Targeting of viral proteins to axons and dendrites

Sammanfattning: Tn the thesis distribution of different proteins of enveloped and non-enveloped viruseswas studied in neurons, which are polarized cells with an axonal and a somatodendriticdomain. Such studies may give better insight not only into virus spread withinneuronal populations and selective changes in infected neurons as a consequence of thespread, but they may also contribute to an understanding of the basic sortingmechanisrns, which are responsible for asymmetric targeting of macromolecules to thepre- and postsynaptic regions in a nerve cell.The aims of the studies were:1) To examine transport and targeting of the components of three different viruses,i.e. Sendai virus, C-type retrovirus and rotavirus in neurons in vitro2) Investigate effects of the viruses on neurons with special reference to thecytoskeleton.The following conclusions can be praent:1. Sendai virus and retrovirus, are localized asymmetrically, while the components ofrotavirus appear symmetrically in neurons. The asymmetric distribution of the Sendaivirus membrane proteins to axons and retrovirus membrane proteins tosomatodendritic domains correspond to an earlier described sorting of these proteinsto apical and basolateral epithelial plasma membrane domains, respectively.2. The components of different viruses participate in different types of intracellularinteractions in neurons. The membrane and cytosolic proteins of Sendai virus appearedto be segregated within infected neurons. Rotavirus proteins also appeared segregatedin neurons and selective interactions between rotavirus cytosolic proteins and host cellcytoskeleton proteins were shown. In the case of retrovirus, however, a specificintraneuronal interaction between env protein and gag may occur and it is suggestedthat an asymmetric distribution of gag is determined by the env protein.3. Components of different viruses can be used as intraneuronal markers to study basicmechanisms of intracellular sorting and transport in nerve cells and vice versa highlypolarized neurons can also be utilized for studies on interactions between different viralproteins.