Virus Research 198 (2015) 44–52 Contents lists available at ScienceDirect Virus Research j ourna l ho me pa g e: www.elsevier.com/locate/virusres Negative effect of heat shock on feline calicivirus release from infected cells is associated with the control of apoptosis Cristal Alvarez-Sanchez a,1 , Clotilde Cancio-Lonches a,1 , José Eduardo Mora-Heredia a , Juan Carlos Santos-Valencia a , Oscar Salvador Barrera-Vázquez a , Martha Yocupicio-Monroy b , Ana Lorena Gutiérrez-Escolano a,∗ a Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del IPN, México City, Mexico b Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, México City, Mexico a r t i c l e i n f o Article history: Received 31 August 2014 Received in revised form 22 December 2014 Accepted 7 January 2015 Available online 17 January 2015 Keywords: Feline calicivirus Heat shock Apoptosis a b s t r a c t FCV infection causes rapid cytopathic effects, and its replication results in the induction of apoptosis changes in cultured cells. It is well established that the survival of apoptotic cells can be enhanced by the expression of heat-shock proteins (Hsp) to prevent damage or facilitate recovery. Hsps can act as molecular chaperones, but they can also have anti-apoptotic roles by binding to apoptotic proteins and inhibiting the activation of caspases, the primary mediators of apoptosis. Because apoptosis occurs during FCV infection and heat shock (HS) treatment has a cytoprotective role due to the expression of Hsps, we studied the effect of the HS response to hyperthermia during FCV infection in cultured cells. We found that FCV infection does not inhibit the expression of Hsp70 induced by HS and that non-structural and structural protein synthesis was not modified during HS treatment. However, HS caused a delay in the appearance of a cytopathic effect in infected cells, as well as a reduction in the extracellular but not in the cell-associated viral yield. This antiviral effect of HS correlates with the inhibition of caspase- 3 activation. Thus, the HS-induced reduction in virus production appeared to be associated with the control of apoptosis, supporting previous data that indicate that apoptosis is necessary for FCV release. © 2015 Elsevier B.V. All rights reserved. 1. Introduction The Caliciviridae family is composed of small, nonenveloped, positive-strand RNA viruses, including numerous pathogens that infect a broad range of vertebrate hosts and cause several diseases that affect animals and humans. In particular, calicivirus infec- tions in humans are the leading cause of gastroenteritis worldwide (Koo et al., 2010). Studies investigating the biology and pathogen- esis of these viruses are still restricted to viruses that replicate in cell culture or for which appropriate animal models are avail- able (Sosnovtsev et al., 2003). One of the most valuable models for understanding calicivirus biology is feline calicivirus (FCV) (Pesavento et al., 2008; Vashist et al., 2009). Although FCV causes ∗ Corresponding author at: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del IPN, Av. IPN 2508. Col. San Pedro Zacatenco, México, D.F. C.P. 07360, México. Tel.: +52 1 555747 3800x5655; fax: +52 1 555747 3377. E-mail address: alonso@cinvestav.mx (A.L. Gutiérrez-Escolano). 1 These authors contributed equally to this work. an infection in cats that produces signs of oral ulceration and/or upper respiratory disease, its ability to grow in vitro and the possi- bility to be genetically manipulated, have contributed to the study of the molecular mechanism of calicivirus translation and genome replication (Sosnovtsev and Green, 1995; Vashist et al., 2009). As with many other viruses, FCV has evolved sophisticated strategies to exploit the metabolic machinery of the host cell for its own multiplication, such as hijacking the host transcrip- tional/translational machinery (Kuyumcu-Martinez et al., 2004; Willcocks et al., 2004) and controlling cellular signaling and apop- totic pathways (Al-Molawi et al., 2003; Natoni et al., 2006; Roberts et al., 2003; Sosnovtsev et al., 2003). FCV infection causes rapid cytopathic effects, and its replication results in the induction of apoptosis in cultured cells. Apoptosis is a highly coordinated process for controlling cell homeostasis in multicellular organisms in response to a wide range of stimuli, including stress and viral infections (Vaux and Strasser, 1996). A number of viruses are known to express proteins that inhibit apoptosis (Garnett and Duerksen-Hughes, 2006; Liu et al., 2012; McNees and Gooding, 2002; O’brien, 1998). However, for some other viruses, and probably for FCV, apoptosis facilitates the http://dx.doi.org/10.1016/j.virusres.2015.01.003 0168-1702/© 2015 Elsevier B.V. All rights reserved.