The Association of Leishmania RNA Viruses with metastatic or mucocutaneous Leishmaniasis in South America

Abstract

Leishmaniasis is a spectral disease caused by the Trypanosomatid protozoan parasite Leishmania. One manifestation is a disfiguring mucocutaneous form (MCL) involving dissemination to nasopharyngeal areas and tissue destruction, caused by species from the South American Leishmania subgenus Viannia. We reported previously that metastatic L. guyanensis bear high levels of a novel dsRNA totivirus (LRV1), while non‐metastatic lines have low levels or lack LRV1. LRV1‐infected Leishmania were associated with a hyper‐inflammatory response dependent on the host Toll‐like receptor 3 (TLR3) signaling. Thus, LRV in metastatic parasites subverts the host immune response and promotes dissemination. This is the first parasite factor implicated causally in phenotypes relevant to metastatic mucocutaneous disease, with LRV acting as a ‘parasite within a parasite’. The closely related species L. braziliensis is responsible for the great majority of human MCL. Thus we are surveying L. braziliensis strains to establish the distribution and potential for clinical association(s) of LRVs in parasites taken from humans. Several novel LRVs were identified; these are currently being characterized by virus and genome sequencing, classical virological approaches, and infectivity tests of the LRV‐bearing L. braziliensis in animal models.