RESUMO
Rotaviruses (RVs) are the most common etiological agent of acute gastroenteritis among young children, even after vaccine introduction in low-income countries. A whole-genome classification representing the 11 RV genes, was introduced for surveillance and characterization of RVs. This study characterized the common circulating strains in Vellore, India from 2002 to 2017 to understand rotavirus strain diversity and evolution using Whole genome sequencing (WGS) carried out on Illumina MiSeq. The 89% (92% of Wa-like, 86% of DS-1-like) of strains had classical constellations, while reassortant constellations were seen in 11% (8% of Wa-like, 14% of DS-1-like) of the strains. The rare E6-NSP4 in combination with DS-1 like G1P[8] and the emergence of the OP-354 subtype of P[8] were identified. Phylogenetics of RV strains revealed multiple subtypes circulating in the past 15 years, with strong evidence of animal to human gene transmission among several strains.
RESUMO
Hantaviruses are the etiological agent of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). The latter is associated with case fatality rates ranging from 30% to 50%. HCPS cases are rare, with approximately 300 recorded annually in the Americas. Recently, an HCPS outbreak of unprecedented size has been occurring in and around Epuyén, in the southwestern Argentinian state of Chubut. Since November of 2018, at least 29 cases have been laboratory confirmed, and human-to-human transmission is suspected. Despite posing a significant threat to public health, no treatment or vaccine is available for hantaviral disease. Here, we describe an effort to identify, characterize, and develop neutralizing and protective antibodies against the glycoprotein complex (Gn and Gc) of Andes virus (ANDV), the causative agent of the Epuyén outbreak. Using murine hybridoma technology, we generated 19 distinct monoclonal antibodies (MAbs) against ANDV GnGc. When tested for neutralization against a recombinant vesicular stomatitis virus expressing the Andes glycoprotein (GP) (VSV-ANDV), 12 MAbs showed potent neutralization and 8 showed activity in an antibody-dependent cellular cytotoxicity reporter assay. Escape mutant analysis revealed that neutralizing MAbs targeted both the Gn and the Gc. Four MAbs that bound different epitopes were selected for preclinical studies and were found to be 100% protective against lethality in a Syrian hamster model of ANDV infection. These data suggest the existence of a wide array of neutralizing antibody epitopes on hantavirus GnGc with unique properties and mechanisms of action.IMPORTANCE Infections with New World hantaviruses are associated with high case fatality rates, and no specific vaccine or treatment options exist. Furthermore, the biology of the hantaviral GnGc complex, its antigenicity, and its fusion machinery are poorly understood. Protective monoclonal antibodies against GnGc have the potential to be developed into therapeutics against hantaviral disease and are also great tools to elucidate the biology of the glycoprotein complex.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Infecções por Hantavirus/prevenção & controle , Orthohantavírus/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Cricetinae , Modelos Animais de Doenças , Epitopos/imunologia , Epitopos/metabolismo , Feminino , Infecções por Hantavirus/imunologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
The recent emergence of Zika virus (ZIKV) has been concentrated in the Caribbean, Southeastern United States, and South- and Central America; resulting in travel-based cases being reported around the globe. As multi-disciplinary collaborations are combatting the ZIKV outbreak, the need to validate the sequence of existing strains has become apparent. Here, we report high-quality sequence data for multiple ZIKV strains made publicly available through the National Institutes of Health- (NIH) funded biorepository, BEI Resources (www.beiresources.org). Next-generation sequencing, 3' rapid amplification of cDNA ends (RACE), and viral genome annotation pipelines generated GenBank sequence records for 16 BEI Resources strains. Minor variants, consensus mutations, and consensus insertions/deletions were identified within the viral stocks using next-generation sequencing (NGS) and consensus changes were confirmed with Sanger sequencing. Bioinformatics analyses of the sequencing results confirm that the virus stocks available to the scientific research community through BEI Resources adequately represent the viral population diversity of ZIKV.
