scholarly journals Population Bottlenecks and Intra-host Evolution during Human-to-Human Transmission of SARS-CoV-2

2020 ◽  
Author(s):  
Daxi Wang ◽  
Yanqun Wang ◽  
Wanying Sun ◽  
Lu Zhang ◽  
Jingkai Ji ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Viral Replication ◽  
Evolutionary Dynamics ◽  
Stochastic Dynamics ◽  
Considerable Proportion ◽  
Messenger Rnas ◽  
Active Viral Replication ◽  
Replication Activity ◽  
Transmission Bottleneck

AbstractThe emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.Author summaryIn this study, we compared SARS-CoV-2 populations of 13 Chinese COVID-19 patients. Those viral populations contained a considerable proportion of viral sub-genomic messenger RNAs (sgmRNA), reflecting an active viral replication activity in the respiratory tract tissues. The comparison of 66 identified intra-host variants further showed a low viral genetic distance between intra-household patients and a narrow transmission bottleneck size. Despite the co-existence of genetically distinct viruses within the same host, most intra-host minor variants were not shared between transmission pairs, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Furthermore, the narrow bottleneck and active viral activity in the respiratory tract show that the passage of a small number of virions can cause infection. Our data have therefore delivered a key genomic resource for the SARS-CoV-2 transmission research and enhanced our understanding of the evolutionary dynamics of SARS-CoV-2.

scholarly journals Population Bottlenecks and Intra-host Evolution During Human-to-Human Transmission of SARS-CoV-2

2021 ◽  
Vol 8 ◽  
Author(s):  
Daxi Wang ◽  
Yanqun Wang ◽  
Wanying Sun ◽  
Lu Zhang ◽  
Jingkai Ji ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Stochastic Dynamics ◽  
The Novel ◽  
Population Bottlenecks ◽  
Human Respiratory Tract ◽  
Human Coronavirus ◽  
Active Viral Replication ◽  
Host Evolution ◽  
Replication Activity

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.

Role of hepatitis E virus antigen in confirming active viral replication in patients with acute viral hepatitis E infection

2013 ◽  
Vol 58 (2) ◽  
pp. 374-377 ◽  
Author(s):  
Ekta Gupta ◽  
Priyanka Pandey ◽  
Shivani Pandey ◽  
Manoj Kumar Sharma ◽  
Shiv Kumar Sarin
Keyword(s):  
Viral Replication ◽  
Viral Hepatitis ◽  
Hepatitis E Virus ◽  
Acute Viral Hepatitis ◽  
Hepatitis E ◽  
Virus Antigen ◽  
Active Viral Replication

scholarly journals Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics

2021 ◽  
Vol 218 (8) ◽  
Author(s):  
Nagarjuna R. Cheemarla ◽  
Timothy A. Watkins ◽  
Valia T. Mihaylova ◽  
Bao Wang ◽  
Dejian Zhao ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Viral Replication ◽  
Innate Immune ◽  
Airway Epithelial ◽  
Upper Respiratory Tract ◽  
Infectious Dose ◽  
Interferon Stimulated Genes ◽  
Upper Respiratory ◽  
Early Replication

Initial replication of SARS-CoV-2 in the upper respiratory tract is required to establish infection, and the replication level correlates with the likelihood of viral transmission. Here, we examined the role of host innate immune defenses in restricting early SARS-CoV-2 infection using transcriptomics and biomarker-based tracking in serial patient nasopharyngeal samples and experiments with airway epithelial organoids. SARS-CoV-2 initially replicated exponentially, with a doubling time of ∼6 h, and induced interferon-stimulated genes (ISGs) in the upper respiratory tract, which rose with viral replication and peaked just as viral load began to decline. Rhinovirus infection before SARS-CoV-2 exposure accelerated ISG responses and prevented SARS-CoV-2 replication. Conversely, blocking ISG induction during SARS-CoV-2 infection enhanced viral replication from a low infectious dose. These results show that the activity of ISG-mediated defenses at the time of SARS-CoV-2 exposure impacts infection progression and that the heterologous antiviral response induced by a different virus can protect against SARS-CoV-2.

scholarly journals The ITAM in Nef Influences Acute Pathogenesis of AIDS-Inducing Simian Immunodeficiency Viruses SIVsm and SIVagm without Altering Kinetics or Extent of Viremia

2002 ◽  
Vol 76 (9) ◽  
pp. 4379-4389 ◽  
Author(s):  
Houman Dehghani ◽  
Charles R. Brown ◽  
Ronald Plishka ◽  
Alicia Buckler-White ◽  
Vanessa M. Hirsch
Keyword(s):  
Viral Replication ◽  
Simian Immunodeficiency Virus ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Macaca Nemestrina ◽  
Viral Reservoir ◽  
Immunodeficiency Virus ◽  
Active Viral Replication ◽  
Activation Motif

ABSTRACT The role of the immunoreceptor tyrosine-based activation motif (ITAM) that is unique to the Nef protein of the acutely pathogenic simian immunodeficiency virus SIVsmPBj was studied in the context of two AIDS-inducing simian immunodeficiency virus molecular clones. NefY+ variants of SIVagm9063-2 and SIVsmE543-3 replicated in and induced proliferation of unstimulated pig-tailed macaque PBMC. The pathogenesis of the NefY+ and NefY− clones of SIVagm9063-2, SIVsmE543-3, and PBj6.6 were evaluated by intravenous inoculation of pig-tailed macaques (Macaca nemestrina). Introduction of the ITAM did not increase plasma viral RNA levels nor alter the kinetics of viremia compared with the NefY− versions of each clone. Clinical symptoms were not observed in animals inoculated with the NefY− variants. In contrast, characteristic PBj symptoms were observed in animals inoculated with any of the three NefY+ clones. Blunting and fusion of intestinal villi and multifocal infiltration of mononuclear cells were observed in the gastrointestinal tracts of macaques inoculated with the NefY+ versions. Lesions were associated with active viral replication, as demonstrated by simian immunodeficiency virus-specific in situ hybridization. However, only the macaque inoculated with wild-type NefY+ SIVsmPBj developed fatal disease; lesions were more widespread and severe in this animal. A switch to macrophages as a viral reservoir and the presence of interleukin-6 in plasma was unique to the macaque infected with PBj6.6. Overall, these data suggest that the ITAM in SIV Nef alters the pathogenesis of simian immunodeficiency virus regardless of the viral background. The change in pathogenesis occurs without enhancement of viral replication. However, NefY+ variants of SIVagm and SIVsm did not fully recapitulate the virulence of SIVsmPBj, implicating additional viral factors in this unique virus pathogenesis.

Computational Approaches for the Discovery of Novel Hepatitis C Virus NS3/4A and NS5B Inhibitors

2015 ◽  
pp. 318-353
Author(s):  
Khac-Minh Thai ◽  
Quoc-Hiep Dong ◽  
Thi-Thanh-Lan Nguyen ◽  
Duy-Phong Le ◽  
Minh-Tri Le ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Discovery ◽  
Virtual Screening ◽  
Viral Replication ◽  
Quantitative Structure Activity Relationship ◽  
Computational Approaches ◽  
Ns5b Polymerase ◽  
Replication Activity

Nonstructural 5B (NS5B) polymerase and Nonstructural 3/4A (NS3/4A) protease have proven to be promising targets for the development of anti-HCV (Hepatitis C Virus) agents. The NS5B polymerase is of paramount importance in HCV viral replication; therefore, employing NS5B inhibitors was considered an effective way for the treatment of HCV. Identifying inhibitors against NS3/4A serine protease represents another attractive approach applied in anti-HCV drug discovery, which is evidenced by its crucial role of in the biogenesis of the viral replication activity. In this chapter, many different computational approaches including Quantitative Structure-Activity Relationship (QSAR) and virtual screening in anti-HCV drug discovery were considered and discussed in detail. Virtual Screening (VS) techniques, including ligand-based and structure-based, and QSAR have been utilized for the discovery of NS5B inhibitors. Moreover, using various in silico protocols and workflows, a number of studies have been conducted with an aim of identifying potential NS3/4A blockage agents.

