Oyster viperin retains direct antiviral activity and its transcription occurs via a signalling pathway involving a heat-stable haemolymph protein

Abstract

Little is known about the response of non-model invertebrates, such as oysters, to virus infection. The vertebrate innate immune system detects virus-derived nucleic acids to trigger the type I IFN pathway, leading to the transcription of hundreds of IFN-stimulated genes (ISGs) that exert antiviral functions. Invertebrates were thought to lack the IFN pathway based on the absence of IFN or ISGs encoded in model invertebrate genomes. However, the oyster genome encodes many ISGs, including the well-described antiviral protein viperin. In this study, we characterized oyster viperin and showed that it localizes to caveolin-1 and inhibits dengue virus replication in a heterologous model. In a second set of experiments, we have provided evidence that the haemolymph from poly(I : C)-injected oysters contains a heat-stable, proteasesusceptible factor that induces haemocyte transcription of viperin mRNA in conjunction with upregulation of IFN regulatory factor. Collectively, these results support the concept that oysters have antiviral systems that are homologous to the vertebrate IFN pathway.

Transgenerational plasticity and antiviral immunity in the Pacific oyster (Crassostrea gigas) against Ostreid herpesvirus 1 (OsHV-1)

“…In support of maternal provisioning is the up-regulation of antiviral effector genes, including viperin, in the eggs of C. gigas following stimulation with poly(I:C) (Figure 4). Viperin has been shown to be induced by poly(I:C) treatment via a hemolymph cytokine and to play a direct role in oyster antiviral defense (Green et al, 2015c). Maternal provisioning is consistent with a previous study on the scallop Chlamys farreri, where mothers stimulated with heat-killed Vibrio transfer antibacterial proteins to their offspring via the egg (Yue et al, 2013).…”

Viruses infecting marine molluscs

“…Due to the absence of IFN encoded in their genomes, invertebrates were thought to lack the interferon (IFN) pathway. However, Green et al (2015b) have explored the role of the viperin in oysters. Viperin, an antiviral protein, is often described in different organisms.…”

“…The capacity of adult oysters to inhibit and control the apoptotic process could be essential for survival. Green et al (2015) investigated the role of the apoptosis during an OsHV-1 infection in C. gigas. They have shown that the extrinsic apoptosis pathway related to Tumor Necrosis Factor (TNF) was induced in response to the viral infection, but they failed to observe evidence of apoptosis using a combination of biochemical and molecular assays.…”

“…IAPs encoded by OsHV-1 were highly expressed during the acute stage of infection and may explain why they didn't observe evidence of apoptosis. However, C.gigas must have an alternative mechanism to apoptosis for clearing OsHV-1 from infected gill cells as they observed a reduction in viral DNA between 27 and 54 h post-infection (Green et al, 2015). Autophagy is another form of programmed cell death.…”

“…Many studies on oyster gene expression have shown that they can recognize virus-associated molecular patterns to induce a systemic transcriptional response that is capable of controlling OsHV-1 infection and replication (Green et al, 2015;Green et al, 2014a, b;Green and Montagnani, 2013;Renault et al, 2012, Segarra et al, b and c). Molluscs expressing small interference RNA molecules targeting specific viruses could be of great value to reduce the impact of herpesviruses such as OsHV-1 or AbHV as they would be inherently resistant to the pathogen.…”