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Tegument proteins are sequentially released, with the inner tegument proteins presumably interacting with host motor proteins [44].
The most direct explanation for the ORF75c− phenotype would therefore be that ORF75c links the viral capsid to host motor proteins for transport to nuclear pores.
In regions of GDNF delivery many host motor neurons were labeled with GDNF suggesting active uptake of the protein into surviving motor neurons (Figure 2D).
Since in the current ex vivo gene therapy approach used hNPC to deliver the protein, host motor neurons did not need to be exposed to lentivirus which may have increased the chance of neuroprotection.
We suggest that GDNF, perhaps in combination with other factors secreted by hNPC, activates cell protection pathways within host motor neurons that may be linked to anti-apoptotic proteins [39], [40].
Human embryonic germ cell-derived embryoid bodies secrete BDNF and transforming growth factor α (TGF-α) that enhance neuronal survival and reafferentation of host motor neurons when transplanted into rats with diffuse motor neuron paralysis [2].
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