Virulence factor RNA transcript expression in the Leishmania Viannia subgenus: influence of species, isolate source, and Leishmania RNA virus-1

Kariyawasam, Ruwandi; Mukkala, Avinash N.; Lau, Rachel; Valencia, Braulio M.; Llanos-Cuentas, Alejandro; Boggild, Andrea K.

doi:10.1186/s41182-019-0153-x

Cited by 19 publications

(41 citation statements)

References 43 publications

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“…Since L. infantum-induced visceral form, (the most invasive leishmaniasis) and L. major induce a more devastating form of CL compared to L. tropica, the higher level of CPB expression is expected in these species. Moreover, in agreement with our findings, a study by Kariyawasam et al [27] revealed that pooled virulence factors transcript was lower in L. (V.) panamensis isolates than that of L.(V.) braziliensis and L. (V.) guyananesis at 24 h post macrophage infection, which might reflect that a strain of L. (V.) panamensis originated from a patient with non-severe CL while L. (V.) braziliensis isolates derived from more clinically invasive lesions. These findings suggested the most expression of virulence factors could be exhibited in the species inducing more severe clinical forms [27,28].…”

Section: Discussionsupporting

confidence: 94%

“…In this context, a correlation between the CPB expression and virulence has been reported in L. amazonensis promastigotes [29]. Also, the highest expression of CPB was reported in L. (V.) braziliensis isolates derived from more clinically invasive lesions in comparison with a strain of L. (V.) panamensis originated from a patient with non-severe CL, suggesting an association of clinical phenotype and expression level of virulence factors [27]. Likewise, our findings suggest a probable correlation between the duration of wound and CPB gene expression; however, since the progression of wound is multifactorial further analysis is needed to confirm it.…”

Section: Discussionmentioning

confidence: 90%

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Comparison of Cysteine Protease B Gene Expression between Clinical Isolates of Leishmania tropica, Leishmania major and Leishmania infantum

Kazemirad

Nafchi

Latifi

et al. 2019

JoMMID

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Introduction: Leishmania cysteine protease B (CPB) is a parasite virulence factor that plays a vital role in host-parasitic interactions. Regarding the importance of the CPB gene, we used a quantitative real-time RT-PCR to investigate the expression of CPB in the Iranian isolates of different Leishmania species. Methods: In this study, 36 clinical samples were collected, out of which 29 belonged to cutaneous leishmaniasis (CL), 3 to viscerotropic leishmaniasis (VTL), and 5 to visceral leishmaniasis (VL) patients. Among CL isolates, 8 were Leishmania major, and 21 were Leishmania tropica, including 3 isolates from the lupoid type. After RNA extraction and cDNA synthesis, gene expression analysis was performed by qPCR. Results: Our results showed the highest expression of CPB in isolates of Leishmania infantum, followed by L. major and L. tropica. Among L. tropica isolates, in the lupoid forms, the mean expression of CPB was ≈6.4 times higher than that of non-lupoid isolates. In L. major isolates, a significant difference was observed between the level of gene expression and the duration of the infection. The expression level of CPB was associated with the severity of the infection in L. infantum isolates. Conclusion: The CPB gene expressed in all Leishmania species. The highest expression was in L. infantum species and the least expression in L. tropica. The transcript level of CPB increased in L. major isolates derived from patients with a higher number and duration of ulcers; however, further studies on more clinical samples are needed to explore our findings.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 90%

Comparison of Cysteine Protease B Gene Expression between Clinical Isolates of Leishmania tropica, Leishmania major and Leishmania infantum

Kazemirad

Nafchi

Latifi

et al. 2019

JoMMID

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“…equipped with RNA interference machinery (the system allowing the cell to actively recognize and degrade non-self dsRNA, likely to be mainly of viral origin) suggesting the importance of the parasite’s anti-viral defense in finely balancing viral replication rate [ 87 ]. Differently from TVV, the presence of LRV does not affect parasite growth and there is no evidence of modulation of parasite gene expression [ 88 ]. Despite LRV has been isolated from active and healing lesions and scars [ 89 – 91 ], thus far no experimental system has allowed long-term maintenance of LRV in Leishmania following experimental transfer (N. Fasel personal communication).…”

Section: Main Textmentioning

confidence: 99%

Viruses of protozoan parasites and viral therapy: Is the time now right?

