Most cited article - PubMed ID 29352310
Leishmania proteophosphoglycans regurgitated from infected sand flies accelerate dermal wound repair and exacerbate leishmaniasis via insulin-like growth factor 1-dependent signalling
In this work, we describe the first Leishmania-infecting leishbunyavirus-the first virus other than Leishmania RNA virus (LRV) found in trypanosomatid parasites. Its host is Leishmaniamartiniquensis, a human pathogen causing infections with a wide range of manifestations from asymptomatic to severe visceral disease. This virus (LmarLBV1) possesses many characteristic features of leishbunyaviruses, such as tripartite organization of its RNA genome, with ORFs encoding RNA-dependent RNA polymerase, surface glycoprotein, and nucleoprotein on L, M, and S segments, respectively. Our phylogenetic analyses suggest that LmarLBV1 originated from leishbunyaviruses of monoxenous trypanosomatids and, probably, is a result of genomic re-assortment. The LmarLBV1 facilitates parasites' infectivity in vitro in primary murine macrophages model. The discovery of a virus in L.martiniquensis poses the question of whether it influences pathogenicity of this parasite in vivo, similarly to the LRV in other Leishmania species.
- Keywords
- Bunyavirales, Leishmania martiniquensis, leishbunyavirus,
- MeSH
- Phylogeny * MeSH
- Genome, Viral * MeSH
- Leishmania pathogenicity virology MeSH
- Macrophages parasitology MeSH
- Mice MeSH
- Open Reading Frames MeSH
- Reassortant Viruses MeSH
- RNA-Dependent RNA Polymerase MeSH
- RNA Viruses classification genetics MeSH
- High-Throughput Nucleotide Sequencing MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- RNA-Dependent RNA Polymerase MeSH
Leishmania rely heavily on glycans to complete their digenetic life cycle in both mammalian and phlebotomine sand fly hosts. Leishmania promastigotes secrete a proteophosphoglycan-rich gel (Promastigote Secretory Gel, PSG) that is regurgitated during transmission and can exacerbate infection in the skin. Here we explored the role of PSG from natural Leishmania-sand fly vector combinations by obtaining PSG from Leishmania (L.) major-infected Phlebotomus (P.) papatasi and P. duboscqi and L. tropica-infected P. arabicus. We found that, in addition to the vector's saliva, the PSG from L. major and L. tropica potently exacerbated cutaneous infection in BALB/c mice, improved the probability of developing a patent cutaneous lesion, parasite growth and the evolution of the lesion. Of note, the presence of PSG in the inoculum more than halved the prepatent period of cutaneous L. tropica infection from an average of 32 weeks to 13 weeks. In addition, L. major and L. tropica PSG extracted from the permissive experimental vector, Lutzomyia (Lu.) longipalpis, also exacerbated infections in mice. These results reinforce and extend the hypothesis that PSG is an important and evolutionarily conserved component of Leishmania infection that can be used to facilitate experimental infection for drug and vaccine screening.
- Keywords
- Cutaneous leishmaniasis, Leishmania, Leishmania major, Leishmania mexicana, Leishmania tropica, PSG, sand fly, transmission, zoonoses,
- MeSH
- Skin drug effects parasitology pathology MeSH
- Leishmania major chemistry MeSH
- Leishmania tropica chemistry MeSH
- Leishmaniasis, Cutaneous parasitology pathology MeSH
- Membrane Proteins administration & dosage chemistry MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Parasite Load MeSH
- Phlebotomus parasitology MeSH
- Proteoglycans administration & dosage chemistry MeSH
- Protozoan Proteins administration & dosage chemistry MeSH
- Saliva MeSH
- Symptom Flare Up MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Membrane Proteins MeSH
- Ppg1 protein, Leishmania MeSH Browser
- Proteoglycans MeSH
- Protozoan Proteins MeSH