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BACKGROUND: Aedes-borne arboviruses cause both seasonal epidemics and emerging outbreaks with a significant impact on global health. These viruses share mosquito vector species, often infecting the same host population within overlapping geographic regions. Thus, comparative analyses of the virus evolutionary and epidemiological dynamics across spatial and temporal scales could reveal convergent trends. METHODOLOGY/PRINCIPAL FINDINGS: Focusing on Mexico as a case study, we generated novel chikungunya and dengue (CHIKV, DENV-1 and DENV-2) virus genomes from an epidemiological surveillance-derived historical sample collection, and analysed them together with longitudinally-collected genome and epidemiological data from the Americas. Aedes-borne arboviruses endemically circulating within the country were found to be introduced multiple times from lineages predominantly sampled from the Caribbean and Central America. For CHIKV, at least thirteen introductions were inferred over a year, with six of these leading to persistent transmission chains. For both DENV-1 and DENV-2, at least seven introductions were inferred over a decade. CONCLUSIONS/SIGNIFICANCE: Our results suggest that CHIKV, DENV-1 and DENV-2 in Mexico share evolutionary and epidemiological trajectories. The southwest region of the country was determined to be the most likely location for viral introductions from abroad, with a subsequent spread into the Pacific coast towards the north of Mexico. Virus diffusion patterns observed across the country are likely driven by multiple factors, including mobility linked to human migration from Central towards North America. Considering Mexico's geographic positioning displaying a high human mobility across borders, our results prompt the need to better understand the role of anthropogenic factors in the transmission dynamics of Aedes-borne arboviruses, particularly linked to land-based human migration.
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Aedes , Arbovírus , Humanos , Animais , México/epidemiologia , Arbovírus/genética , América Central/epidemiologia , América do NorteRESUMO
Over 200 different SARS-CoV-2 lineages have been observed in Mexico by November 2021. To investigate lineage replacement dynamics, we applied a phylodynamic approach and explored the evolutionary trajectories of five dominant lineages that circulated during the first year of local transmission. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in Mexico. Lineages B.1.1.222 and B.1.1.519 exhibited similar dynamics, constituting clades that likely originated in Mexico and persisted for >12 months. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. For the largest B.1.617.2 clades, we further explored viral lineage movements across Mexico. Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.
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COVID-19 , Humanos , México/epidemiologia , COVID-19/epidemiologia , SARS-CoV-2/genética , Evolução Biológica , FilogeniaRESUMO
During the coronavirus disease 2019 (COVID-19) pandemic, the emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in the United Kingdom in September 2020, was well documented in different areas of the world and became a global public health concern because of its increased transmissibility. The B.1.1.7 lineage was first detected in Mexico during December 2020, showing a slow progressive increase in its circulation frequency, which reached its maximum in May 2021 but never became predominant. In this work, we analyzed the patterns of diversity and distribution of this lineage in Mexico using phylogenetic and haplotype network analyses. Despite the reported increase in transmissibility of the B.1.1.7 lineage, in most Mexican states, it did not displace cocirculating lineages, such as B.1.1.519, which dominated the country from February to May 2021. Our results show that the states with the highest prevalence of B.1.1.7 were those at the Mexico-U.S. border. An apparent pattern of dispersion of this lineage from the northern states of Mexico toward the center or the southeast was observed in the largest transmission chains, indicating possible independent introduction events from the United States. However, other entry points cannot be excluded, as shown by multiple introduction events. Local transmission led to a few successful haplotypes with a localized distribution and specific mutations indicating sustained community transmission. IMPORTANCE The emergence and rapid increase of the B.1.1.7 (Alpha) lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the world were due to its increased transmissibility. However, it did not displace cocirculating lineages in most of Mexico, particularly B.1.1.519, which dominated the country from February to May 2021. In this work, we analyzed the distribution of B.1.1.7 in Mexico using phylogenetic and haplotype network analyses. Our results show that the states with the highest prevalence of B.1.1.7 (around 30%) were those at the Mexico-U.S. border, which also exhibited the highest lineage diversity, indicating possible introduction events from the United States. Also, several haplotypes were identified with a localized distribution and specific mutations, indicating that sustained community transmission occurred in the country.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Genoma Viral , Humanos , México/epidemiologia , Filogenia , SARS-CoV-2/genéticaRESUMO
