Lineage-specific positive selection at the merozoite surface protein 1 (msp1) locus of Plasmodium vivax and related simian malaria parasites

<p>Abstract</p> <p>Background</p> <p>The 200 kDa merozoite surface protein 1 (MSP-1) of malaria parasites, a strong vaccine candidate, plays a key role during erythrocyte invasion and is a target of host protective immune response. <it>Plasmodium vivax</it>, the most widespread human malaria parasite, is closely related to parasites that infect Asian Old World monkeys, and has been considered to have become a parasite of man by host switch from a macaque malaria parasite. Several Asian monkey parasites have a range of natural hosts. The same parasite species shows different disease manifestations among host species. This suggests that host immune responses to <it>P. vivax</it>-related malaria parasites greatly differ among host species (albeit other factors). It is thus tempting to invoke that a major immune target parasite protein such as MSP-1 underwent unique evolution, depending on parasite species that exhibit difference in host range and host specificity.</p> <p>Results</p> <p>We performed comparative phylogenetic and population genetic analyses of the gene encoding MSP-1 (<it>msp1</it>) from <it>P. vivax </it>and nine <it>P. vivax</it>-related simian malaria parasites. The inferred phylogenetic tree of <it>msp1 </it>significantly differed from that of the mitochondrial genome, with a striking displacement of <it>P. vivax </it>from a position close to <it>P. cynomolgi </it>in the mitochondrial genome tree to an outlier of Asian monkey parasites. Importantly, positive selection was inferred for two ancestral branches, one leading to <it>P. inui </it>and <it>P. hylobati </it>and the other leading to <it>P. vivax</it>, <it>P. fieldi </it>and <it>P. cynomolgi</it>. This ancestral positive selection was estimated to have occurred three to six million years ago, coinciding with the period of radiation of Asian macaques. Comparisons of <it>msp1 </it>polymorphisms between <it>P. vivax</it>, <it>P. inui </it>and <it>P. cynomolgi </it>revealed that while some positively selected amino acid sites or regions are shared by these parasites, amino acid changes greatly differ, suggesting that diversifying selection is acting species-specifically on <it>msp1</it>.</p> <p>Conclusions</p> <p>The present results indicate that the <it>msp1 </it>locus of <it>P. vivax </it>and related parasite species has lineage-specific unique evolutionary history with positive selection. <it>P. vivax </it>and related simian malaria parasites offer an interesting system toward understanding host species-dependent adaptive evolution of immune-target surface antigen genes such as <it>msp1</it>.</p

Paramyxovirus Diversity within One Population of Miniopterus fuliginosus Bats in Sri Lanka

Bats are known as typical reservoirs for a number of viruses, including viruses of the family Paramyxoviridae. Representatives of the subfamily Orthoparamyxovirinae are distributed worldwide and can cause mild to fatal diseases when infecting humans. The research on Paramyxoviruses (PMVs) from different bat hosts all over the world aims to understand the diversity, evolution and distribution of these viruses and to assess their zoonotic potential. A high number of yet unclassified PMVs from bats are recorded. In our study, we investigated bat species from the families Rhinolophidae, Hipposiderae, Pteropodidae and Miniopteridae that are roosting sympatrically in the Wavul Galge cave (Koslanda, Sri Lanka). The sampling at three time points (March and July 2018; January 2019) and screening for PMVs with a generic PCR show the presence of different novel PMVs in 10 urine samples collected from Miniopterus fuliginosus. Sequence analysis revealed a high similarity of the novel strains among each other and to other unclassified PMVs collected from Miniopterus bats. In this study, we present the first detection of PMVs in Sri Lanka and the presence of PMVs in the bat species M. fuliginosus for the first time.Peer Reviewe

Full Genome of batCoV/MinFul/2018/SriLanka, a Novel Alpha-Coronavirus Detected in Miniopterus fuliginosus, Sri Lanka

Coronaviruses (CoV) are divided into the genera α-CoVs, β-CoVs, γ-CoVs and δ-CoVs. Of these, α-CoVs and β-CoVs are solely capable of causing infections in humans, resulting in mild to severe respiratory symptoms. Bats have been identified as natural reservoir hosts for CoVs belonging to these two genera. Consequently, research on bat populations, CoV prevalence in bats and genetic characterization of bat CoVs is of special interest to investigate the potential transmission risks. We present the genome sequence of a novel α-CoV strain detected in rectal swab samples of Miniopterus fuliginosus bats from a colony in the Wavul Galge cave (Koslanda, Sri Lanka). The novel strain is highly similar to Miniopterus bat coronavirus 1, an α-CoV located in the subgenus of Minunacoviruses. Phylogenetic reconstruction revealed a high identity of the novel strain to other α-CoVs derived from Miniopterus bats, while human-pathogenic α-CoV strains like HCoV-229E and HCoV-NL63 were more distantly related. Comparison with selected bat-related and human-pathogenic strains of the β-CoV genus showed low identities of ~40%. Analyses of the different genes on nucleotide and amino acid level revealed that the non-structural ORF1a/1b are more conserved among α-CoVs and β-CoVs, while there are higher variations in the structural proteins known to be important for host specificity. The novel strain was named batCoV/MinFul/2018/SriLanka and had a prevalence of 50% (66/130) in rectal swab samples and 58% (61/104) in feces samples that were collected from Miniopterus bats in Wavul Galge cave. Based on the differences between strain batCoV/MinFul/2018/SriLanka and human-pathogenic α-CoVs and β-CoVs, we conclude that there is a rather low transmission risk to humans. Further studies in the Wavul Galge cave and at other locations in Sri Lanka will give more detailed information about the prevalence of this virus.Peer Reviewe

Strain-specific protective effect of the immunity induced by live malarial sporozoites under chloroquine cover.

