Most cited article - PubMed ID 31640177
Molecular Characterization of Leishmania RNA virus 2 in Leishmaniamajor from Uzbekistan
Leishmania is a genus of the family Trypanosomatidae that unites obligatory parasitic flagellates causing a variety of vector-borne diseases collectively called leishmaniasis. The symptoms range from relatively innocuous skin lesions to complete failures of visceral organs. The disease is exacerbated if a parasite harbors Leishmania RNA viruses (LRVs) of the family Pseudototiviridae. Screening a novel isolate of L. braziliensis, we revealed that it possesses not a toti-, but a bunyavirus of the family Leishbuviridae. To the best of our knowledge, this is a very first discovery of a bunyavirus infecting a representative of the Leishmania subgenus Viannia. We suggest that these viruses may serve as potential factors of virulence in American leishmaniasis and encourage researchers to test leishmanial strains for the presence of not only LRVs, but also other RNA viruses.
- MeSH
- Bunyaviridae classification genetics isolation & purification MeSH
- Phylogeny MeSH
- Leishmania braziliensis * genetics isolation & purification MeSH
- Humans MeSH
- Orthobunyavirus genetics classification isolation & purification physiology MeSH
- RNA Viruses genetics classification isolation & purification MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
RNA viruses play an important role in Leishmania biology and virulence. Their presence was documented in three (out of four) Leishmania subgenera. Sauroleishmania of reptiles remained the only underinvestigated group. In this work, we analyzed the viral occurrence in Sauroleishmania spp. and detected RNA viruses in three out of seven isolates under study. These viruses were of two families-Narnaviridae and Totiviridae. Phylogenetic inferences demonstrated that totiviruses from L. adleri and L. tarentolae group together within a larger cluster of LRV2s, while a narnavirus of L. gymnodactyli appeared as a phylogenetic relative of narnaviruses of Blechomonas spp. Taken together, our work not only expanded the range of trypanosomatids that can host RNA viruses but also shed new light on the evolution and potential routes of viral transmission in these flagellates.
- Keywords
- L. (S.) gymnodactyli, L. (S.) hoogstraali, L. (S.) tarentolae, LRV2, Leishmania (Sauroleishmania) adleri, Narnaviridae,
- MeSH
- Phylogeny MeSH
- Leishmania * MeSH
- Humans MeSH
- Reptiles MeSH
- RNA Viruses * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Leishmania RNA virus 1 (LRV1) is commonly found in South American Leishmania parasites belonging to the subgenus Viannia, whereas Leishmania RNA virus 2 (LRV2) was previously thought to be restricted to the Old-World pathogens of the subgenus Leishmania. OBJECTIVES: In this study, we investigated the presence of LRV2 in strains of Leishmania (L.) infantum, the causative agent of visceral leishmaniasis (VL), originating from different hosts, clinical forms, and geographical regions. METHODS: A total of seventy-one isolates were screened for LRV2 using semi-nested reverse transcription-polymerase chain reaction (RT-PCR) targeting the RNA-dependent RNA polymerase (RdRp) gene. FINDINGS: We detected LRV2 in two L. infantum isolates (CUR268 and HP-EMO) from canine and human cases, respectively. MAIN CONCLUSIONS: To the best of our knowledge, this is the first detection of LRV2 in the New World.
- MeSH
- Leishmania infantum * genetics MeSH
- Leishmaniasis, Visceral * veterinary MeSH
- Humans MeSH
- Dogs MeSH
- RNA-Dependent RNA Polymerase MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Dogs MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Brazil MeSH
- Names of Substances
- RNA-Dependent RNA Polymerase MeSH
The evolution in Leishmania is governed by the opposite forces of clonality and sexual reproduction, with vicariance being an important factor. As such, Leishmania spp. populations may be monospecific or mixed. Leishmania turanica in Central Asia is a good model to compare these two types. In most areas, populations of L. turanica are mixed with L. gerbilli and L. major. Notably, co-infection with L. turanica in great gerbils helps L. major to withstand a break in the transmission cycle. Conversely, the populations of L. turanica in Mongolia are monospecific and geographically isolated. In this work, we compare genomes of several well-characterized strains of L. turanica originated from monospecific and mixed populations in Central Asia in order to shed light on genetic factors, which may drive evolution of these parasites in different settings. Our results illustrate that evolutionary differences between mixed and monospecific populations of L. turanica are not dramatic. On the level of large-scale genomic rearrangements, we confirmed that different genomic loci and different types of rearrangements may differentiate strains originated from mixed and monospecific populations, with genome translocations being the most prominent example. Our data suggests that L. turanica has a significantly higher level of chromosomal copy number variation between the strains compared to its sister species L. major with only one supernumerary chromosome. This suggests that L. turanica (in contrast to L. major) is in the active phase of evolutionary adaptation.
