Although millions of distinct virus species likely exist, only approximately 9000 are catalogued in GenBank's RefSeq database. We selectively enriched for the genomes of circular DNA viruses in over ...70 animal samples, ranging from nematodes to human tissue specimens. A bioinformatics pipeline, Cenote-Taker, was developed to automatically annotate over 2500 complete genomes in a GenBank-compliant format. The new genomes belong to dozens of established and emerging viral families. Some appear to be the result of previously undescribed recombination events between ssDNA and ssRNA viruses. In addition, hundreds of circular DNA elements that do not encode any discernable similarities to previously characterized sequences were identified. To characterize these 'dark matter' sequences, we used an artificial neural network to identify candidate viral capsid proteins, several of which formed virus-like particles when expressed in culture. These data further the understanding of viral sequence diversity and allow for high throughput documentation of the virosphere.
Enterovirus D68 (EV-D68) infection has been associated with outbreaks of severe respiratory illness and increased cases of nonpolio acute flaccid myelitis. The patterns of EV-D68 circulation and ...molecular epidemiology are not fully understood. In this study, nasopharyngeal (NP) specimens collected from patients in the Lower Hudson Valley, New York, from 2014 to 2018 were examined for rhinovirus/enterovirus (RhV/EV) by the FilmArray respiratory panel. Selected RhV/EV-positive NP specimens were analyzed using two EV-D68-specific real-time RT-PCR assays, Sanger sequencing and metatranscriptomic next-generation sequencing. A total of 2,398 NP specimens were examined. EV-D68 was detected in 348 patients with NP specimens collected in 2014 (
= 94), 2015 (
= 0), 2016 (
= 160), 2017 (
= 5), and 2018 (
= 89), demonstrating a biennial upsurge of EV-D68 infection in the study area. Ninety-one complete or nearly complete EV-D68 genome sequences were obtained. Genomic analysis of these EV-D68 strains revealed dynamics and evolution of circulating EV-D68 strains since 2014. The dominant EV-D68 strains causing the 2014 outbreak belonged to subclade B1, with a few belonging to subclade B2. New EV-D68 subclade B3 strains emerged in 2016 and continued in circulation in 2018. Clade D strains that are rarely detected in the United States also arose and spread in 2018. The establishment of distinct viral strains and their variable circulation patterns provide essential information for future surveillance, diagnosis, vaccine development, and prediction of EV-D68-associated disease prevalence and potential outbreaks.
Background SARS-CoV-2 remains rapidly evolving, and many biologically important genomic substitutions/indels have characterised novel SARS-CoV-2 lineages, which have emerged during successive global ...waves of the pandemic. Worldwide genomic sequencing has been able to monitor these waves, track transmission clusters, and examine viral evolution in real time to help inform healthcare policy. One school of thought is that an apparent greater than average divergence in an emerging lineage from contemporary variants may require persistent infection, for example in an immunocompromised host. Due to the nature of the COVID-19 pandemic and sampling, there were few studies that examined the evolutionary trajectory of SARS-CoV-2 in healthy individuals. Methods We investigated viral evolutionary trends and participant symptomatology within a cluster of 16 SARS-CoV-2 infected, immunocompetent individuals with no co-morbidities in a closed transmission chain. Longitudinal nasopharyngeal swab sampling allowed characterisation of SARS-CoV-2 intra-host variation over time at both the dominant and minor genomic variant levels through Nimagen-Illumina sequencing. Results A change in viral lineage assignment was observed in individual infections; however, there was only one indel and no evidence of recombination over the period of an acute infection. Minor and dominant genomic modifications varied between participants, with some minor genomic modifications increasing in abundance to become the dominant viral sequence during infection. Conclusions Data from this cohort of SARS-CoV-2-infected participants demonstrated that long-term persistent infection in an immunocompromised host was not necessarily a prerequisite for generating a greater than average frequency of amino acid substitutions. Amino acid substitutions at both the dominant and minor genomic sequence level were observed in immunocompetent individuals during infection showing that viral lineage changes can occur generating viral diversity. Keywords: SARS-CoV-2, Transmission cluster, Viral evolution, Minor variants
The COVID-19 pandemic has brought significant challenges for genomic surveillance strategies in public health systems worldwide. During the past thirty-four months, many countries faced several ...epidemic waves of SARS-CoV-2 infections, driven mainly by the emergence and spread of novel variants. In that line, genomic surveillance has been a crucial toolkit to study the real-time SARS-CoV-2 evolution, for the assessment and optimization of novel diagnostic assays, and to improve the efficacy of existing vaccines. During the pandemic, the identification of emerging lineages carrying lineage-specific mutations (particularly those in the Receptor Binding domain) showed how these mutations might significantly impact viral transmissibility, protection from reinfection and vaccination. So far, an unprecedented number of SARS-CoV-2 viral genomes has been released in public databases (i.e., GISAID, and NCBI), achieving 14 million genome sequences available as of early-November 2022. In the present review, we summarise the global landscape of SARS-CoV-2 during the first thirty-four months of viral circulation and evolution. It demonstrates the urgency and importance of sustained investment in genomic surveillance strategies to timely identify the emergence of any potential viral pathogen or associated variants, which in turn is key to epidemic and pandemic preparedness.
•Following the real-time evolution of SARS-CoV-2, an emerging threat of international concern.•Using High Throughput Sequencing strategies will allow identification of VOCs which in turn will improve the global pandemic response.•The global genomic pandemic response needs to be improved to prevent other spillover and spillback events
Obesity is associated with increased disease severity, elevated viral titers in exhaled breath, and significantly prolonged viral shed during influenza A virus infection. Due to the mutable nature of ...RNA viruses, we questioned whether obesity could also influence influenza virus population diversity. Here, we show that minor variants rapidly emerge in obese mice. The variants exhibit increased viral replication, resulting in enhanced virulence in wild-type mice. The increased diversity of the viral population correlated with decreased type I interferon responses, and treatment of obese mice with recombinant interferon reduced viral diversity, suggesting that the delayed antiviral response exhibited in obesity permits the emergence of a more virulent influenza virus population. This is not unique to obese mice. Obesity-derived normal human bronchial epithelial (NHBE) cells also showed decreased interferon responses and increased viral replication, suggesting that viral diversity also was impacted in this increasing population.
Currently, 50% of the adult population worldwide is overweight or obese. In these studies, we demonstrate that obesity not only enhances the severity of influenza infection but also impacts viral diversity. The altered microenvironment associated with obesity supports a more diverse viral quasispecies and affords the emergence of potentially pathogenic variants capable of inducing greater disease severity in lean hosts. This is likely due to the impaired interferon response, which is seen in both obese mice and obesity-derived human bronchial epithelial cells, suggesting that obesity, aside from its impact on influenza virus pathogenesis, permits the stochastic accumulation of potentially pathogenic viral variants, raising concerns about its public health impact as the prevalence of obesity continues to rise.
The first step of viral evolution takes place during genome replication via the error-prone viral polymerase. Among the mutants that arise through this process, only a few well-adapted variants will ...be selected by natural selection, renewing the viral genome population. Viral polymerase-mediated errors are thought to occur stochastically. However, accumulating evidence suggests that viral polymerase-mediated mutations are heterogeneously distributed throughout the viral genome. Here, we review work that supports this concept and provides mechanistic insights into how specific features of the viral genome could modulate viral polymerase-mediated errors. A predisposition to accumulate viral polymerase-mediated errors at specific loci in the viral genome may guide evolution to specific pathways, thus opening new directions of research to better understand viral evolutionary dynamics.
Emerging infectious diseases are a major challenge to human and animal health. While predicting the emergence of pathogens is complex, the advent of high-throughput sequencing technologies has ...allowed the rapid identification of unknown microbiology diversity within organisms. Here, we discuss an example of a metatranscriptomics output to decipher viral evolution.
