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Genetics and Genomics of Vector-Borne Disease Pathogens

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (30 July 2023) | Viewed by 7966

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Special Issue Editor

Prof. Dr. Eugenia Lo

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Guest Editor

Biological Sciences, University of North Carolina Charlotte, Charlotte, NC 28262, USA
Interests: malaria parasites; spatial epidemiology; host-pathogen interactions; invasion mechanism; population genomics; transcriptomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes. In 2018, the World Health Organization estimated 3.4 billion people were at risk of malaria with approximately 93% of malaria cases and 94% of deaths occurring in sub-Saharan Africa. In non-human primates, approximately 25 malaria parasite species have been described (Faust and Dobson 2015, One Health 1:66-75). Among them, six species including Plasmodium falciparum, P. vivax. P. malariae, P. ovale, P. knowlesi and P. simium are known to infect humans, causing symptoms. Plasmodium falciparum is responsible for hundreds of millions of cases of malaria and kills about half a million annually. While P. falciparum causes most malaria mortality, P. vivax can also cause severe disease in South America and South East Asia. Recently, there has also been a surge of P. vivax in sub-Saharan Africa.

Knowledge around the genetics and genomics of malaria parasites can uncover inheritance patterns and mutational changes of infectious pathogens, molecular mechanisms underlying red blood cell invasion, as well as effectiveness of malaria interventions over time. The advent and accessibility of high-throughput sequencing technologies and bioinformatic tools in the last decade provides remarkable insights into the global genetic structure, genomic composition and recombination rates, as well as genetic variants associated with antimalarial drug resistance of Plasmodium. Global malaria elimination programs focus primarily on P. falciparum. Nevertheless, non-P. falciparum malaria still presents a major challenge for malaria elimination. Recent research efforts and control programs have drawn resources to P. vivax malaria. By contrast, other Plasmodium species receive little attention, and malaria caused by these organisms is among the most neglected tropical diseases.

This Special Issue will cover the genetic and/or genomic features of the various malaria parasite species in the context of disease epidemiology, evolution, functions of genes or gene products, and host–pathogen interactions. We cordially invite researchers working in these areas to contribute to this Special Issue with original research or reviews.

Prof. Eugenia Lo
Dr. Karthigayan Gunalan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

functional genomics
epigenetics
molecular parasitology
cell biology
antimalarial resistance
antigenic variations
gene functions and products
host–pathogen interactions
malaria interventions

Published Papers (4 papers)

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13 pages, 2699 KiB

Open AccessArticle

Dates and Rates of Tick-Borne Encephalitis Virus—The Slowest Changing Tick-Borne Flavivirus

by Artem N. Bondaryuk, Nina V. Kulakova, Olga I. Belykh and Yurij S. Bukin

Int. J. Mol. Sci. 2023, 24(3), 2921; https://doi.org/10.3390/ijms24032921 - 02 Feb 2023

Cited by 5 | Viewed by 1797

Abstract

We evaluated the temporal signal and substitution rate of tick-borne encephalitis virus (TBEV) using 276 complete open reading frame (ORF) sequences with known collection dates. According to a permutation test, the TBEV Siberian subtype (TBEV-S) data set has no temporal structure and cannot be applied for substitution rate estimation without other TBEV subtypes. The substitution rate obtained suggests that the common clade of TBEV (TBEV-common), including all TBEV subtypes and louping-ill virus (LIV), is characterized by the lowest rate (1.87 × 10⁻⁵ substitutions per site per year (s/s/y) or 1 nucleotide substitution per ORF per 4.9 years; 95% highest posterior density (HPD) interval, 1.3–2.4 × 10⁻⁵ s/s/y) among all tick-borne flaviviruses previously assessed. Within TBEV-common, the TBEV European subtype (TBEV-E) has the lowest substitution rate (1.3 × 10⁻⁵ s/s/y or 1 nucleotide substitution per ORF per 7.5 years; 95% HPD, 1.0–1.8 × 10⁻⁵ s/s/y) as compared with TBEV Far-Eastern subtype (3.0 × 10⁻⁵ s/s/y or 1 nucleotide substitution per ORF per 3.2 years; 95% HPD, 1.6–4.5 × 10⁻⁵ s/s/y). TBEV-common representing the species tick-borne encephalitis virus diverged 9623 years ago (95% HPD interval, 6373–13,208 years). The TBEV Baikalian subtype is the youngest one (489 years; 95% HPD, 291–697 years) which differs significantly by age from TBEV-E (848 years; 95% HPD, 596–1112 years), LIV (2424 years; 95% HPD, 1572–3400 years), TBEV-FE (1936 years, 95% HPD, 1344–2598 years), and the joint clade of TBEV-S (2505 years, 95% HPD, 1700–3421 years) comprising Vasilchenko, Zausaev, and Baltic lineages. Full article

(This article belongs to the Special Issue Genetics and Genomics of Vector-Borne Disease Pathogens)

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17 pages, 1983 KiB

Open AccessArticle

Genomic Determinants Potentially Associated with Clinical Manifestations of Human-Pathogenic Tick-Borne Flaviviruses

by Artem N. Bondaryuk, Nina V. Kulakova, Ulyana V. Potapova, Olga I. Belykh, Anzhelika V. Yudinceva and Yurij S. Bukin

Int. J. Mol. Sci. 2022, 23(21), 13404; https://doi.org/10.3390/ijms232113404 - 02 Nov 2022

