Session topic

17:50–17:55

Title: Importin α5 restricts herpesvirus infection in fibroblasts by promoting lysosomal degradation of incoming viral particles
ID: PS 25
Type: Poster session
Talk time: 3 + 2 min
Session: Poster session 1
Receptors and entry

Speaker: Katinka Döhner (Hannover/DE)


Abstract - Text

Abstract text (incl. references and figure legends)

The 6 murine and 7 human importin αs mediate nuclear import of transcription factors to regulate gene expression including that of interferon-stimulated and lysosome-regulating genes. Herpes simplex virus (HSV-1) does not require importin α1 (RCH family) for microtubule-mediated transport of incoming capsids to the nuclear pores or for genome release into the nucleus, but for the nuclear import of viral proteins contributing to transcription, DNA replication, and capsid assembly in fibroblasts and neurons (Döhner, Ramos-Nascimento, Bialy 2018, PPath).


Here, we addressed the roles of importin α5 and α7 (SRP family) for HSV-1 infection. Importin α5 restricted nuclear targeting of incoming capsids and HSV-1 gene expression in murine and human fibroblasts, especially after high ectopic expression. Furthermore, nuclear capsid targeting and viral gene expression were impaired in an importin α7 deficient murine embryonic fibroblast cell line with elevated (MEF-Imp α7-/--I) but not in one with physiological importin α5 levels (MEF-Imp α7-/--II). MEF-Imp α7-/--I contained more large acidic organelles, especially large lysosomes. In MEF-wt and -Imp α5-/- incoming HSV-1 particles were targeted to a certain extent to acidic organelles, but the lysosomes of the MEF-Imp α7-/--I contained much more HSV-1 particles. This lysosomal HSV-1 fraction decreased over time unless we had inhibited endosomal acidification. In murine neurons, in contrast to fibroblasts, importin α5 restricted neither nuclear capsid targeting nor viral gene expression. Since importin αs of the SRP family link several NLS-exposing host cargoes to dynein, we measured retrograde axonal transport of incoming HSV-1 capsids by live cell imaging. However, capsids were as motile in the absence of importin α5, α7 or both as in their presence.


Our data show that importin α5 and α7 were not required for dynein-mediated microtubule transport of incoming HSV-1 capsids. Furthermore, in fibroblasts importin α5 rather restricted incoming HSV-1 particles by promoting their lysosomal degradation. Our results suggest that importin α5 can promote innate immune responses and lysosomal degradation, especially if expressed at elevated levels. This enhanced targeting to lysosomes impaired HSV-1 infection of fibroblasts but not of neurons; presumably, because HSV-1 enters neurons by fusion at the plasma membrane but fibroblast by fusion with endosomal membranes.