The spike glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to accumulate substitutions, leading to breakthrough infections of vaccinated individuals. It remains ...unclear if exposures to antigenically distant SARS-CoV-2 variants can overcome memory B cell biases established by initial SARS-CoV-2 encounters. We determined the specificity and functionality of antibody and B cell responses following exposure to BA.5 and XBB variants in individuals who received ancestral SARS-CoV-2 mRNA vaccines. BA.5 exposures elicited antibody responses that targeted epitopes conserved between the BA.5 and ancestral spike. XBB exposures also elicited antibody responses that primarily targeted epitopes conserved between the XBB.1.5 and ancestral spike. However, unlike BA.5, a single XBB exposure elicited low frequencies of XBB.1.5-specific antibodies and B cells in some individuals. Pre-existing cross-reactive B cells and antibodies were correlated with stronger overall responses to XBB but weaker XBB-specific responses, suggesting that baseline immunity influences the activation of variant-specific SARS-CoV-2 responses.
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•Variant breakthrough infections boost ancestral cross-reactive antibodies and B cells•First and second BA.5 exposures fail to elicit variant-specific antibodies and B cells•XBB infections and vaccinations elicit XBB-specific responses in some individuals•XBB-specific responses correlate with low levels of pre-existing humoral immunity
It is unknown if antigenically distant SARS-CoV-2 variants can overcome memory B cell biases established by initial SARS-CoV-2 encounters. Johnston, Painter, Li et al. show that BA.5 and XBB exposures recall B cells targeting conserved epitopes in the ancestral SARS-CoV-2 spike protein. They found instances of XBB-specific responses after XBB exposures, which correlated with low baseline levels of humoral immunity.
SARS-CoV-2 humoral immunity in people living with HIV-1 Motsoeneng, Boitumelo M.; Bhiman, Jinal N.; Richardson, Simone I. ...
Trends in immunology,
July 2024, 2024-07-00, 20240701, Letnik:
45, Številka:
7
Journal Article
Recenzirano
Odprti dostop
People living with HIV-1 (PLWH) on antiretroviral treatment (ART) present with delayed infection- and vaccine-induced humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ...compared with people without HIV-1 (PWOH). However, they eventually reach titers equivalent to those of PWOH.Differential coordination of SARS-CoV-2 Fc effector functions suggests that antibody responses are qualitatively variable in PLWH, with potential implications for vaccination.Intrahost diversity is more pronounced in ART-naive PLWH, who may contribute to the divergence of SARS-CoV-2 lineages and/or the emergence of variants of concern.Existing data on SARS-CoV-2 humoral immunity and intrahost diversity in PLWH supports the need to increase access to ART.
Given the substantial number of people living with HIV-1 (PLWH), especially in sub-Saharan Africa, understanding the effectiveness of COVID-19 vaccines and antibody responses to SARS-CoV-2 infection and vaccination is essential. Additionally, the impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in PLWH remains underexplored. Prolonged SARS-CoV-2 shedding, and enhanced intrahost diversity observed for PLWH, might be one of the driving forces behind SARS-CoV-2 evolution in Africa and should be further considered, with public health implications worldwide.
The effect of COVID-19 on the high number of immunocompromised people living with HIV-1 (PLWH), particularly in Africa, remains a critical concern. Here, we identify key areas that still require further investigation, by examining COVID-19 vaccine effectiveness, and understanding antibody responses in SARS-CoV-2 infection and vaccination in comparison with people without HIV-1 (PWOH). We also assess the potential impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in these individuals. Lastly, we discuss the consequences of persistent infection in PLWH (or other immunocompromised individuals), including prolonged shedding, increased viral diversity within the host, and the implications on SARS-CoV-2 evolution in Africa.
The effect of COVID-19 on the high number of immunocompromised people living with HIV-1 (PLWH), particularly in Africa, remains a critical concern. Here, we identify key areas that still require further investigation, by examining COVID-19 vaccine effectiveness, and understanding antibody responses in SARS-CoV-2 infection and vaccination in comparison with people without HIV-1 (PWOH). We also assess the potential impact of pre-existing immunity against endemic human coronaviruses on SARS-CoV-2 responses in these individuals. Lastly, we discuss the consequences of persistent infection in PLWH (or other immunocompromised individuals), including prolonged shedding, increased viral diversity within the host, and the implications on SARS-CoV-2 evolution in Africa.
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