Epidermal growth factor receptor occupancy inhibits vaccinia virus infection

Eppstein, Deborah A.; Marsh, Y V; Schreiber, Alain B.; Newman, Sherry R.; Todaro, George J.; Nestor, John J.

doi:10.1038/318663a0

Cited by 124 publications

(42 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Eppstein et al (1985) obtained results that suggested that EGF receptors might also serve as the cellular receptors for vaccinia virus, which would bind to these via a precursor of its growth factor incorporated into its enclosing membrane. This idea is, however, difficult to reconcile with the finding of Stroobant et al (1985) that vaccinia virus can infect NR-6 cells, which lack EGF receptors.…”

Section: The Ribosomal Protein $6 Kinasementioning

confidence: 87%

Viral Aspects of Protein Phosphorylation

Leader

Katan

1988

Journal of General Virology

View full text Add to dashboard Cite

Section: The Ribosomal Protein $6 Kinasementioning

confidence: 87%

Viral Aspects of Protein Phosphorylation

Leader

Katan

1988

Journal of General Virology

View full text Add to dashboard Cite

“…Blocking this receptor with antibodies and other agents has previously been shown to inhibit VACV infection in L cells (29,30). However, its role as a VACV receptor has been largely dismissed because the virus infects cells, such as CHO cells, devoid of EGFR (31).…”

Section: Discussionmentioning

confidence: 99%

Vaccinia virus strains use distinct forms of macropinocytosis for host-cell entry

Mercer

Knébel

Schmidt

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

147

159

View full text Add to dashboard Cite

To enter host cells, vaccinia virus, a prototype poxvirus, can induce transient macropinocytosis followed by endocytic internalization and penetration through the limiting membrane of pinosomes by membrane fusion. Although mature virions (MVs) of the Western reserve (WR) strain do this in HeLa cells by activating transient plasma membrane blebbing, MVs from the International Health Department-J strain were found to induce rapid formation (and lengthening) of filopodia. When the signaling pathways underlying these responses were compared, differences were observed at the level of Rho GTPases. Key to the filopodial formation was the virus-induced activation of Cdc42, and for the blebbing response the activation of Rac1. In addition, unlike WR, International Health Department-J MVs did not rely on genistein-sensitive tyrosine kinase and PI(3)K activities. Only WR MVs had membrane fusion activity at low pH. Inhibitor profiling showed that MVs from both strains entered cells by macropinocytosis and that this was induced by virion-exposed phosphatidylserine. Both MVs relied on the activation of epidermal growth factor receptor, on serine/ threonine kinases, protein kinase C, and p21-activated kinase 1. The results showed that different strains of the same virus can elicit dramatically different responses in host cells during entry, and that different macropinocytic mechanisms are possible in the same cell line through subtle differences in the activating ligand.epidermal growth factor receptor | endocytosis | poxvirus | Rho GTPases | virus entry

show abstract

“…7). The important contribution of the EGF receptor to viral entry and for propagation of VV infection has been previously reported (23); however, several studies indicated that this receptor is not an essential determinant in the infection pathway (15,41). Figure 7 depicts the net fluorescence emission induced by VV interactions (at a low MOI of 1 PFU per cell) in PDAlabeled CHO cells without receptor saturation by the EGF hormone and following receptor saturation (2 g/ml EGF hormone) (32).…”

Section: Resultsmentioning

confidence: 99%

Vaccinia Virus Interactions with the Cell Membrane Studied by New Chromatic Vesicle and Cell Sensor Assays

Orynbayeva¹,

Kolusheva²,

Groysman³

et al. 2007

J Virol

View full text Add to dashboard Cite

The potential danger of cross-species viral infection points to the significance of understanding the contributions of nonspecific membrane interactions with the viral envelope compared to receptor-mediated uptake as a factor in virus internalization and infection. We present a detailed investigation of the interactions of vaccinia virus particles with lipid bilayers and with epithelial cell membranes using newly developed chromatic biomimetic membrane assays. This analytical platform comprises vesicular particles containing lipids interspersed within reporter polymer units that emit intense fluorescence following viral interactions with the lipid domains. The chromatic vesicles were employed as membrane models in cell-free solutions and were also incorporated into the membranes of epithelial cells, thereby functioning as localized membrane sensors on the cell surface. These experiments provide important insight into membrane interactions with and fusion of virions and the kinetic profiles of these processes. In particular, the data emphasize the significance of cholesterol/sphingomyelin domains (lipid rafts) as a crucial factor promoting bilayer insertion of the viral particles. Our analysis of virus interactions with polymer-labeled living cells exposed the significant role of the epidermal growth factor receptor in vaccinia virus infectivity; however, the data also demonstrated the existence of additional non-receptor-mediated mechanisms contributing to attachment of the virus to the cell surface and its internalization.The essential initial step in the viral infection process involves transport of the virus or its genetic components through the host cell membrane. Membrane interactions and penetration of viral particles are generally complex multistep processes determined by varied factors and molecular events that have been elucidated for only a few viral species. Indeed, revealing the mechanisms of membrane binding by viral particles, bilayer fusion with the viral coat, and eventual virus internalization into the host cell is critical for understanding viral infection and propagation. In particular, determining the contributions of virus-lipid interactions to cell entry (rather than receptormediated uptake) is essential for gaining insight into the factors affecting cross-species infectivity.Vaccinia virus (VV) is a member of the Poxviridae family, which coinfect a wide variety of mammalian cells. The two infectious forms of vaccinia virions include the intracellular mature virus (IMV) and the extracellular enveloped virus (EEV), which are structurally distinct and exhibit different biological features (1). The IMV is a single-enveloped particle containing different viral proteins on its membrane (18) and represents the majority of infectious progeny produced in cells and responsible for virus proliferation among neighboring cells. EEV has an additional outer membrane with specific proteins and corresponds to infecting distant cells (39). The precise mechanisms of VV entry into host cells have not been ful...

show abstract

Epidermal growth factor receptor occupancy inhibits vaccinia virus infection

Cited by 124 publications

References 12 publications

Viral Aspects of Protein Phosphorylation

Viral Aspects of Protein Phosphorylation

Vaccinia virus strains use distinct forms of macropinocytosis for host-cell entry

Vaccinia Virus Interactions with the Cell Membrane Studied by New Chromatic Vesicle and Cell Sensor Assays

Contact Info

Product

Resources

About