Cited by 1 | Viewed by 1730

Abstract

The tick-borne flavivirus group contains at least five species that are pathogenic to humans, three of which induce encephalitis (tick-borne encephalitis virus, louping-ill virus, Powassan virus) and another two species induce hemorrhagic fever (Omsk hemorrhagic fever virus, Kyasanur Forest disease virus). To date, the molecular mechanisms responsible for these strikingly different clinical forms are not completely understood. Using a bioinformatic approach, we performed the analysis of each amino acid (aa) position in the alignment of 323 polyprotein sequences to calculate the fixation index (F_st) per site and find the regions (determinants) where sequences belonging to two designated groups were most different. Our algorithm revealed 36 potential determinants (F_st ranges from 0.91 to 1.0) located in all viral proteins except a capsid protein. In an envelope (E) protein, most of the determinants were located on the virion surface regions (domains II and III) and one (absolutely specific site 457) was located in the transmembrane region. Another 100% specific determinant site (E63D) with F_st = 1.0 was located in the central hydrophilic domain of the NS2b, which mediates NS3 protease activity. The NS5 protein contains the largest number of determinants (14) and two of them are absolutely specific (T226S, E290D) and are located near the RNA binding site 219 (methyltransferase domain) and the extension structure. We assume that even if not absolutely, highly specific sites, together with absolutely specific ones (F_st = 1.0) can play a supporting role in cell and tissue tropism determination. Full article

(This article belongs to the Special Issue Genetics and Genomics of Vector-Borne Disease Pathogens)

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12 pages, 2070 KiB

Open AccessArticle

Sensing the Messenger: Potential Roles of Cyclic-di-GMP in Rickettsial Pathogenesis

by Hema P. Narra, Abha Sahni, Krishna Mohan Sepuru, Jessica Alsing and Sanjeev K. Sahni

Int. J. Mol. Sci. 2022, 23(7), 3853; https://doi.org/10.3390/ijms23073853 - 31 Mar 2022

Cited by 1 | Viewed by 1516

Abstract

Pathogenic bacteria causing human rickettsioses, transmitted in nature by arthropod vectors, primarily infect vascular endothelial cells lining the blood vessels, resulting in ‘endothelial activation’ and onset of innate immune responses. Nucleotide second messengers are long presumed to be the stimulators of type I interferons, of which bacterial cyclic-di-GMP (c-di-GMP) has been implicated in multiple signaling pathways governing communication with other bacteria and host cells, yet its importance in the context of rickettsial interactions with the host has not been investigated. Here, we report that all rickettsial genomes encode a putative diguanylate cyclase pleD, responsible for the synthesis of c-di-GMP. In silico analysis suggests that although the domain architecture of PleD is apparently well-conserved among different rickettsiae, the protein composition and sequences likely vary. Interestingly, cloning and sequencing of the pleD gene from virulent (Sheila Smith) and avirulent (Iowa) strains of R. rickettsii reveals a nonsynonymous substitution, resulting in an amino acid change (methionine to isoleucine) at position 236. Additionally, a previously reported 5-bp insertion in the genomic sequence coding for pleD (NCBI accession: NC_009882) was not present in the sequence of our cloned pleD from R. rickettsii strain Sheila Smith. In vitro infection of HMECs with R. rickettsii (Sheila Smith), but not R. rickettsii (Iowa), resulted in dynamic changes in the levels of pleD up to 24 h post-infection. These findings thus provide the first evidence for the potentially important role(s) of c-di-GMP in the determination of host-cell responses to pathogenic rickettsiae. Further studies into molecular mechanisms through which rickettsial c-di-GMP might regulate pathogen virulence and host responses should uncover the contributions of this versatile bacterial second messenger in disease pathogenesis and immunity to human rickettsioses. Full article

(This article belongs to the Special Issue Genetics and Genomics of Vector-Borne Disease Pathogens)

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Other

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6 pages, 1903 KiB

Open AccessCase Report

Tick-Borne Encephalitis Virus RNA Found in Frozen Goat’s Milk in a Family Outbreak

by Eirini Mylonaki, Michael Seiberl, Neil Jones, Heike Bernhard, Ferdinand Otto, Georg Pilz, Eugen Trinka and Peter Wipfler

Int. J. Mol. Sci. 2022, 23(19), 11632; https://doi.org/10.3390/ijms231911632 - 01 Oct 2022

Cited by 3 | Viewed by 1737

Abstract

Tick-borne encephalitis (TBE) is one of the commonest arthropod-borne viral diseases in Middle-East Europe and North Asia. The main reservoir of the virus is comprised of small rodents and domestic mammals with the common tick (Ixodes) being the usual vector. The clinical spectrum of TBE ranges from mild meningitis to severe meningoencephalomyelitis. This disease can lead to severe sequelae and has a mortality up to 2% in Europe. Even though the majority of cases are transmitted through bites of infected ticks, infections through ingestion of contaminated milk and dairy products from farms in endemic areas have been reported. We report a family outbreak of a febrile disease, initially suggestive of human-to-human infection, during the early summertime in Austria. Tick-borne encephalitis was diagnosed following consumption of unpasteurised goat’s milk and the virus was subsequently detected in frozen milk samples. Although this is a rare manifestation of TBE, this case series shows that TBE should be included in the differential diagnosis of an outbreak of febrile disease, and a careful clinical history with reference to unpasteurized dairy products is crucial in order to prevent further disease spread. The best preventive measure is active immunisation of people living in, or travelling to, endemic areas. Full article

(This article belongs to the Special Issue Genetics and Genomics of Vector-Borne Disease Pathogens)

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