Targeting of viral proteins to axons and dendrites

Sammanfattning: In the thesis distribution of different proteins of enveloped and non-enveloped viruses was studied in neurons, which are polarized cells with an axonal and a somatodendritic domain. Such studies may give better insight not only into virus spread within neuronal populations and selective changes in infected neurons as a consequence of the spread, but they may also contribute to an understanding of the basic sorting mechanisms, which are responsible for asymmetric targeting of macromolecules to the pre- 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 vitro; and 2) Investigate effects of the viruses on neurons with special reference to the cytoskeleton. The following conclusions can be presented: 1) Sendai virus and retrovirus, are localized asymmetrically, while the components of rotavirus appear symmetrically in neurons. The asymmetric distribution of the Sendai virus membrane proteins to axons and retrovirus membrane proteins to somatodendritic domains correspond to an earlier described sorting of these proteins to apical and basolateral epithelial plasma membrane domains, respectively; 2) The components of different viruses participate in different types of intracellular interactions in neurons. The membrane and cytosolic proteins of Sendai virus appeared to be segregated within infected neurons. Rotavirus proteins also appeared segregated in neurons and selective interactions between rotavirus cytosolic proteins and host cell cytoskeleton proteins were shown. In the case of retrovirus, however, a specific intraneuronal interaction between env protein and gag may occur and it is suggested that an asymmetric distribution of gag is determined by the env protein; and 3) Components of different viruses can be used as intraneuronal markers to study basic mechanisms of intracellular sorting and transport in nerve cells and vice versa highly polarized neurons can also be utilized for studies on interactions between different viral proteins.