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has shown a wide spectrum of clinical manifestations ranging from asymptomatic infections to severe disease and death. Pre-existing medical conditions and age have been mainly linked to the development of severe disease; however, the potential association of viral genetic characteristics with different clinical conditions remains unclear. SARS-CoV-2 variants with increased transmissibility were detected early in the pandemics, and several variants with potential relevance for public health are currently circulating around the world. In this study, we characterized 57 complete SARS-CoV-2 genomes during the exponential growth phase of the early epidemiological curve in Mexico, in April 2020. Patients were categorized under distinct disease severity outcomes: mild disease or ambulatory care, severe disease or hospitalized, and deceased. To reduce bias related to risk factors, the patients were less than 60 years old and with no diagnosed comorbidities A trait-association phylogenomic approach was used to explore genotype-phenotype associations, represented by the co-occurrence of mutations, disease severity outcome categories, and clusters of Mexican sequences. Phylogenetic results revealed a higher genomic diversity compared to the initial viruses detected during the early stage of the local epidemic. We identified a total of 90 single nucleotide variants compared to the Wuhan-Hu-1 genome, including 54 nonsynonymous mutations. We did not find evidence for the co-occurrence of mutations associated with specific disease outcomes. Therefore, in the group of patients studied, disease severity was likely mainly driven by the host genetic background and other demographic factors. IMPORTANCE The genetic association of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with different clinical conditions remains unclear and needs further investigation. In this study, we characterized 57 complete SARS-CoV-2 genomes from patients in Mexico with distinct disease severity outcomes: mild disease or ambulatory care, severe disease or hospitalized, and deceased. To reduce bias related to risk factors the patients were less than 60 years old and with no diagnosed comorbidities. We did not find evidence for the co-occurrence of mutations associated with specific disease outcomes. Therefore, in the group of patients studied, disease severity was likely mainly driven by the host genetic background and other demographic factors.
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COVID-19/epidemiologia , Genoma Viral , SARS-CoV-2/genética , Adulto , Fatores Etários , Assistência Ambulatorial/estatística & dados numéricos , COVID-19/complicações , COVID-19/mortalidade , Análise por Conglomerados , Feminino , Genótipo , Hospitalização/estatística & dados numéricos , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Mutação , Fenótipo , Filogenia , Cobertura de Condição Pré-Existente/estatística & dados numéricos , SARS-CoV-2/classificação , SARS-CoV-2/isolamento & purificação , Adulto JovemRESUMO
Characterisation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic diversity through space and time can reveal trends in virus importation and domestic circulation and permit the exploration of questions regarding the early transmission dynamics. Here, we present a detailed description of SARS-CoV-2 genomic epidemiology in Ecuador, one of the hardest hit countries during the early stages of the coronavirus-19 pandemic. We generated and analysed 160 whole genome sequences sampled from all provinces of Ecuador in 2020. Molecular clock and phylogeographic analysis of these sequences in the context of global SARS-CoV-2 diversity enable us to identify and characterise individual transmission lineages within Ecuador, explore their spatiotemporal distributions, and consider their introduction and domestic circulation. Our results reveal a pattern of multiple international importations across the country, with apparent differences between key provinces. Transmission lineages were mostly introduced before the implementation of non-pharmaceutical interventions, with differential degrees of persistence and national dissemination.
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Characterisation of SARS-CoV-2 genetic diversity through space and time can reveal trends in virus importation and domestic circulation, and permit the exploration of questions regarding the early transmission dynamics. Here we present a detailed description of SARS-CoV-2 genomic epidemiology in Ecuador, one of the hardest hit countries during the early stages of the COVID-19 pandemic. We generate and analyse 160 whole genome sequences sampled from all provinces of Ecuador in 2020. Molecular clock and phylgeographic analysis of these sequences in the context of global SARS-CoV-2 diversity enable us to identify and characterise individual transmission lineages within Ecuador, explore their spatiotemporal distributions, and consider their introduction and domestic circulation. Our results reveal a pattern of multiple international importations across the country, with apparent differences between key provinces. Transmission lineages were mostly introduced before the implementation of non-pharmaceutical interventions (NPIs), with differential degrees of persistence and national dissemination.
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The coronavirus disease 2019 (COVID-19) pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to enabling implementation of effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage A/G, containing mostly sequences from North America, and lineage B/S, containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized 14 independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represented local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified an H49Y amino acid change in the Spike protein. This mutation represents a homoplasy occurring independently through time and space and may function as a molecular marker to follow any further spread of these viral variants throughout the country. Our results provide a general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread, and establishment of SARS-CoV-2 within distinct human populations as well as the evolution of the pandemics is crucial to implement effective control strategies. In this work, we report that the initial virus strains introduced in Mexico came from Europe and the United States and that the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains with a H49Y mutation in the Spike protein, which could be further used as a molecular marker to follow viral spread within the country and the region.