Barrow

Dujardin

Fasel

et al. 2020

Virol J

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Infections caused by protozoan parasites burden the world with huge costs in terms of human and animal health. Most parasitic diseases caused by protozoans are neglected, particularly those associated with poverty and tropical countries, but the paucity of drug treatments and vaccines combined with increasing problems of drug resistance are becoming major concerns for their control and eradication. In this climate, the discovery/repurposing of new drugs and increasing effort in vaccine development should be supplemented with an exploration of new alternative/synergic treatment strategies. Viruses, either native or engineered, have been employed successfully as highly effective and selective therapeutic approaches to treat cancer (oncolytic viruses) and antibiotic-resistant bacterial diseases (phage therapy). Increasing evidence is accumulating that many protozoan, but also helminth, parasites harbour a range of different classes of viruses that are mostly absent from humans. Although some of these viruses appear to have no effect on their parasite hosts, others either have a clear direct negative impact on the parasite or may, in fact, contribute to the virulence of parasites for humans. This review will focus mainly on the viruses identified in protozoan parasites that are of medical importance. Inspired and informed by the experience gained from the application of oncolytic virus- and phage-therapy, rationally-driven strategies to employ these viruses successfully against parasitic diseases will be presented and discussed in the light of the current knowledge of the virus biology and the complex interplay between the viruses, the parasite hosts and the human host. We also highlight knowledge gaps that should be addressed to advance the potential of virotherapy against parasitic diseases.

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“…Virulence factors are considered potential drug targets and vaccine candidates for controlling leishmaniasis [12]. Cysteine proteinases (CPs) are immunogenic proteins and include cysteine protease types I-III (CPB, CPA, and CPC, respectively).…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity and potential protection of DNA vaccine of Leishmania martiniquensis against Leishmania infection in mice

Aunguldee

Gerdprasert

Tangteerawatana

et al. 2021

J Infect Dev Ctries

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Introduction: In Thailand, Leishmania martiniquensis is the predominant species causing cutaneous and visceral leishmaniasis. Its incidence has been increasing among immunocompetent and immunocompromised hosts. We developed a prototype DNA vaccine using a partial consensus sequence of the cysteine protease B (cpb) gene derived from L. martiniquensis from Thai patients. Methodology: The laboratory inbred strain of albino BALB/c mice were immunized intramuscularly three times at 2-week intervals (weeks 0, 2, and 4) with cpb plasmid DNA (pcDNA_cpb) with or without the adjuvant, monoolein (pcDNA_cpb-MO). Mice were challenged at week 6 with L. martiniquensis promastigotes. Sera were analysed for IgG1, IgG2a, interferon gamma and interleukin 10 (IFN-γ and IL-10, respectively) levels at weeks 0, 4, and 9. Additionally, livers and spleens were also analysed for parasite burden using immunohistochemistry and real-time polymerase chain (qPCR) assays. Results: Three weeks after promastigote challenge, vaccinated mice showed significantly increased levels of IgG2a and IFN-γ while IL-10 level was significantly reduced when compared with those in the control group (p < 0.01). Parasite burden in the livers and spleens of vaccinated mice significantly decreased. In addition, a significant increase in mature granuloma formation in the livers when compared with those of the control group (p < 0.05) was found, indicating increased T-helper cells (Th1)-induced inflammation and destruction of amastigotes. Monoolein produced a booster effect to enhance the mouse Th1 protective immunity. Conclusions: The prototype DNA vaccine could induce a Th1 immune response that conferred potential protection to the L. martiniquensis promastigote challenge in BALB/c mice.

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Virulence factor RNA transcript expression in the Leishmania Viannia subgenus: influence of species, isolate source, and Leishmania RNA virus-1

Cited by 19 publications

References 43 publications

Comparison of Cysteine Protease B Gene Expression between Clinical Isolates of Leishmania tropica, Leishmania major and Leishmania infantum

Comparison of Cysteine Protease B Gene Expression between Clinical Isolates of Leishmania tropica, Leishmania major and Leishmania infantum

Viruses of protozoan parasites and viral therapy: Is the time now right?

Immunogenicity and potential protection of DNA vaccine of Leishmania martiniquensis against Leishmania infection in mice

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