Computational Approaches for the Discovery of Novel Hepatitis C Virus NS3/4A and NS5B Inhibitors

Oncology ◽  
2017 ◽  
pp. 482-518 ◽  
Author(s):  
Khac-Minh Thai ◽  
Quoc-Hiep Dong ◽  
Thi-Thanh-Lan Nguyen ◽  
Duy-Phong Le ◽  
Minh-Tri Le ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Discovery ◽  
Virtual Screening ◽  
Viral Replication ◽  
Quantitative Structure Activity Relationship ◽  
Computational Approaches ◽  
Ns5b Polymerase ◽  
Replication Activity

Nonstructural 5B (NS5B) polymerase and Nonstructural 3/4A (NS3/4A) protease have proven to be promising targets for the development of anti-HCV (Hepatitis C Virus) agents. The NS5B polymerase is of paramount importance in HCV viral replication; therefore, employing NS5B inhibitors was considered an effective way for the treatment of HCV. Identifying inhibitors against NS3/4A serine protease represents another attractive approach applied in anti-HCV drug discovery, which is evidenced by its crucial role of in the biogenesis of the viral replication activity. In this chapter, many different computational approaches including Quantitative Structure-Activity Relationship (QSAR) and virtual screening in anti-HCV drug discovery were considered and discussed in detail. Virtual Screening (VS) techniques, including ligand-based and structure-based, and QSAR have been utilized for the discovery of NS5B inhibitors. Moreover, using various in silico protocols and workflows, a number of studies have been conducted with an aim of identifying potential NS3/4A blockage agents.

scholarly journals Landscape resistance constrains hybridization across contact zones in a reproductively and morphologically polymorphic salamander

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Guillermo Velo-Antón ◽  
André Lourenço ◽  
Pedro Galán ◽  
Alfredo Nicieza ◽  
Pedro Tarroso
Keyword(s):  
Contact Zone ◽  
Environmental Heterogeneity ◽  
Evolutionary Dynamics ◽  
Morphological Differentiation ◽  
Phenotypic Traits ◽  
Hybrid Zones ◽  
Landscape Resistance ◽  
Phenotypic Differentiation ◽  
Contact Zones

AbstractExplicitly accounting for phenotypic differentiation together with environmental heterogeneity is crucial to understand the evolutionary dynamics in hybrid zones. Species showing intra-specific variation in phenotypic traits that meet across environmentally heterogeneous regions constitute excellent natural settings to study the role of phenotypic differentiation and environmental factors in shaping the spatial extent and patterns of admixture in hybrid zones. We studied three environmentally distinct contact zones where morphologically and reproductively divergent subspecies of Salamandra salamandra co-occur: the pueriparous S. s. bernardezi that is mostly parapatric to its three larviparous subspecies neighbours. We used a landscape genetics framework to: (i) characterise the spatial location and extent of each contact zone; (ii) assess patterns of introgression and hybridization between subspecies pairs; and (iii) examine the role of environmental heterogeneity in the evolutionary dynamics of hybrid zones. We found high levels of introgression between parity modes, and between distinct phenotypes, thus demonstrating the evolution to pueriparity alone or morphological differentiation do not lead to reproductive isolation between these highly divergent S. salamandra morphotypes. However, we detected substantial variation in patterns of hybridization across contact zones, being lower in the contact zone located on a topographically complex area. We highlight the importance of accounting for spatial environmental heterogeneity when studying evolutionary dynamics of hybrid zones.

scholarly journals The lung microbiota in Korean patients with non-tuberculous mycobacterial pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sung-Yoon Kang ◽  
Hyojung Kim ◽  
Sungwon Jung ◽  
Sang Min Lee ◽  
Sang Pyo Lee
Keyword(s):  
Principal Component Analysis ◽  
Respiratory Tract ◽  
Pulmonary Disease ◽  
Beta Diversity ◽  
Lower Respiratory Tract ◽  
Principal Component ◽  
Control Group ◽  
Flexible Bronchoscope ◽  
Bronchial Washing

Abstract Background The microbiota of the lower respiratory tract in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) has not been fully evaluated. We explored the role of the lung microbiota in NTM-PD by analyzing protected specimen brushing (PSB) and bronchial washing samples from patients with NTM-PD obtained using a flexible bronchoscope. Results Bronchial washing and PSB samples from the NTM-PD group tended to have fewer OTUs and lower Chao1 richness values compared with those from the control group. In both bronchial washing and PSB samples, beta diversity was significantly lower in the NTM-PD group than in the control group (P = 2.25E-6 and P = 4.13E-4, respectively). Principal component analysis showed that the PSBs and bronchial washings exhibited similar patterns within each group but differed between the two groups. The volcano plots indicated differences in several phyla and genera between the two groups. Conclusions The lower respiratory tract of patients with NTM-PD has a unique microbiota distribution that is low in richness/diversity.

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