AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 1(4):367-380,2009

Original Article
Induction of HSP70 by Hantavirus infection suppresses the interaction
of nucleocapsid protein in Vero E6 cells

Lu Yu, Ling Ye, Rong Zhao, Yan Fang Liu, Ji Li, Shou Jing Yang

Department of Pathology, Xi Jing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China, and
Center for Cardiovascular Research and Alternative Medicine, Division of Pharmaceutical Sciences, University of
Wyoming, Laramie, Wyoming 82071, USA

Received June 18, 2009; accepted June, 2009; available online June, 2009

Abstract: Hantavirus infection is known to induce innate immune responses in host cells, however, whether they
stimulate synthesis of stress proteins, particular associations of viral and stress proteins, is entirely unknown.
We have initiated an investigation using Vero E6 cells infected with Hantaan 76-118 (HTNV) to examine the
individual contribution of HTV infection to heat shock response. We found that HTNV infection rapidly induced
HSP70 expression in Vero E6 cells, which undergone a nucleo-cytoplasmic shuttle, and lasted for more than 3 d.
The increased HSP70 protein was preceded by induction of HSP70 mRNA. The physical association of HSP70
with HTNV nucleocapsid protein (NP) in infected cells was demonstrated by co-localization and
immunoprecipation. Furthermore, Vero E6 cells that constitutively overexpress HSP70 after stable transfection
with HSP70 gene, when infected with HTNV, showed selectively reduced NP synthesis. Therefore, our findings
suggest an active role for HSP70 in the control of the level of viral structural proteins, possibly involving in virus
assembly by binding of NP to HSP70, on other side, however, overexpression of HSP70 does not favor viral
propagation. (AJTR906003).

Key words: Hantavirus infection, nucleocapsid protein, virus replication, HSP70 heat-shock proteins,
transcription, gene transfection

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Address all correspondence to:
Shou Jing Yang, M.D., Ph.D.
Department of Pathology
Fourth Military Medical University
No. 17 Chang Le Xi Road
Xi’an, Shaanxi 710032
Tel: (011) 86 29-84773527
Fax: (011) 86 29-84773624
e-mail:
yangsj@fmmu.edu.cn