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Early herpes simplex virus type 1 infection is dependent on regulated Rac1/Cdc42 signalling in epithelial MDCKII cells

Sven Hoppe^1,,

Mario Schelhaas^1,,

¹ Max-Planck-Institute for Neurological Research, University of Cologne, Cologne, Germany
² Department of Neurology, University of Cologne, Cologne, Germany

Correspondence
Dagmar Knebel-Mörsdorf
dagmar.moersdorf{at}uni-koeln.de

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.

These authors contributed equally to this work.

Present address: German Cancer Research Centre, D-69120 Heidelberg, Germany.

Present address: Institute of Biochemistry, Swiss Institute of Technology Zurich, CH-8093 Zurich, Switzerland.

||Present address: Centre of Biochemistry, Medical Faculty of the University of Cologne, D-50931 Cologne, Germany.

¶Present address: Molecular and Cellular Medicine Section, Imperial College London, London SW7 2AZ, UK.

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