mucins is a promising new avenue for drug development.

Dataset Information

Transport of influenza virus neuraminidase (NA) to host cell surface is regulated by ARHGAP21 and Cdc42 proteins.

Publications

Transport of influenza virus neuraminidase (NA) to host cell surface is regulated by ARHGAP21 and Cdc42 proteins.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets