Surveillance of Bat Coronaviruses in Kenya Identifies Relatives of Human Coronaviruses NL63 and 229E and Their Recombination History

ABSTRACT Bats harbor a large diversity of coronaviruses (CoVs), several of which are related to zoonotic pathogens that cause severe disease in humans. Our screening of bat samples collected in Kenya from 2007 to 2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E, suggesting that these two human viruses originate from bats. We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in Triaenops bats and 229E-like viruses circulating in Hipposideros bats, with the breakpoint located near 5′ and 3′ ends of the spike (S) protein gene. In addition, two further interspecies recombination events involving the S gene were identified, suggesting that this region may represent a recombination “hot spot” in CoV genomes. Finally, using a combination of phylogenetic and distance-based approaches, we showed that the genetic diversity of bat CoVs is primarily structured by host species and subsequently by geographic distances. IMPORTANCE Understanding the driving forces of cross-species virus transmission is central to understanding the nature of disease emergence. Previous studies have demonstrated that bats are the ultimate reservoir hosts for a number of coronaviruses (CoVs), including ancestors of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human CoV 229E (HCoV-229E). However, the evolutionary pathways of bat CoVs remain elusive. We provide evidence for natural recombination between distantly related African bat coronaviruses associated with Triaenops afer and Hipposideros sp. bats that resulted in a NL63-like virus, an ancestor of the human pathogen HCoV-NL63. These results suggest that interspecies recombination may play an important role in CoV evolution and the emergence of novel CoVs with zoonotic potential.

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Evolutionary trajectory of SARS-CoV-2 and emerging variants

Virology Journal ◽

10.1186/s12985-021-01633-w ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Jalen Singh ◽

Pranav Pandit ◽

Andrew G. McArthur ◽

Arinjay Banerjee ◽

Karen Mossman

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Evolutionary History ◽

Severe Disease ◽

Virus Transmission ◽

Virus Evolution ◽

Evolutionary Trajectory ◽

Independent Evolution ◽

Human Coronaviruses ◽

Novel Coronavirus ◽

Endemic Infections

AbstractThe emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more recently, the independent evolution of multiple SARS-CoV-2 variants has generated renewed interest in virus evolution and cross-species transmission. While all known human coronaviruses (HCoVs) are speculated to have originated in animals, very little is known about their evolutionary history and factors that enable some CoVs to co-exist with humans as low pathogenic and endemic infections (HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1), while others, such as SARS-CoV, MERS-CoV and SARS-CoV-2 have evolved to cause severe disease. In this review, we highlight the origins of all known HCoVs and map positively selected for mutations within HCoV proteins to discuss the evolutionary trajectory of SARS-CoV-2. Furthermore, we discuss emerging mutations within SARS-CoV-2 and variants of concern (VOC), along with highlighting the demonstrated or speculated impact of these mutations on virus transmission, pathogenicity, and neutralization by natural or vaccine-mediated immunity.

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Interviral Recombination between Plant, Insect, and Fungal RNA Viruses: Role of the Intracellular Ca2+/Mn2+ Pump

Journal of Virology ◽

10.1128/jvi.01015-19 ◽

2019 ◽

Vol 94 (1) ◽

Author(s):

Nikolay Kovalev ◽

Judit Pogany ◽

Peter D. Nagy

Keyword(s):

Driving Forces ◽

Rna Viruses ◽

Genetic Recombination ◽

Hot Spot ◽

Plant Viruses ◽

Template Switching ◽

Rna Recombination ◽

Content Type ◽

Intracellular Ca

ABSTRACT Recombination is one of the driving forces of viral evolution. RNA recombination events among similar RNA viruses are frequent, although RNA recombination could also take place among unrelated viruses. In this paper, we have established efficient interviral recombination systems based on yeast and plants. We show that diverse RNA viruses, including the plant viruses tomato bushy stunt virus, carnation Italian ringspot virus, and turnip crinkle virus-associated RNA; the insect plus-strand RNA [(+)RNA] viruses Flock House virus and Nodamura virus; and the double-stranded L-A virus of yeast, are involved in interviral recombination events. Most interviral recombinants are minus-strand recombinant RNAs, and the junction sites are not randomly distributed, but there are certain hot spot regions. Formation of interviral recombinants in yeast and plants is accelerated by depletion of the cellular SERCA-like Pmr1 ATPase-driven Ca2+/Mn2+ pump, regulating intracellular Ca2+ and Mn2+ influx into the Golgi apparatus from the cytosol. The interviral recombinants are generated by a template-switching mechanism during RNA replication by the viral replicase. Replication studies revealed that a group of interviral recombinants is replication competent in cell-free extracts, in yeast, and in the plant Nicotiana benthamiana. We propose that there are major differences among the viral replicases to generate and maintain interviral recombinants. Altogether, the obtained data promote the model that host factors greatly contribute to the formation of recombinants among related and unrelated viruses. This is the first time that a host factor’s role in affecting interviral recombination is established. IMPORTANCE Viruses with RNA genomes are abundant, and their genomic sequences show astonishing variation. Genetic recombination in RNA viruses is a major force behind their rapid evolution, enhanced pathogenesis, and adaptation to their hosts. We utilized a previously identified intracellular Ca2+/Mn2+ pump-deficient yeast to search for interviral recombinants. Noninfectious viral replication systems were used to avoid generating unwanted infectious interviral recombinants. Altogether, interviral RNA recombinants were observed between plant and insect viruses, and between a fungal double-stranded RNA (dsRNA) virus and an insect virus, in the yeast host. In addition, interviral recombinants between two plant virus replicon RNAs were identified in N. benthamiana plants, in which the intracellular Ca2+/Mn2+ pump was depleted. These findings underline the crucial role of the host in promoting RNA recombination among unrelated viruses.

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Human Coronaviruses: Counteracting the Damage by Storm

Viruses ◽

10.3390/v13081457 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1457

Author(s):

Dewald Schoeman ◽

Burtram C. Fielding

Keyword(s):

Immune Response ◽

Severe Disease ◽

Antiviral Agents ◽

The Elderly ◽

Highly Pathogenic ◽

Vaccine Responses ◽

Cell Mediated Immune Response ◽

Inhibition Antibody ◽

A Cell ◽

Human Coronaviruses

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

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491. Aerosol-Generating Medical Procedures: Transmission of SARS-CoV-2 and Emerging Viruses

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.684 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S312-S312

Author(s):

Seth D Judson ◽

Vincent J Munster

Keyword(s):

High Risk ◽

Severe Disease ◽

Experimental Studies ◽

Virus Transmission ◽

Nosocomial Transmission ◽

Medical Procedures ◽

Emerging Viruses ◽

Zoonotic Viruses ◽

Increased Risk ◽

Hospital Acquired

Abstract Background During the pandemic of coronavirus disease 2019 (COVID-19), many questions arose regarding risks for hospital-acquired or nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aerosol generating medical procedures (AGMPs), techniques that can generate infectious, virus-laden aerosols, could potentially amplify transmission among healthcare workers (HCWs). Thus, it was widely recommended that HCWs use airborne precautions when performing AGMPs. However, in clinical settings it is often unclear what procedures constitute AGMPs and how the risk varies by procedure or pathogen. We set out to further define AGMPs and assess the risk for nosocomial transmission of SARS-CoV-2 and other high-risk viruses via AGMPs. Methods We identified potential AGMPs and emerging viruses that were high-risk for nosocomial transmission through reviewing experimental and clinical data. Potential AGMPs were those associated with previous virus transmission or mechanically capable of transmission. High-risk viruses were defined as those that cause severe disease in humans for which limited therapies or interventions exist, are infectious via aerosols in humans or non-human primates (NHPs), found in the respiratory tract of infected humans or NHPs, and had previous evidence of nosocomial transmission. Results We identified multiple potential AGMPs, which could be divided into those that generate aerosols or induce a patient to form aerosols, as well as eight families of high-risk viruses. All of the viruses were emerging zoonotic RNA viruses. In the family Coronaviridae, we identified potential evidence for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 transmission via AGMPs. SARS-CoV-1 and SARS-CoV-2 were also found to be similarly stable when aerosolized. Conclusion Multiple emerging zoonotic viruses pose a high risk for nosocomial transmission through a variety of AGMPs. Given the similar stability of SARS-CoV-2 with SARS-CoV-1 when aerosolized and prior nosocomial transmission of SARS-CoV-1 via AGMPs, we suspect that certain AGMPs pose an increased risk for SARS-CoV-2 transmission. Additional experimental studies and on-site clinical sampling during AGMPs are necessary to further risk stratify AGMPs. Disclosures All Authors: No reported disclosures

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Changes in Antigen-Specific Cytokine and Chemokine Responses to Plasmodium falciparum Antigens in a Highland Area of Kenya after a Prolonged Absence of Malaria Exposure

Infection and Immunity ◽

10.1128/iai.01924-14 ◽

2014 ◽

Vol 82 (9) ◽

pp. 3775-3782 ◽

Cited By ~ 6

Author(s):

Lyticia A. Ochola ◽

Cyrus Ayieko ◽

Lily Kisia ◽

Ng'wena G. Magak ◽

Estela Shabani ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Severe Disease ◽

Clinical Malaria ◽

Necrosis Factor Alpha ◽

Content Type ◽

Highland Area ◽

Cytokine Responses ◽

Increased Risk ◽

Tnf Α ◽

Ifn Γ

ABSTRACTIndividuals naturally exposed toPlasmodium falciparumlose clinical immunity after a prolonged lack of exposure.P. falciparumantigen-specific cytokine responses have been associated with protection from clinical malaria, but the longevity ofP. falciparumantigen-specific cytokine responses in the absence of exposure is not well characterized. A highland area of Kenya with low and unstable malaria transmission provided an opportunity to study this question. The levels of antigen-specific cytokines and chemokines associated in previous studies with protection from clinical malaria (gamma interferon [IFN-γ], interleukin-10 [IL-10], and tumor necrosis factor alpha [TNF-α]), with increased risk of clinical malaria (IL-6), or with pathogenesis of severe disease in malaria (IL-5 and RANTES) were assessed by cytometric bead assay in April 2008, October 2008, and April 2009 in 100 children and adults. During the 1-year study period, none had an episode of clinicalP. falciparummalaria. Two patterns of cytokine responses emerged, with some variation by antigen: a decrease at 6 months (IFN-γ and IL-5) or at both 6 and 12 months (IL-10 and TNF-α) or no change over time (IL-6 and RANTES). These findings document thatP. falciparumantigen-specific cytokine responses associated in prior studies with protection from malaria (IFN-γ, TNF-α, and IL-10) decrease significantly in the absence ofP. falciparumexposure, whereas those associated with increased risk of malaria (IL-6) do not. The study findings provide a strong rationale for future studies of antigen-specific IFN-γ, TNF-α, and IL-10 responses as biomarkers of increased population-level susceptibility to malaria after prolonged lack ofP. falciparumexposure.

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Driving forces and structural changes of China as a market provider for Korea

Journal of Korea Trade ◽

10.1108/jkt-03-2018-0014 ◽

2018 ◽

Vol 22 (3) ◽

pp. 194-211 ◽

Cited By ~ 1

Author(s):

Yongqi Feng ◽

Tianshu Zhang

Keyword(s):

Steady State ◽

Driving Force ◽

Design Methodology ◽

Structural Changes ◽

Driving Forces ◽

Consumption Expenditure ◽

Input Output ◽

Content Type ◽

Fixed Capital Formation ◽

The Impact

Purpose The purpose of this paper is to provide a better understanding of the driving forces and structural changes of China as a market provider for Korea. This paper gives the answers for the following questions: How do China’s final demands trigger the growth of its imports from Korea? And what’s the impact of China’s final demands on the import in different industries? Design/methodology/approach Based on the Multi-Regional Input-Output model and World Input-Output Table database, this paper constructs the non-competitive imports input-output (IO) table of China to Korea. According to this table, we can calculate the induced imports coefficient and comprehensive induced import coefficients of China’s four final demands for imports from Korea in the 56 industries in China. Findings Among the four driving forces, the strongest one is changes in inventories and valuables. The impact of final consumption expenditure and fixed capital formation is much lower than that of changes in inventories and valuables, but they have a broader impact for the 56 industries. This paper finds out the China’s import induction of the final demands to Korea peaked in 2005 and 2010 and decreased greatly in 2014, so the position of China as market provider for Korea will no longer rise substantially, contrarily it will be in a steady state. Originality/value First, this paper constructs the non-competitive IO table to analyze the market provider issues between two countries and provides practical ways and methods for studies on the issues of imports and market provider. Second, this paper investigates the different roles of four final demands on driving force of China as market provider for Korea and the structural changes of China as a market provider for Korea among 56 industries from 2000 to 2014.

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Genotype and phenotypic spectrum of vitamin D dependent rickets type 1A: our experience and systematic review

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0403 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Manjunath Havalappa Dodamani ◽

Manjeetkaur Sehemby ◽

Saba Samad Memon ◽

Vijaya Sarathi ◽

Anurag R. Lila ◽

...

Keyword(s):

Systematic Review ◽

Vitamin D ◽

World Literature ◽

Hot Spot ◽

Severe Disease ◽

Delayed Diagnosis ◽

Hypophosphatemic Rickets ◽

Term Outcome ◽

Long Term Outcome ◽

Pathogenic Variants

Abstract Background Vitamin D dependent rickets type 1 (VDDR1) is a rare disease due to pathogenic variants in 1-α hydroxylase gene. We describe our experience with systematic review of world literature to describe phenotype and genotype. Methods Seven patients from six unrelated families with genetically proven VDDR1 from our cohort and 165 probands from systematic review were analyzed retrospectively. The clinical features, biochemistry, genetics, management, and long-term outcome were retrieved. Results In our cohort, the median age at presentation and diagnosis was 11(4–18) and 40(30–240) months. The delayed diagnoses were due to misdiagnoses as renal tubular acidosis and hypophosphatemic rickets. Four had hypocalcemic seizures in infancy whereas all had rickets by 2 years. All patients had biochemical response to calcitriol, however two patients diagnosed post-puberty had persistent deformity. Genetic analysis revealed two novel (p.Met260Arg, p.Arg453Leu) and a recurring variant (p.Phe443Profs*24). Systematic review showed that seizures as most common presentation in infancy, whereas delayed motor milestones and deformities after infancy. Diagnosis was delayed in 27 patients. Patients with unsatisfactory response despite compliance were >12 years at treatment initiation. Inappropriately normal 1,25(OH)2D may be present, however suppressed ratio of 1,25(OH)2 D/25(OH)D may provide a clue to diagnosis. Various region specific and hot-spot recurrent variants are described. Patients with truncating variants had higher daily calcitriol requirement and greatly suppressed ratio of 1,25(OH)2D/25(OH)D. Conclusion Delayed diagnosis may lead to permanent short stature and deformities. Truncating variants tend to have severe disease as compared to non-truncating variants. Diagnostic accuracy of 1,25(OH)2 D/25(OH)D ratio needs further validation.

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Future study of textile industry in Iran using the MICMAC and soft operational research methods

foresight ◽

10.1108/fs-02-2020-0017 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Mohammad Reza Fathi ◽

Seyed Mohammad Sobhani ◽

Mohammad Hasan Maleki ◽

Gholamreza Jandaghi

Keyword(s):