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Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Variação Genética , Genoma Viral , Genômica , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Substituição de Aminoácidos , Betacoronavirus/classificação , COVID-19 , Biologia Computacional/métodos , Infecções por Coronavirus/transmissão , Genômica/métodos , Humanos , México/epidemiologia , Mutação , Pandemias , Filogenia , Pneumonia Viral/transmissão , SARS-CoV-2RESUMO
The Amazon basin is home to numerous arthropod-borne viral pathogens that cause febrile disease in humans. Among these, Oropouche orthobunyavirus (OROV) is a relatively understudied member of the genus Orthobunyavirus, family Peribunyaviridae, that causes periodic outbreaks in human populations in Brazil and other South American countries. Although several studies have described the genetic diversity of the virus, the evolutionary processes that shape the OROV genome remain poorly understood. Here, we present a comprehensive study of the genomic dynamics of OROV that encompasses phylogenetic analysis, evolutionary rate estimates, inference of natural selective pressures, recombination and reassortment, and structural analysis of OROV variants. Our study includes all available published sequences, as well as a set of new OROV genome sequences obtained from patients in Ecuador, representing the first set of genomes from this country. Our results show differing evolutionary processes on the three segments that comprise the viral genome. We infer differing times of the most recent common ancestors of the genome segments and propose that this can be explained by cryptic reassortment. We also present the discovery of previously unobserved putative N-linked glycosylation sites, as well as codons that evolve under positive selection on the viral surface proteins, and discuss the potential role of these features in the evolution of OROV through a combined phylogenetic and structural approach.IMPORTANCE The emergence and reemergence of pathogens such as Zika virus, chikungunya virus, and yellow fever virus have drawn attention toward other cocirculating arboviruses in South America. Oropouche virus (OROV) is a poorly studied pathogen responsible for over a dozen outbreaks since the early 1960s and represents a public health burden to countries such as Brazil, Panama, and Peru. OROV is likely underreported since its symptomatology can be easily confounded with other febrile illnesses (e.g., dengue fever and leptospirosis) and point-of-care testing for the virus is still uncommon. With limited data, there is a need to optimize the information currently available. Analysis of OROV genomes can help us understand how the virus circulates in nature and can reveal the evolutionary forces that shape the genetic diversity of the virus, which has implications for molecular diagnostics and the design of potential vaccines.
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Evolução Molecular , Genoma Viral , Orthobunyavirus/classificação , Orthobunyavirus/genética , Filogenia , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/virologia , Equador , Humanos , Modelos Moleculares , Conformação Proteica , Seleção Genética , América do Sul , Proteínas Virais/química , Proteínas Virais/genética , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Tuberculosis (TB) remains a serious human health problem that affects millions of people in the world. Understanding the biology of Mycobacterium tuberculosis (Mtb) is essential for tackling this devastating disease. Mtb possesses a very complex cell envelope containing a variety of lipid components that participate in the establishment of the infection. We have previously demonstrated that di-O-acylated trehalose (DAT), a non-covalently linked cell wall glycolipid, inhibits the proliferation of T lymphocytes and the production of cytokines. RESULTS: In this work we show that DAT and the closely related tri-O-acylated trehalose (TAT) inhibits nitric oxide (NO) production and the inducible nitric oxide synthase (iNOS) expression in macrophages (MØ). CONCLUSIONS: These findings show that DAT and TAT are cell-wall located virulence factors that downregulate an important effector of the immune response against mycobacteria.
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Glicolipídeos/farmacologia , Macrófagos/enzimologia , Mycobacterium/química , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/biossíntese , Trealose/farmacologia , Acilação/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Regulação para Baixo/efeitos dos fármacos , Glicolipídeos/isolamento & purificação , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Trealose/isolamento & purificaçãoRESUMO
In this work, nineteen influenza A/H3N2 viruses isolated in Mexico between 2003 and 2012 were studied. Our findings show that different human A/H3N2 viral lineages co-circulate within a same season and can also persist locally in between different influenza seasons, increasing the chance for genetic reassortment events. A novel minor cluster was also identified, named here as Korea, that circulated worldwide during 2003. Frequently, phylogenetic characterization did not correlate with the determined antigenic identity, supporting the need for the use of molecular evolutionary tools additionally to antigenic data for the surveillance and characterization of viral diversity during each flu season. This work represents the first long-term molecular epidemiology study of influenza A/H3N2 viruses in Mexico based on the complete genomic sequences and contributes to the monitoring of evolutionary trends of A/H3N2 influenza viruses within North and Central America.