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).
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