Early herpes simplex virus type 1 infection is dependent on regulated Rac1/Cdc42 signalling in epithelial MDCKII cells.
The aim of this study was to understand how molecular determinants of epithelial cells influence initial infection by herpes simplex virus type 1 (HSV-1). Upon infection of the epithelial MDCKII cell line, enhanced association of virus particles with cells forming actin protrusions was observed, suggesting a putative role of actin dynamics in HSV-1 infection. Thus, the impact of the small Rho-like GTPases Rac1, Cdc42 and RhoA acting as key regulators of actin dynamics was addressed. Endogenous Rac1 and Cdc42 were temporarily activated at 15 and 30 min after HSV-1 infection. When constitutively active Cdc42 or Rac1 mutants were expressed transiently, a significant decrease in infectivity was observed, whereas expression of RhoA mutants had no influence. Furthermore, dominant-negative Cdc42 led to decreased infectivity, whereas dominant-negative Rac1 had no effect. So far, the study of potential effectors indicated that Rac1/Cdc42 mutants inhibited infectivity independently of p21-activated kinase (Pak1). The inhibitory effect of Rac1/Cdc42 mutant expression on HSV-1 infection was characterized further and it was found that binding, internalization and transport of HSV-1 were not affected by expression of Rac1/Cdc42 mutants. Thus, these results provide the first evidence for a role of Rac1/Cdc42 signalling during early HSV-1 infection and suggest a mechanism relying on virus-induced regulation of Rac1/Cdc42 activities.
Hoppe
Sven
S
Max-Planck-Institute for Neurological Research, University of Cologne, Cologne, Germany.
Schelhaas
Mario
M
Max-Planck-Institute for Neurological Research, University of Cologne, Cologne, Germany.
Jaeger
Verena
V
Max-Planck-Institute for Neurological Research, University of Cologne, Cologne, Germany.
Liebig
Timo
T
Max-Planck-Institute for Neurological Research, University of Cologne, Cologne, Germany.
Petermann
Philipp
P
Department of Neurology, University of Cologne, Cologne, Germany.
Knebel-Mörsdorf
Dagmar
D
Department of Neurology, University of Cologne, Cologne, Germany.|Max-Planck-Institute for Neurological Research, University of Cologne, Cologne, Germany.
D000199:Actins / Q000032:analysis; D000818:Animals; D002457:Cell Extracts / Q000737:chemistry; D002460:Cell Line; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000821:virology*; D005434:Flow Cytometry; D018259:Herpesvirus 1, Human / Q000502:physiology*; D008856:Microscopy, Fluorescence; D015398:Signal Transduction; D053585:Virus Attachment; D053586:Virus Internalization; D020764:cdc42 GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D000199:Actins; D002457:Cell Extracts; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein