Endoplasmic Stress Affects the Coinfection of Leishmania Amazonensis and the Phlebovirus (Bunyaviridae) Icoaraci

José V Dos Santos; Patricia F Freixo; Áislan de C Vivarini; Jorge M Medina; Lucio A Caldas; Marcia Attias; Karina L Dias Teixeira; Teresa Cristina C Silva; Ulisses G Lopes

doi:10.3390/v14091948

Endoplasmic Stress Affects the Coinfection of Leishmania Amazonensis and the Phlebovirus (Bunyaviridae) Icoaraci

Viruses. 2022 Sep 2;14(9):1948. doi: 10.3390/v14091948.

Authors

José V Dos Santos¹, Patricia F Freixo¹, Áislan de C Vivarini¹, Jorge M Medina¹, Lucio A Caldas², Marcia Attias², Karina L Dias Teixeira³, Teresa Cristina C Silva¹, Ulisses G Lopes¹

Affiliations

¹ Laboratory of Molecular Parasitology, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
² Laboratory of Ultrastructure Hertha Meyer Cellular, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
³ Department of Cell Biology, University of Virginia, Pinn Hall, Charlottesville, VA 22908, USA.

Abstract

Viral coinfections can modulate the severity of parasitic diseases, such as human cutaneous leishmaniasis. Leishmania parasites infect thousands of people worldwide and cause from single cutaneous self-healing lesions to massive mucosal destructive lesions. The transmission to vertebrates requires the bite of Phlebotomine sandflies, which can also transmit Phlebovirus. We have demonstrated that Leishmania infection requires and triggers the Endoplasmic stress (ER stress) response in infected macrophages. In the present paper, we tested the hypothesis that ER stress is increased and required for the aggravation of Leishmania infection due to coinfection with Phlebovirus. We demonstrated that Phlebovirus Icoaraci induces the ER stress program in macrophages mediated by the branches IRE/XBP1 and PERK/ATF4. The coinfection with L. amazonensis potentiates and sustains the ER stress, and the inhibition of IRE1α or PERK results in poor viral replication and decreased parasite load in macrophages. Importantly, we observed an increase in viral replication during the coinfection with Leishmania. Our results demonstrated the role of ER stress branches IRE1/XBP1 and PERK/ATF4 in the synergic effect on the Leishmania increased load during Phlebovirus coinfection and suggests that Leishmania infection can also increase the replication of Phlebovirus in macrophages.

Keywords: ER stress; Leishmania; Phlebovirus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Coinfection*
Endoribonucleases
Humans
Leishmania*
Leishmaniasis*
Orthobunyavirus*
Phlebovirus*
Protein Serine-Threonine Kinases

Substances

Protein Serine-Threonine Kinases
Endoribonucleases

Grants and funding

The Fundação Carlos Chagas Filho de Amparo a Pesquisa gave financialsupport through the grants: FAPERJ/APQ1(E-26/211557/2015-16); CNE- E-26/203089/226392; E-26-210535- 248477; E-26/210279(241548); (E-26/211320); Rede de Pesquisa em Doenças Negligenciadas, FAPERJ (E-26/100021); and EDITAL FAPERJ/PENSARIO (E-26/210914). We are also indebted to the National Council for Research (CNPq) for their support. The agencies had no role in the study design, data collection, interpretation, or the decision to submit the work for publication.