C-terminal lysosome targeting domain of CD63 modifies cellular localization of rabies virus glycoprotein


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Abstract

The glycoprotein of rabies virus is the central antigen elicited the immune response to infection; therefore, the majority of developing anti-rabies vaccines are based on this protein. In order to increase the efficacy of DNA immunogen encoding rabies virus glycoprotein, the construction of chimeric protein with the CD63 domain has been proposed. The CD63 is a transmembrane protein localized on the cell surface and in lysosomes. The lysosome targeting motif GYEVM is located at its C-terminus. We used the domain that bears this motif (c-CD63) to generate chimeric glycoprotein in order to relocalize it into lysosomes. Here, it was shown that, in cells transfected with plasmid that encodes glycoprotein with c-CD63 motif at the C-terminus, the chimeric protein was predominantly observed in lysosomes and at the cell membrane where the unmodified glycoprotein is localized in the endoplasmic reticulum and at the cell surface. We suppose that current modification of the glycoprotein may improve the immunogenicity of anti-rabies DNA vaccines due to more efficient antibody production.

About the authors

E. S. Starodubova

Engelhardt Institute of Molecular Biology

Author for correspondence.
Email: estarodubova@yandex.ru
Russian Federation, Moscow, 119991

Y. V. Kuzmenko

Engelhardt Institute of Molecular Biology

Email: estarodubova@yandex.ru
Russian Federation, Moscow, 119991

A. A. Latanova

Engelhardt Institute of Molecular Biology

Email: estarodubova@yandex.ru
Russian Federation, Moscow, 119991

O. V. Preobrazhenskaya

Engelhardt Institute of Molecular Biology

Email: estarodubova@yandex.ru
Russian Federation, Moscow, 119991

V. L. Karpov

Engelhardt Institute of Molecular Biology

Email: estarodubova@yandex.ru
Russian Federation, Moscow, 119991

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