Assuntos
Variação Genética , Genoma Viral , Zika virus/genética , Bases de Dados de Ácidos Nucleicos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Filogenia , RNA Viral/química , RNA Viral/genética , Recombinação Genética , Sequenciamento Completo do Genoma , Zika virus/classificação , Infecção por Zika virus/virologiaRESUMO
We report here the whole-genome sequence of 11 Zika virus (ZIKV) samples from six pediatric patients in Nicaragua. Serum samples were collected, and ZIKV was isolated in tissue culture. Both serum and virus isolates were sequenced. The consensus ZIKV genomes are greater than 99% identical to each other.
RESUMO
We report 26 complete genomes of Zika virus (ZIKV) isolated after passaging the Zika virus strain FLR in mosquito (C6/36) and mammalian (Vero) cell lines. The consensus ZIKV genomes we recovered show greater than 99% nucleotide identify with each other and with the FLR strain used as input.
RESUMO
Examining the patterns of archaeal diversity in little-explored organic-lean marine subsurface sediments presents an opportunity to study the association of phylogenetic affiliation and habitat preference in uncultured marine Archaea. Here we have compiled and re-analyzed published archaeal 16S rRNA clone library datasets across a spectrum of sediment trophic states characterized by a wide range of terminal electron-accepting processes. Our results show that organic-lean marine sediments in deep marine basins and oligotrophic open ocean locations are inhabited by distinct lineages of archaea that are not found in the more frequently studied, organic-rich continental margin sediments. We hypothesize that different combinations of electron donor and acceptor concentrations along the organic-rich/organic-lean spectrum result in distinct archaeal communities, and propose an integrated classification of habitat characteristics and archaeal community structure.
RESUMO
Abyssal marine sediments cover a large proportion of the ocean floor, but linkages between their microbial community structure and redox stratification have remained poorly constrained. This study compares the downcore gradients in microbial community composition to porewater oxygen and nitrate concentration profiles in an abyssal marine sediment column in the South Pacific Ocean. Archaeal 16S rRNA clone libraries showed a stratified archaeal community that changed from Marine Group I Archaea in the aerobic and nitrate-reducing upper sediment column towards deeply branching, uncultured crenarchaeotal and euryarchaeotal lineages in nitrate-depleted, anaerobic sediment horizons. Bacterial 16S rRNA clone libraries revealed a similar shift on the phylum and subphylum level within the bacteria, from a complex community of Alpha-, Gamma- and Deltaproteobacteria, Actinobacteria and Gemmatimonadetes in oxic surface sediments towards uncultured Chloroflexi and Planctomycetes in the anaerobic sediment column. The distinct stratification of largely uncultured bacterial and archaeal groups within the oxic and nitrate-reducing marine sediment column provides initial constraints for their microbial habitat preferences.
Assuntos
Archaea/classificação , Bactérias/classificação , Ecossistema , Sedimentos Geológicos/microbiologia , Filogenia , Archaea/genética , Bactérias/genética , Biblioteca Gênica , Nitrogênio/análise , Oxigênio/análise , Oceano Pacífico , RNA Arqueal/genética , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Água do Mar/química , Água do Mar/microbiologia , Análise de Sequência de RNARESUMO
Although oligotrophic, abyssal marine sediments cover most of the sea bottom, previous investigations of microbial diversity have primarily focused on organic-rich, anoxic sediments of continental margins. In contrast, abyssal open-ocean sediments are oxidized and contain limiting organic substrate concentrations. This study examines the archaeal diversity of oligotrophic, oxic and nitrate-reducing marine sediments and oxic bottom water in the South Pacific Gyre. 16S rDNA clone library analysis identified phylogenetically distinct lineages of the Marine Group I (MG-I) Crenarchaeota in oxidized sediment that are different from those in bottom water. Thus, the sediment habitat selects for different MG-I lineages, within short vertical distances of a few centimetres.