Association of the Caveola Vesicular System with Cellular Entry by Filoviruses

Empig, Cyril; Goldsmith, Mark A.

doi:10.1128/jvi.76.10.5266-5270.2002

Cited by 129 publications

(134 citation statements)

References 44 publications

Supporting

Mentioning

127

Contrasting

Order By: Relevance

“…It has recently been recognized that SV40 enters the host cell through caveolae (10)(11)(12)(13). Ebola virus among other viruses also uses caveolae (29). In the case of SV40, the virions first attach to a receptor related to MHC class I molecules and then translocate to specialized membrane microdomains (lipid rafts), where the virions induce the formation of caveolae and therefore their own internalization (10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

BK Polyoma Virus Allograft Nephropathy: Ultrastructural Features from Viral Cell Entry to Lysis

Drachenberg¹,

Papadimitriou²,

Wali³

et al. 2003

American Journal of Transplantation

View full text Add to dashboard Cite

BK virions must enter the host cell and target their genome to the nucleus in order to complete their life cycle. The mechanisms by which the virions accomplish these tasks are not known. In this morphological study we found that BK virions localized beneath the host cell cytoplasmic membrane in 60-70-nm, smooth (non-coated) monopinocytotic vesicles similar to, or consistent with, caveolae. In the cytoplasm, the monopinocytotic vesicles carrying virions appeared to fuse with a system of smooth, vesicles and tubules that communicated with the rough endoplasmic reticulum and was continuous with the Golgi system. Membrane-bound single virions and large tubuloreticular complexes loaded with virions accumulated in paranuclear locations. Occasional nuclei displayed virions within the perinuclear cisterna in association to the perinuclear viral accumulations. Tubular cells with mature productive infection had large nuclei, distended by daughter virions, whereas they lacked significant numbers of cytoplasmic virions. In addition to virally induced cell necrosis, there was extensive tubular cell damage (apoptosis and necrosis) in morphologically non-infected tubules. The observed ultrastructural interactions between the BK virions and host cells are remarkably similar to viral cell entry and nuclear targeting described for SV40 virus.

show abstract

Section: Discussionmentioning

confidence: 99%

BK Polyoma Virus Allograft Nephropathy: Ultrastructural Features from Viral Cell Entry to Lysis

Drachenberg¹,

Papadimitriou²,

Wali³

et al. 2003

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…Integrin ␣2␤1 differs from other integrin type virus receptors by being the only integrin known to mediate virus entry through caveolae instead of clathrin-coated vesicles (Marjomäki et al, 2002). Caveolae are also involved in the entry of SV40 (Pelkmans et al, 2001;, mouse polyoma virus (Richterova et al, 2001), filoviruses (Empig and Goldsmith, 2002), and some bacteria (Shin et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Clustering Induces a Lateral Redistribution of α2β1 Integrin from Membrane Rafts to Caveolae and Subsequent Protein Kinase C-dependent Internalization

Upla

Marjomäki

Kankaanpää

et al. 2004

MBoC

151

186

View full text Add to dashboard Cite

Integrin ␣2␤1 mediates the binding of several epithelial and mesenchymal cell types to collagen. The composition of the surrounding plasma membrane, especially caveolin-1-and cholesterol-containing membrane structures called caveolae, may be important to integrin signaling. On cell surface ␣2␤1 integrin was located in the raft like membrane domain, rich in GPI-anchored proteins, rather than in caveolae. However, when antibodies were used to generate clusters of ␣2␤1 integrin, they started to move laterally on cell surface along actin filaments. During the lateral movement small clusters fused together. Finally ␣2␤1 integrin was found inside caveolae and subsequently internalized into caveosome-like perinuclear structures. The internalization process, unlike cluster formation or lateral redistribution, was dependent on protein kinase C␣ activity. Caveolae are known to be highly immobile structures and ␣2␤1 integrin clusters represent a previously unknown mechanism to activate endocytic trafficking via caveolae. The process was specific to ␣2␤1 integrin, because the antibody-mediated formation of ␣V integrin clusters activated their internalization in coated vesicles and early endosomes. In addition to natural ligands human echovirus-1 (EV1) gains entry into the cell by binding to ␣2␤1 and taking advantage of ␣2␤1 internalization via caveolae. INTRODUCTIONCaveolae are cave-like invaginations of the cell surface (for reviews see Kurzchalia and Parton, 1999;Parton 2003). They have been described as highly immobile and not involved in constitutive endocytic trafficking (Thomsen et al., 2002). Their internalization can be activated, for example, by the phosphatase inhibitor okadaic acid (Parton et al., 1994). In endothelial cells the interaction of albumin docking protein gp60 and caveolin-1 initiates the endocytosis of caveolae (Minshall et al., 2000). Caveolins are membrane proteins that are molecular markers of caveolae and shown to be crucial for the formation of these structures (Fra et al., 1995). Caveolins can be associated with cell surface growth factor receptors (Couet et al., 1997) and cell adhesion receptors (Wary et al., 1996(Wary et al., , 1998Wei et al., 1999) and caveolae might therefore play a role in cellular signaling. In addition, caveolae have been suggested to participate in the uptake of folate by pinocytosis, but this is still under discussion (Parton, 2003). Caveolin-deficient mice have given novel insight into the function of caveolae. Caveolin-1 gene knockout leads to pulmonary defects, vasoconstriction, or dilatation abnormalities and resistance to diet-induced obesity (Drab et al., 2001;Razani et al., 2001;Schubert et al., 2001;Sotgia et al., 2002;Razani et al., 2002). Simian virus 40 (SV40) has been shown to be internalized through caveolae and detailed studies focused on the virus entry mechanism have produced a lot of new information about the biology of caveolae (Pelkmans et al., 2001. We have recently shown that human echovirus 1 (EV1) is another virus using caveolae in its entry (Mar...

