A Virion-Associated Protein Kinase Induces Apoptosis

Abstract

Apoptosis and inhibition of host gene expression are often associated with virus infections. Many viral polypeptides modulate apoptosis by direct interaction with highly conserved apoptotic pathways. Some viruses induce apoptosis during late stages of the infection cycle, while others inhibit apoptosis to facilitate replication or maintain persistent infection. In previous work, we showed that Chilo iridescent virus (CIV) or CIV virion protein extract induces apoptosis in spruce budworm and cotton boll weevil cell cultures. Here, we characterize the product of a CIV gene (iridovirus serine/threonine kinase; istk) with signature sequences for S/T kinase and ATP binding. ISTK appears to belong to the superfamily, vaccinia-related kinases (VRKs). The istk gene was expressed in Pichia pastoris vectors. Purified ISTK (48 kDa) exhibited S/T kinase activity. Treatment with ISTK induced apoptosis in budworm cells. A 35-kDa cleavage product of ISTK retaining key signature sequences was identified during purification. Pichia-expressed 35-kDa polypeptide, designated iridoptin, induced apoptosis and inhibition of host protein synthesis in budworm and boll weevil cells. A mutation in the ATP-binding site eliminated both kinase and apoptosis activity of iridoptin, suggesting that kinase activity is essential for induction of apoptosis. Analysis with custom antibody confirmed that ISTK is a structural component of CIV particles. This is the first demonstration of a viral kinase inducing apoptosis in any virus-host system and the first identification of a factor inducing apoptosis or host protein shutoff for the family Iridoviridae.

Temporal proteomic analysis and label-free quantification of viral proteins of an invertebrate iridovirus

“…A recent study on the serine/threonine protein kinase 389L (so-called iridoptin) suggested that this kinase is associated with the IIV-6 virion structure. The purified form of the protein induced apoptosis in insect cells (Chitnis et al, 2011). Viral kinases are also potential antiviral drug targets, as they may play crucial roles to guarantee successful viral infection.…”

Baculovirus-induced insect behaviour: from genes to brains

“…Many viruses carry genes that are involved in inducing apoptosis in host-derived cell lines (Chitnis et al, 2011;Clem, 2001;Han et al, 2009;Prikhod'ko and Miller, 1996;Suderman et al, 2008), such as the ptp-h2 gene from MdBV, which induces apoptosis in Sf21 cells (Suderman et al, 2008). The baculovirus SeMNPV carries a protein tyrosine phosphatase gene (ptp2) which contains the same catalytic domain as ptp-h2, therefore, we tested whether SeMNPV ptp2 has a pro-apoptotic function as well.…”

“…By inducing apoptosis virus replication is terminated, thus reducing progeny virus production (Clem, 2005). In contrast, some viruses induce apoptosis in certain host cells to suppress the host immune system and/or enhance virus dissemination (Chitnis et al, 2011;Ni et al, 2017;Suderman et al, 2008). For example, the polydnavirus Microplitis demolitor bracovirus (MdBV) induced apoptosis in specific hemocytes of Spodoptera frugiperda caterpillars and this activity contributed to the immunosuppression of the host (Suderman et al, 2008).…”

“…Viruses have developed a range of strategies to counteract host-induced apoptosis (Kvansakul, 2017), including the expression of anti-apoptotic genes. On the other hand, some viruses have been found to actively induce apoptosis in their host in order to suppress the host immune system and/or enhance virus dissemination (Chitnis et al, 2011;Suderman et al, 2008). For example, it was found that the polydnavirus Microplitis demolitor bracovirus (MdBV) induced apoptosis in immune cells of Spodoptera frugiperda caterpillars and that this activity contributed to the immunosuppression of the host (Suderman et al, 2008).…”

“…For example, it was found that the polydnavirus Microplitis demolitor bracovirus (MdBV) induced apoptosis in immune cells of Spodoptera frugiperda caterpillars and that this activity contributed to the immunosuppression of the host (Suderman et al, 2008). Several viral genes and proteins have been found to induce pro-apoptotic effects in host-derived cell lines (Anasir et al, 2017;Chitnis et al, 2011;Schultz-Cherry et al, 2001;Suderman et al, 2008). For example, Suderman et al (Suderman et al, 2008) found that the protein tyrosine phosphatase-H2 ( Baculoviruses are arthropod-specific viruses with a circular, double-stranded DNA genome (Williams et al, 2017).…”