The efficacy of a whole-sporozoite malaria vaccine would partly be determined by the strain-specificity of the protective responses against malarial sporozoites and liver-stage parasites. Evidence from previous reports were inconsistent, where some studies have shown that the protective immunity induced by irradiated or live sporozoites in rodents or humans were cross-protective and in others strain-specific. In the present work, we have studied the strain-specificity of live sporozoite-induced immunity using two genetically and immunologically different strains of Plasmodium cynomolgi, Pc746 and PcCeylon, in toque monkeys. Two groups of monkeys were immunized against live sporozoites of either the Pc746 (n = 5), or the PcCeylon (n = 4) strain, by the bites of 2-4 sporozoite-infected Anopheles tessellates mosquitoes per monkey under concurrent treatments with chloroquine and primaquine to abrogate detectable blood infections. Subsequently, a group of non-immunized monkeys (n = 4), and the two groups of immunized monkeys were challenged with a mixture of sporozoites of the two strains by the bites of 2-5 infective mosquitoes from each strain per monkey. In order to determine the strain-specificity of the protective immunity, the proportions of parasites of the two strains in the challenge infections were quantified using an allele quantification assay, Pyrosequencing™, based on a single nucleotide polymorphism (SNP) in the parasites' circumsporozoite protein gene. The Pyrosequencing™ data showed that a significant reduction of parasites of the immunizing strain in each group of strain-specifically immunized monkeys had occurred, indicating a stronger killing effect on parasites of the immunizing strain. Thus, the protective immunity developed following a single, live sporozoite/chloroquine immunization, acted specifically against the immunizing strain and was, therefore, strain-specific. As our experiment does not allow us to determine the parasite stage at which the strain-specific protective immunity is directed, it is possible that the target of this immunity could be either the pre-erythrocytic stage, or the blood-stage, or both

Topical Anti-Inflammatory Activity of Essential Oils of Alpinia calcarata Rosc., Its Main Constituents, and Possible Mechanism of Action

This study aimed at investigating the anti-inflammatory potential of essential oil from rhizome and leaf of Alpinia calcarata Rosc. (ACEO) with the focus of its topical anti-inflammatory activity along with its dominant compounds 1,8-cineole and α-terpineol using mouse ear edema model. ACEOs were analyzed by GC-MS. The anti-inflammatory activity was determined by studying the inhibition of overproduction of proinflammatory mediators—nitric oxide, reactive oxygen species, prostaglandins, cyclooxygenases, and cytokines induced by lipopolysaccharides in murine macrophages. Topical anti-inflammatory and antinociceptive activity was studied by 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin inflammation and formalin-induced pain model in mice, respectively. Rhizome oil has 1,8-cineole (31.08%), α-terpineol (10.31%), and fenchyl acetate (10.73%) as major compounds whereas the ACEO from leaves has 1,8-cineole (38.45%), a-terpineol (11.62%), and camphor (10%). ACEOs reduced the production of inflammatory mediators in vitro in a concentration-dependent manner. Further, ACEO and its major compounds reduced ear thickness, weight, myeloperoxidase, and cytokines significantly (p<0.01) in mouse ear. Dose-dependent reduction in flinching and licking in both the phases of pain sensation concludes the topical analgesic effect. Our findings suggest the potency of topical use of ACEOs for inflammatory disease conditions

MOESM1 of Synthesis and characterization of novel rhenium(I) complexes towards potential biological imaging applications

Additional file 1: Table S1. 1H NMR chemical shifts (ppm) of complexes 1–4 in D2O at 25 °C. 1H NMR chemical shifts (ppm) of complexes 1–4 in D2O at 25 °C. Figure S1. UV VIS spectra of L1 (top), Re(CO)3L1Br (2, middle) and [Re(CO)3L1(H2O)]+ (1, bottom). Figure S2. UV VIS spectra of L2 (top), [Re(CO)3L2(H2O)]+ (3, middle) and Re(CO)3L2Br (4, bottom). Figure S3. 1H-13C HSQC spectrum of a selected region of [Re(CO)3L1(H2O)]OTf (1) (25 °C, D2O, shifts in ppm). Figure S4. 1H-1H ROESY spectrum of a selected region of [Re(CO)3L1(H2O)]OTf (1) (25 °C, D2O, shifts in ppm). Figure S5. 1H-13C HSQC spectrum of a selected region of [Re(CO)3L2(H2O)]OTf (3) (25 °C, D2O, shifts in ppm). Figure S6. 1H-1H ROESY spectrum of a selected region of [Re(CO)3L2(H2O)]OTf (3) (25 °C, D2O, shifts in ppm)