Analysis of Hepatitis B Virus Genotype D in Greenland Suggests the Presence of a Novel Quasi-Subgenotype

A disproportionate number of Greenland's Inuit population are chronically infected with Hepatitis B virus (HBV; 5-10%). HBV genotypes B and D are most prevalent in the circumpolar Arctic. Here, we report 39 novel HBV/D sequences from individuals residing in southwestern Greenland. We performed phylodynamic analyses with ancient HBV DNA calibrators to investigate the origin and relationship of these taxa to other HBV sequences. We inferred a substitution rate of 1.4 × 10-5 [95% HPD 8.8 × 10-6, 2.0 × 10-5] and a time to the most recent common ancestor of 629 CE [95% HPD 37-1138 CE]. The Greenland taxa form a sister clade to HBV/D2 sequences, specifically New Caledonian and Indigenous Taiwanese sequences. The Greenland sequences share amino acid signatures with subgenotypes D1 and D2 and ~97% sequence identity. Our results suggest the classification of these novel sequences does not fit within the current nomenclature. Thus, we propose these taxa be considered a novel quasi-subgenotype

Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome

The ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain–Barré syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of “TORCH” viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication

Zika Virus: Medical Countermeasure Development Challenges

Introduction: Reports of high rates of primary microcephaly and Guillain–Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment. Methods: Multiple information sources were employed to support the review. These included publically available literature, patents, official communications, English and Lusophone lay press. Online surveys were distributed to physicians in the US, Mexico and Argentina and responses analyzed. Computational epitope analysis as well as infectious disease outbreak modeling and forecasting were implemented. Field observations in Brazil were compiled and interviews conducted with public health officials

Identification of candidate genes for aluminum tolerance in hexaploid oat

Solos ácidos causam redução do rendimento de plantas de lavoura, tanto pela redução da disponibilidade de nutrientes como pela presença de elementos tóxicos, como o alumínio (Al) na sua forma mais reativa. A combinação entre estes dois fatores tem consequências graves para a planta, tais como a redução do crescimento de raízes e da produção de biomassa. A aveia possui tolerância ao Al quando comparada com trigo e cevada, porém há considerável variação dentro da espécie. Os mecanismos de tolerância ao Al em aveia ainda não foram elucidados. Na família Poaceae, tanto mecanismos de exclusão quanto de detoxificação foram identificados, e vários genes associados à tolerância ao Al. Os objetivos deste trabalho foram: identificar QTLs associados à tolerância ao Al a partir da fenotipagem a campo e em hidroponia de uma população segregante e sequências com homologia a genes associados a tolerância ao Al em outras espécies. Foi gerado um mapa genético para a população oriunda do cruzamento de UFRGS17 e UFRGS930598, aonde foram encontrados três QTLs associados à tolerância ao Al em hidroponia, explicando 64% da variação fenotípica. Não foram identificados QTLs para tolerância ao Al a campo. Sequência homóloga ao gene ALMT1 foi identificada, sendo predita a existência de cinco íntrons e seis exons e uma proteína com seis domínios transmembrana no alelo identificado em UFRGS 17. Em UFRGS 930598, o primeiro exon e parte do primeiro intron não foram obtidos. Também foi identificado parcialmente uma sequência homóloga ao gene STOP1 com 89% de similaridade a sequência de Brachypodium distachyon.Acid soils reduce crop yield, not only by affecting nutrient availability, but also by increasing the presence of toxic element forms, such as aluminum (Al), in its most reactive form. The combination of these two factors has negative consequences to the plant, for example reduction in root growth and biomass production. Oats are considered Al tolerant if compared to wheat and barley, but there is a large variation inside the species. In poaceae, mechanisms related to exclusion as weel as to detoxification have been identified and several genes have been associated to Al tolerance.This study aimed to identify QTLs associated to Al tolerance using field and hydroponic phenotyping of a recombinant inbred population, and identify sequences with homology to genes associated to Al tolerance in other species. Three QTLs associated to hydroponic Al tolerance were identified in the map generated to UFRGS 17 x UFRGS 930598 population, explaining 64% of the phenotypic variation. A sequence similar to the ALMT1 gene was identified. The UFRGS 17 alIele was predicted to contain five introns and six exons and to code a protein with six transmembrane domains. In UFRGS 930598, the first predicted exon and part of the first intron were not cloned. A sequence similar to the STOP1 gene was partially identified with 89 % of homology to the Brachypodium distachyon homologous sequence

