Vesa Aho, Sami Salminen, Salla Mattola , Alka Gupta, Felix Flomm, Beate Sodeik, Jens B Bosse, Maija Vihinen-Ranta, Infection-induced chromatin modifications facilitate translocation of herpes simplex virus capsids to the inner nuclear membrane, PLoS Pathog, 2021
Herpes simplex virus type 1 is a DNA virus that is studied intensively due to its high prevalence in humans, its ability to cause many diseases upon lytic replication or to evade the immune system in a latent state, and its potential use in oncolytic and immunotherapeutic applications. The nuclear replication of herpes simplex virus type 1 leads to the emergence of viral replication compartments together with relocalization and condensation of the host cell chromatin to the nuclear periphery. The reorganization of the host chromatin potentially hampers the intranuclear transport and nuclear egress of newly assembled progeny capsids. Nuclear capsids move by diffusion prior to their viral nuclear egress complex mediated exit through the nuclear envelope. However, it is not understood how the capsids travel through the chromatin network. The studies of Vihinen Ranta group show that infection induced changes in chromatin architecture enhance nuclear diffusion of capsids at late infection, and that this transport is the rate limiting step in the nuclear egress of the virus. Understanding the kinetics of capsid translocation in the nucleus is of fundamental interest in the field of DNA virus research because it explains how viruses are able to move in the chromatin before their nuclear egress.
The group of Vihinen-Ranta is focused on understanding the mechanisms of nuclear transport and intranuclear mobility of viruses in order to understand the biological process of infection. They use a range of microscope techniques, including soft Xray microscopy, to image viruses in cells, and look at how they interact with cells during replication, such as nuclear virus interactions and dynamics of the viral capsids.