- MeSH
- Genomics MeSH
- Gerbillinae parasitology MeSH
- Leishmania * genetics MeSH
- DNA Copy Number Variations MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Mongolia MeSH
In this work we reviewed historical and recent data on Leishmania spp. infection combining data collected in Turkmenistan, Uzbekistan, Kazakhstan, Kyrgyzstan, Iran, China and Mongolia. We specifically focused on a complex of co-existing species (Leishmania major, Leishmania turanica and Leishmania gerbilli) sharing the same animal reservoirs and vectors. In addition, we analysed the presence of dsRNA viruses in these species and discussed future research directions to identify species-specific traits, which may determine susceptibility of different Leishmania spp. to viral infection.
- Keywords
- Animal reservoir, Leishmania gerbilli, Leishmania major, Leishmania turanica, Leishmaniavirus, central Asia, coinfection, great gerbils,
- MeSH
- Gerbillinae MeSH
- Leishmania major * MeSH
- Leishmaniasis, Cutaneous * epidemiology MeSH
- Leishmaniasis * epidemiology MeSH
- Disease Reservoirs MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Geographicals
- Turkmenistan MeSH
Leishmania spp. are important pathogens causing a vector-borne disease with a broad range of clinical manifestations from self-healing ulcers to the life-threatening visceral forms. Presence of Leishmania RNA virus (LRV) confers survival advantage to these parasites by suppressing anti-leishmanial immunity in the vertebrate host. The two viral species, LRV1 and LRV2 infect species of the subgenera Viannia and Leishmania, respectively. In this work we investigated co-phylogenetic patterns of leishmaniae and their viruses on a small scale (LRV2 in L. major) and demonstrated their predominant coevolution, occasionally broken by intraspecific host switches. Our analysis of the two viral genes, encoding the capsid and RNA-dependent RNA polymerase (RDRP), revealed them to be under the pressure of purifying selection, which was considerably stronger for the former gene across the whole tree. The selective pressure also differs between the LRV clades and correlates with the frequency of interspecific host switches. In addition, using experimental (capsid) and predicted (RDRP) models we demonstrated that the evolutionary variability across the structure is strikingly different in these two viral proteins.
- Keywords
- Leishmaniavirus, coevolution, phylogenomics,
- MeSH
- Leishmania virology MeSH
- Leishmaniasis virology MeSH
- Humans MeSH
- RNA, Viral analysis MeSH
- RNA-Dependent RNA Polymerase genetics MeSH
- RNA Viruses genetics MeSH
- Capsid Proteins genetics MeSH
- Viral Proteins genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- RNA, Viral MeSH
- RNA-Dependent RNA Polymerase MeSH
- Capsid Proteins MeSH
- Viral Proteins MeSH
Euglenozoa is a species-rich group of protists, which have extremely diverse lifestyles and a range of features that distinguish them from other eukaryotes. They are composed of free-living and parasitic kinetoplastids, mostly free-living diplonemids, heterotrophic and photosynthetic euglenids, as well as deep-sea symbiontids. Although they form a well-supported monophyletic group, these morphologically rather distinct groups are almost never treated together in a comparative manner, as attempted here. We present an updated taxonomy, complemented by photos of representative species, with notes on diversity, distribution and biology of euglenozoans. For kinetoplastids, we propose a significantly modified taxonomy that reflects the latest findings. Finally, we summarize what is known about viruses infecting euglenozoans, as well as their relationships with ecto- and endosymbiotic bacteria.
- Keywords
- Diplonemida, Euglenida, Kinetoplastida, microbial eukaryotes, phylogeny, systematics,
- MeSH
- Ecosystem MeSH
- Euglenozoa classification genetics physiology virology MeSH
- Phylogeny MeSH
- Mimiviridae pathogenicity MeSH
- Symbiosis MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Leishmaniasis is widely regarded as a vaccine-preventable disease, but the costs required to reach pivotal Phase 3 studies and uncertainty about which candidate vaccines should be progressed into human studies significantly limits progress in vaccine development for this neglected tropical disease. Controlled human infection models (CHIMs) provide a pathway for accelerating vaccine development and to more fully understand disease pathogenesis and correlates of protection. Here, we describe the isolation, characterization and GMP manufacture of a new clinical strain of Leishmania major. Two fresh strains of L. major from Israel were initially compared by genome sequencing, in vivo infectivity and drug sensitivity in mice, and development and transmission competence in sand flies, allowing one to be selected for GMP production. This study addresses a major roadblock in the development of vaccines for leishmaniasis, providing a key resource for CHIM studies of sand fly transmitted cutaneous leishmaniasis.
- MeSH
- Phylogeny MeSH
- Insect Vectors parasitology MeSH
- Leishmania major genetics growth & development physiology MeSH
- Leishmaniasis, Cutaneous parasitology transmission MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Parasites genetics MeSH
- Psychodidae parasitology MeSH
- Whole Genome Sequencing MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Israel MeSH