Identification of candidate genes for aluminum tolerance in hexaploid oat

Solos ácidos causam redução do rendimento de plantas de lavoura, tanto pela redução da disponibilidade de nutrientes como pela presença de elementos tóxicos, como o alumínio (Al) na sua forma mais reativa. A combinação entre estes dois fatores tem consequências graves para a planta, tais como a redução do crescimento de raízes e da produção de biomassa. A aveia possui tolerância ao Al quando comparada com trigo e cevada, porém há considerável variação dentro da espécie. Os mecanismos de tolerância ao Al em aveia ainda não foram elucidados. Na família Poaceae, tanto mecanismos de exclusão quanto de detoxificação foram identificados, e vários genes associados à tolerância ao Al. Os objetivos deste trabalho foram: identificar QTLs associados à tolerância ao Al a partir da fenotipagem a campo e em hidroponia de uma população segregante e sequências com homologia a genes associados a tolerância ao Al em outras espécies. Foi gerado um mapa genético para a população oriunda do cruzamento de UFRGS17 e UFRGS930598, aonde foram encontrados três QTLs associados à tolerância ao Al em hidroponia, explicando 64% da variação fenotípica. Não foram identificados QTLs para tolerância ao Al a campo. Sequência homóloga ao gene ALMT1 foi identificada, sendo predita a existência de cinco íntrons e seis exons e uma proteína com seis domínios transmembrana no alelo identificado em UFRGS 17. Em UFRGS 930598, o primeiro exon e parte do primeiro intron não foram obtidos. Também foi identificado parcialmente uma sequência homóloga ao gene STOP1 com 89% de similaridade a sequência de Brachypodium distachyon.Acid soils reduce crop yield, not only by affecting nutrient availability, but also by increasing the presence of toxic element forms, such as aluminum (Al), in its most reactive form. The combination of these two factors has negative consequences to the plant, for example reduction in root growth and biomass production. Oats are considered Al tolerant if compared to wheat and barley, but there is a large variation inside the species. In poaceae, mechanisms related to exclusion as weel as to detoxification have been identified and several genes have been associated to Al tolerance.This study aimed to identify QTLs associated to Al tolerance using field and hydroponic phenotyping of a recombinant inbred population, and identify sequences with homology to genes associated to Al tolerance in other species. Three QTLs associated to hydroponic Al tolerance were identified in the map generated to UFRGS 17 x UFRGS 930598 population, explaining 64% of the phenotypic variation. A sequence similar to the ALMT1 gene was identified. The UFRGS 17 alIele was predicted to contain five introns and six exons and to code a protein with six transmembrane domains. In UFRGS 930598, the first predicted exon and part of the first intron were not cloned. A sequence similar to the STOP1 gene was partially identified with 89 % of homology to the Brachypodium distachyon homologous sequence

Arboviruses: The Hidden Path of an Imminent Threat

Arboviruses are a grade of viruses carried by arthropods, which have been in the headlines due to recent epidemics. Members of this grade are the families Flaviviridae which includes Zika (ZIKV), Dengue (DENV), Yellow Fever (YFV), among other viruses and Togaviridae, which includes Chikungunya (CHIKV). Research on some arboviruses has been strong over the past couple of decades. Other arboviruses have not garnered much attention until lately. For example, ZIKV has been understudied until 2015. Since the 1950s ZIKV was considered to cause only a benign infection in humans. ZIKV became well studied only after the recent outbreaks of the virus in the Pacific, Americas, and South-East Asia, was found to be related to severe neuropathology, which includes the development of neurological defects such as microcephaly on the fetus and Guillain Barré Syndrome in adults. CHIKV is another arbovirus that although been circulating for a long time in Africa and Asia, has been recently introduced into the Americas in 2013, causing recurring outbreaks in South and Central American naïve populations. YFV, which been known to be endemic and thought to be controlled in South America, has re-emerged in Brazil beginning in December 2016. This outbreak, although restricted to transmission by the sylvatic mosquito Haemagogus leococelaenus, raised questions among researchers regarding the potential for spread to the United States due to the presence of the urban vectors Aedes aegypti and Aedes albopictus} and a naïve, largely unvaccinated population. Another question that still remains is whether YFV will ever reach the Asian continent? Today, the time it takes for awareness of the health organizations, to convince the funding agencies, and to work on vaccine development is much more than the time needed for the disease to change from a local outbreak to a global epidemic. The overall objective of this work is to provide the grounds for a viral surveillance system based on evolution, utilizing the current ZIKV and CHIKV outbreaks and other arboviruses as case studies. Utilizing phylogenetic and molecular sequence alignment tools I developed a pipeline to evaluate the genomic changes of viruses on CHIKV and ZIKV. I also created a pipeline to generate pathogen transmission networks and compare different disease networks utilizing different network centrality metrics. CHIKV, DENV, YFV and ZIKV were utilized as case studies. The strategies utilized in this work will enable better abatement and management strategies of viral outbreaks. My findings indicate that changes in the coding sequence does not seem to be the main reason why ZIKV has changed its behavior in terms of pathogenicity. In CHIKV there is an insertion on the UTR region of a group of sequences and change of virulence has been associated with UTR sizes in different CHIKV strains. Upon analyzing viral 3' and 5' UTRs, a trinuncleotide motif, known as Musashi Binding Element was identified in both CHIKV and ZIKV, its presence and availability on ZIKV may explain a preference to human cells, in CHIKV the motif is present but not available. Although both CHIKV and ZIKV coexist and have spread in the same regions in a short period of time, their spread seems to be from independent events. When looking at transmission networks, there is a high correlation between the different centrality metrics utilized to measure all four DENV serotypes transmission networks, CHIKV, YFV and ZIKV have lower correlation, thus, distinct patterns