April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
A Phagocytosis-Like Mechanism May Facilitate Herpesvirus Induced Cell Fusion
Author Affiliations & Notes
  • D. Shukla
    Ophthalmology/Visual Sciences, Univ of Illinois at Chicago, Chicago, Illinois
  • C. D. O'Donnell
    Ophthalmology/Visual Sciences, Univ of Illinois at Chicago, Chicago, Illinois
  • Footnotes
    Commercial Relationships  D. Shukla, None; C.D. O'Donnell, None.
  • Footnotes
    Support  NIH grant AI057860 and unrestricted funds from RPB
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 842. doi:
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      D. Shukla, C. D. O'Donnell; A Phagocytosis-Like Mechanism May Facilitate Herpesvirus Induced Cell Fusion. Invest. Ophthalmol. Vis. Sci. 2009;50(13):842.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Herpesviruses cause myriads of eye problems including fusion of infected cells with uninfected cells or cyncytia formation to facilitate viral spread. The goal of the present study was to perform ultrastructural and real-time analyses of Herpes Simplex Virus type 1 (HSV-1) induced cell-to-cell fusion and to determine the significance of receptors and cellular signaling mediators in the cell-to-cell fusion process.

Methods: : High resolution laser confocal microscopy and fluorescent microscopy were used to monitor fusion of viral glycoprotein (gB, gD, gH and gL)-expressing cells with other susceptible cells. A recombinant GFP-expressing HSV-1(K26GFP) was also used to monitor virus-induced cell-to-cell fusion. Immunoprecipitation and Western blot analyses were performed for the determination of signaling events. Inhibitors of actin polymerization and dominant negative Rho GTPase mutants were used to probe the significance of phagocytosis in the fusion process.

Results: : Expression of four HSV-1 glycoproteins (gB, gD, gH and gL) generate the ability in cells to rapidly fuse with cells expressing viral receptors HVEM, nectin-1 and 3-O sulfated heparan sulfate. The glycoprotein expressing cells demonstrate higher mobility and in most cases, make the first contact with receptor-expressing cells. As giant cells form after initial fusion events, a phagocytosis-like process becomes more visible by live-cell imaging. Filopodia are used for bringing cells in close proximity. CDC41 and RhoA are activated during fusion and dominant negative mutants of both can inhibit the process. Role of heparan sulfate (HS) is that of a negative regulator. Cells that lack HS tend to fuse more and form larger size cyncytia. Both CDC41 and RhoA are recruited to fusion sites and in many cases, phagosomes containing glycoprotein-expressing cells can be observed.

Conclusions: : A phagocytosis-like mechanism may be involved in the fusion of viral glycoprotein-expressing cells with that of the receptor-expressing cells. Rho GTPases play an important role in the fusion process and HS negatively regulate it.

Keywords: herpes simplex virus • glycoconjugates/glycoproteins • imaging/image analysis: non-clinical 

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