The Solute Carrier Transporter SLC15A3 Participates in Antiviral Innate Immune Responses against Herpes Simplex Virus-1

Abstract

The innate immune response is the first line defense against viral infections. Novel genes involved in this system are continuing to emerge. SLC15A3, a proton-coupled histidine and di-tripeptide transporter that was previously found in lysosomes, has been reported to inhibit chikungunya viral replication in host cells. In this study, we found that SLC15A3 was significantly induced by DNA virus herpes simplex virus-1(HSV-1) in monocytes from human peripheral blood mononuclear cells. Aside from monocytes, it can also be induced by HSV-1 in 293T, HeLa cells, and HaCaT cells. Overexpression of SLC15A3 in 293T cells inhibits HSV-1 replication and enhances type I and type III interferon (IFN) responses, while silencing SLC15A3 leads to enhanced HSV-1 replication with reduced IFN production. Moreover, we found that SLC15A3 interacted with MAVS and STING and potentiated MAVS- and STING-mediated IFN production. These results demonstrate that SLC15A3 participates in anti-HSV-1 innate immune responses by regulating MAVS- and STING-mediated signaling pathways.

Comparative Analysis of Public RNA-Sequencing Data from Human Intestinal Enteroid (HIEs) Infected with Enteric RNA Viruses Identifies Universal and Virus-Specific Epithelial Responses

“…However, within the shared DEGs, virus-specific induction patterns were also observed. For example, we observed that the ISGs 2 -5 -oligoadenylate synthetase-like (OASL) and Interferon Induced Protein 44 (IFI44), as well as the Solute Carrier Family 15 Member 3 (SLC15A3), which potentiates MAVS-and STING-mediated IFN production [30], showed a stronger up-regulation in the norovirusinfected ileal HIEs compared to astrovirus-and rotavirus-infected ones (Figure 4B). On the other hand, IFIT1 showed greater up-regulation in the rotavirus dataset versus either the norovirus or astrovirus datasets.…”

Peroxisomes in Immune Response and Inflammation

“…RLR-mediated type III interferon expression can be induced by various viruses, including reoviruses, Sendai- and dengue viruses [137]. Recently, SLC15A3, a proton-coupled histidine and di-tripeptide transporter previously found in lysosomes, has been reported to be partially localized in peroxisomes [138]. While known to inhibit chikungunya viral replication, SLC15A3 was demonstrated to inhibit HSV-1 replication and enhance type I and type III interferon responses.…”

Comparative analysis of public RNA-sequencing data from human intestinal enteroid (HIEs) infected with enteric RNA viruses identifies universal and virus-specific epithelial responses

“…However, within the shared DEGs, virus-specific induction patterns were also observed. For example, we observed that the two ISGs 2’-5’-oligoadenylate synthetase (OASL), Interferon Induced Protein 44 (IFI44) and the Solute Carrier Family 15 Member 3 (SLC15A3), which potentiates MAVS- and STING-mediated IFN production [18], showed a stronger up-regulation in the norovirus-infected ileal-HIEs compared to astrovirus and rotavirus infection (Figure 4B) . On the other hand, IFN Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) showed greater up-regulation in the rotavirus dataset versus either norovirus or astrovirus datasets.…”