Academic Journal
Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis.
| Title: | Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis. |
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| Authors: | Carolina Torturella Rath, Laila Castro Schnellrath, Clarissa R Damaso, Luciana Barros de Arruda, Pedro Fernando da Costa Vasconcelos, Claudia Gomes, Marcia Dalastra Laurenti, Teresa Cristina Calegari Silva, Áislan de Carvalho Vivarini, Nicolas Fasel, Renata Meirelles Santos Pereira, Ulisses Gazos Lopes |
| Source: | PLoS Neglected Tropical Diseases, Vol 13, Iss 6, p e0007500 (2019) |
| Publisher Information: | Public Library of Science (PLoS), 2019. |
| Publication Year: | 2019 |
| Collection: | LCC:Arctic medicine. Tropical medicine LCC:Public aspects of medicine |
| Subject Terms: | Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270 |
| More Details: | BackgroundLeishmania parasites are transmitted to vertebrate hosts by phlebotomine sandflies and, in humans, may cause tegumentary or visceral leishmaniasis. The role of PKR (dsRNA activated kinase) and Toll-like receptor 3 (TLR3) activation in the control of Leishmania infection highlights the importance of the engagement of RNA sensors, which are usually involved in the antiviral cell response, in the fate of parasitism by Leishmania. We tested the hypothesis that Phlebovirus, a subgroup of the Bunyaviridae, transmitted by sandflies, would interfere with Leishmania infection.Methodology/principal findingsWe tested two Phlebovirus isolates, Icoaraci and Pacui, from the rodents Nectomys sp. and Oryzomys sp., respectively, both natural sylvatic reservoir of Leishmania (Leishmania) amazonensis from the Amazon region. Phlebovirus coinfection with L. (L.) amazonensis in murine macrophages led to increased intracellular growth of L. (L.) amazonensis. Further studies with Icoaraci coinfection revealed the requirement of the PKR/IFN1 axis on the exacerbation of the parasite infection. L. (L.) amazonensis and Phlebovirus coinfection potentiated PKR activation and synergistically induced the expression of IFNβ and IL-10. Importantly, in vivo coinfection of C57BL/6 mice corroborated the in vitro data. The exacerbation effect of RNA virus on parasite infection may be specific because coinfection with dengue virus (DENV2) exerted the opposite effect on parasite load.ConclusionsAltogether, our data suggest that coinfections with specific RNA viruses shared by vectors or reservoirs of Leishmania may enhance and sustain the activation of host cellular RNA sensors, resulting in aggravation of the parasite infection. The present work highlights new perspectives for the investigation of antiviral pathways as important modulators of protozoan infections. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1935-2727 1935-2735 |
| Relation: | https://doaj.org/toc/1935-2727; https://doaj.org/toc/1935-2735 |
| DOI: | 10.1371/journal.pntd.0007500 |
| Access URL: | https://doaj.org/article/9bcc055464d548a2afe91ed032f6c070 |
| Accession Number: | edsdoj.9bcc055464d548a2afe91ed032f6c070 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 19352727 19352735 |
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| DOI: | 10.1371/journal.pntd.0007500 |
| Published in: | PLoS Neglected Tropical Diseases |
| Language: | English |