Host-cell-dependent role of actin cytoskeleton during the replication of a human strain of influenza A virus

Arcangeletti, Maria Cristina; Ferraglia, F.; Pinardi, Federica; Gatti, Rita; Orlandini, Guido; Covan, Silvia; Motta, Federica; Rodighiero, Isabella; Dettori, G.; Chezzi, Carlo

doi:10.1007/s00705-008-0103-0

Cited by 21 publications

(18 citation statements)

References 65 publications

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“…We previously demonstrated a host-dependent role of the actin cytoskeleton in inducing restriction during the early phases of human influenza A/NWS/33 virus infection in mammalian kidney cells [25]. Moreover, we showed the differential infectious entry of NWS virus in mammalian kidney cells [26].…”

Section: Introductionmentioning

confidence: 72%

Highly Dynamic Microtubules Improve the Effectiveness of Early Stages of Human Influenza A/NWS/33 Virus Infection in LLC-MK2 Cells

et al. 2012

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BackgroundThis study aims to investigate the role of microtubule dynamics in the initiation of NWS/33 human influenza A (NWS) virus infection in MDCK and LLC-MK2 mammalian kidney cells. We previously demonstrated a host-dependent role of the actin cytoskeleton in inducing restriction during the early phases of NWS infection. Furthermore, we showed the differential infectious entry of NWS virus in the above mentioned cell models.Methodology/Principal FindingsBy first employing a panel of microtubule-modulators, we evidenced that microtubule-stabilization negatively interferes with NWS replication in LLC-MK2 but not in MDCK cells. Conversely, microtubule-depolymerization improves NWS growth in LLC-MK2 but not in the MDCK model. By using immunofluorescence labelling and Western blotting analyses upon NWS infection in mammalian kidney cells, it was observed that the occurrence of alpha-tubulin hyperacetylation - a post-translational modified form suggestive of stable microtubules - was significantly delayed in LLC-MK2 when compared to MDCK cells. Furthermore, mock-infected LLC-MK2 cells were shown to have higher levels of both acetylated alpha-tubulin and microtubule-associated protein 4 (MAP4), the latter being essential for the maintenance of normal microtubule polymer levels in interphase epithelial cells. Finally, to obtain highly dynamic microtubules in LLC-MK2 cells, we knocked down the expression of MAP4 by using a RNA-mediated RNA interference approach. The results evidenced that MAP4 silencing improves NWS growth in LLC-MK2 cells.ConclusionBy evidencing the cell type-dependent regulatory role of microtubule dynamics on NWS replication in mammalian kidney cells, we demonstrated that microtubule-stabilization represents a restriction factor for the initiation of NWS infection in LLC-MK2 but not in MDCK cells.

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Section: Introductionmentioning

confidence: 72%

Highly Dynamic Microtubules Improve the Effectiveness of Early Stages of Human Influenza A/NWS/33 Virus Infection in LLC-MK2 Cells

et al. 2012

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“…In vitro experiments studying influenza infection in epithelial cell lines in the presence of cytD revealed that virus entry is differentially affected in polarized and nonpolarized epithelial cells (Arcangeletti et al, 2008;Sun and Whittaker, 2007). In nonpolarized cells, virus entry was not affected when cells were treated with cytD, whereas virus entry into polarized cells required an intact actin system.…”

Section: Discussionmentioning

confidence: 97%

Virosomes can enter cells by non-phagocytic mechanisms

Hofer

Lehmann

Waelti

et al. 2009

Journal of Liposome Research

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Phagocytosis of fine particles (1 microm) by macrophages is a ligand-receptor-mediated, actin-based process, whereas the entering of smaller particles (< or = 0.2 microm) in macrophages occurs also by other mechanisms. Virosomes with a diameter of 0.12-0.18 microm are widely used as carrier systems for drugs, vectors, and plasmids in cancer therapy or for vaccines. We investigated their interactions with airway cells, in particular penetration into monocyte-derived macrophages. The microscopic analysis of phagocytic cells incubated with virosomes and polystyrene particles showed that virosomes and particles penetrated cells even in the presence of cytochalasin D, a drug inhibiting actin-based phagocytosis. The charge of the virosomes and particles did not influence their penetration. Also, different inhibitors of endocytotic pathways did not prevent the particles and virosomes from penetrating into the cells. Additionally, to study the ability of virosomes to overcome the epithelial airway barrier, a triple cell co-culture model composed of epithelial cells, monocyte-derived macrophages and dendritic cells of the respiratory tract was used. We found virosomes and polystyrene particles in both populations of antigen-presenting cells, monocyte-derived macrophages, and dendritic cells, in the latter even if they were not directly exposed. In conclusion, virosomes are readily taken up by monocyte-derived macrophages, both by conventional phagocytosis and by actin-independent mechanisms. Further, they can penetrate the airway barrier and reach resident dendritic cells. Therefore, virosomes are promising vaccine candidates.

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“…Mosquito actin bound both structural and nonstructural proteins from West Nile and dengue viruses. Actin has been indicated in various roles in the life cycles of several viruses, including replication of influenza A (Arcangeletti et al, 2008), the assembly of HIV-1 (Jolly, Mitar, and Sattentau, 2007) and the release of vaccinia (Arakawa et al, 2007). The inhibition of actin polymerization in mosquito cells using latrunculin-A and cytochalasin D lowered the infection of the cells with both dengue and West Nile virus, though it had a greater impact on West Nile infection.…”

Section: Discussionmentioning

confidence: 99%

Use of a tandem affinity purification assay to detect interactions between West Nile and dengue viral proteins and proteins of the mosquito vector

et al. 2011

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West Nile and dengue viruses are (re)emerging mosquito-borne flaviviruses that cause significant morbidity and mortality in man. The identification of mosquito proteins that associate with flaviviruses may provide novel targets to inhibit infection of the vector or block transmission to humans. Here, a tandem affinity purification (TAP) assay was used to identify 18 mosquito proteins that interact with dengue and West Nile capsid, envelope, NS2A or NS2B proteins. We further analyzed the interaction of mosquito cadherin with dengue and West Nile virus envelope protein using co-immunoprecipitation and immunofluorescence. Blocking the function of select mosquito factors, including actin, myosin, PI3-kinase and myosin light chain kinase, reduced both dengue and West Nile virus infection in mosquito cells. We show that the TAP method may be used in insect cells to accurately identify flaviviral-host protein interactions. Our data also provides several targets for interrupting flavivirus infection in mosquito vectors.

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Host-cell-dependent role of actin cytoskeleton during the replication of a human strain of influenza A virus

Cited by 21 publications

References 65 publications

Highly Dynamic Microtubules Improve the Effectiveness of Early Stages of Human Influenza A/NWS/33 Virus Infection in LLC-MK2 Cells

Highly Dynamic Microtubules Improve the Effectiveness of Early Stages of Human Influenza A/NWS/33 Virus Infection in LLC-MK2 Cells

Virosomes can enter cells by non-phagocytic mechanisms

Use of a tandem affinity purification assay to detect interactions between West Nile and dengue viral proteins and proteins of the mosquito vector

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