%0 Journal Article %A Hoppe, Sven %A Schelhaas, Mario %A Jaeger, Verena %A Liebig, Timo %A Petermann, Philipp %A Knebel-Mörsdorf, Dagmar %T Early herpes simplex virus type 1 infection is dependent on regulated Rac1/Cdc42 signalling in epithelial MDCKII cells %D 2006 %J Journal of General Virology, %V 87 %N 12 %P 3483-3494 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.82231-0 %I Microbiology Society, %X 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. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.82231-0