show abstract

“…Dynamin is a GTPase required for the cellular membrane to pinch off endosomes from the plasma membrane and is necessary for clathrin-and caveola-mediated endocytosis and phagocytosis, but it is not required for macropinocytosis (11,12). Caveolae have been shown to provide a vehicle for the entry of many viruses into animal cells (13)(14)(15)(16). For example, simian virus 40 (SV40) utilizes caveolae to be internalized under a neutral conditions (17).…”

mentioning

confidence: 99%

Cell Entry of Avian Reovirus Follows a Caveolin-1-mediated and Dynamin-2-dependent Endocytic Pathway That Requires Activation of p38 Mitogen-activated Protein Kinase (MAPK) and Src Signaling Pathways as Well as Microtubules and Small GTPase Rab5 Protein

Huang

Wang

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Very little is known about the mechanism of cell entry of avian reovirus (ARV). The aim of this study was to explore the mechanism of ARV entry and subsequent infection. Cholesterol mainly affected the early steps of the ARV life cycle, because the presence of cholesterol before and during viral adsorption greatly blocked ARV infectivity. Although we have demonstrated that ARV facilitating p38 MAPK is beneficial for virus replication, its mechanism remains unknown. Here, we show that ARV-induced phosphorylation of caveolin-1 (Tyr 14 ), dynamin-2 expression, and Rac1 activation through activation of p38 MAPK and Src in the early stage of the virus life cycle is beneficial for virus entry and productive infection. The strong inhibition by dynasore, a specific inhibitor of dynamin-2, and depletion of endogenous caveolin-1 or dynamin-2 by siRNAs as well as the caveolin-1 colocalization study implicate caveolin-1-mediated and dynamin-2-dependent endocytosis as a significant avenue of ARV entry. By means of pharmacological inhibitors, dominant negative mutants, and siRNA of various cellular proteins and signaling molecules, phosphorylation of caveolin-1, dynamin-2 expression, and Rac1 activation were suppressed, suggesting that by orchestrating p38 MAPK, Src, and Rac1 signaling cascade in the target cells, ARV creates an appropriate intracellular environment facilitating virus entry and productive infection. Furthermore, disruption of microtubules, Rab5, or endosome acidification all inhibited ARV infection, suggesting that microtubules and small GTPase Rab5, which regulate transport to early endosome, are crucial for survival of ARV and that exposure of the virus to acidic pH is required for productive infection.

show abstract

Association of the Caveola Vesicular System with Cellular Entry by Filoviruses

Cited by 129 publications

References 44 publications

BK Polyoma Virus Allograft Nephropathy: Ultrastructural Features from Viral Cell Entry to Lysis

BK Polyoma Virus Allograft Nephropathy: Ultrastructural Features from Viral Cell Entry to Lysis

Clustering Induces a Lateral Redistribution of α2β1 Integrin from Membrane Rafts to Caveolae and Subsequent Protein Kinase C-dependent Internalization

Cell Entry of Avian Reovirus Follows a Caveolin-1-mediated and Dynamin-2-dependent Endocytic Pathway That Requires Activation of p38 Mitogen-activated Protein Kinase (MAPK) and Src Signaling Pathways as Well as Microtubules and Small GTPase Rab5 Protein

Contact Info

Product

Resources

About