Research Methods ◽

Future Study ◽

Textile Industry ◽

Operational Research ◽

Driving Forces ◽

Business Environment ◽

Systems Methodology ◽

Content Type ◽

Delphi Approach ◽

Two Factors

Purpose This study aims to formulate exploratory scenarios of the textile industry in Iran based on MICMAC and soft operational research methods. Design/methodology/approach In this study, to formulate plausible scenarios, literature reviews and external experts’ opinions of this field have been gathered through the Delphi approach and uncertainty questionnaires. After the utilization of the most important uncertainties, the textile industry’s plausible scenarios have been mapped with the help of experts through co-thinking workshops. Results show that two factors, including the business atmosphere and membership in World Trade Organization (WTO), play a more important role than the other factors. These two factors were considered for the formulation of the scenario. To formulate plausible scenarios, soft systems methodology, which is a kind of soft operational research methods, is applied. Findings Based on the results, four scenarios are presented. These scenarios include the Elysium scenario, Hades scenario, Tatarus scenario and Sisyphus scenario. In the Elysium scenario, the business atmosphere has improved and Iran has been granted membership of the WTO. In Hades scenario, Iran has joined the WTO, but due to the government’s weakness and inactivity and key decision-makers, the required preparations have not been made. In the Tatarus scenario, Iran is not a WTO member and the business atmosphere is disastrous. In the Sisyphus scenario, the government takes reasonable actions toward a better business environment. Originality/value Formulating plausible scenarios of the textile industry is an excellent contribution to the key beneficiaries and actors of this industry so they can present flexible preparation-based programs in the face of circumstances. Future study of the textile industry familiarizes the actors and beneficiaries of this industry with the procedures and the driving forces that influence this industry’s future and it will ascertain various scenarios for the actors of this field.

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Kinome Expansion in theFusarium oxysporumSpecies Complex Driven by Accessory Chromosomes

mSphere ◽

10.1128/msphere.00231-18 ◽

2018 ◽

Vol 3 (3) ◽

Cited By ~ 5

Author(s):

Gregory A. DeIulio ◽

Li Guo ◽

Yong Zhang ◽

Jonathan M. Goldberg ◽

H. Corby Kistler ◽

...

Keyword(s):

Fusarium Oxysporum ◽

Species Complex ◽

Severe Disease ◽

Cellular Responses ◽

Human Pathogens ◽

Content Type ◽

Evolutionary Forces ◽

Environmental Signal ◽

Wide Range ◽

Opportunistic Fungal Pathogen

ABSTRACTTheFusarium oxysporumspecies complex (FOSC) is a group of soilborne pathogens causing severe disease in more than 100 plant hosts, while individual strains exhibit strong host specificity. Both chromosome transfer and comparative genomics experiments have demonstrated that lineage-specific (LS) chromosomes contribute to the host-specific pathogenicity. However, little is known about the functional importance of genes encoded in these LS chromosomes. Focusing on signaling transduction, this study compared the kinomes of 12F. oxysporumisolates, including both plant and human pathogens and 1 nonpathogenic biocontrol strain, with 7 additional publicly available ascomycete genomes. Overall,F. oxysporumkinomes are the largest, facilitated in part by the acquisitions of the LS chromosomes. The comparative study identified 99 kinases that are present in almost all examined fungal genomes, forming the core signaling network of ascomycete fungi. Compared to the conserved ascomycete kinome, the expansion of theF. oxysporumkinome occurs in several kinase families such as histidine kinases that are involved in environmental signal sensing and target of rapamycin (TOR) kinase that mediates cellular responses. Comparative kinome analysis suggests a convergent evolution that shapes individualF. oxysporumisolates with an enhanced and unique capacity for environmental perception and associated downstream responses.IMPORTANCEIsolates ofFusarium oxysporumare adapted to survive a wide range of host and nonhost conditions. In addition,F. oxysporumwas recently recognized as the top emerging opportunistic fungal pathogen infecting immunocompromised humans. The sensory and response networks of these fungi undoubtedly play a fundamental role in establishing the adaptability of this group. We have examined the kinomes of 12F. oxysporumisolates and highlighted kinase families that distinguishF. oxysporumfrom other fungi, as well as different isolates from one another. The amplification of kinases involved in environmental signal relay and regulating downstream cellular responses clearly setsFusariumapart from otherAscomycetes. Although the functions of many of these kinases are still unclear, their specific proliferation highlights them as a result of the evolutionary forces that have shaped this species complex and clearly marks them as targets for exploitation in order to combat disease.

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Histopathology ofBordetella pertussisin the Baboon Model

Infection and Immunity ◽

10.1128/iai.00511-18 ◽

2018 ◽

Vol 86 (11) ◽

Cited By ~ 5

Author(s):

Lindsey I. Zimmerman ◽

James F. Papin ◽

Jason Warfel ◽

Roman F. Wolf ◽

Stanley D. Kosanke ◽

...

Keyword(s):

Severe Disease ◽

Clinical Signs ◽

Human Infant ◽

Mucus Production ◽

Content Type ◽

Age Related ◽

Baboon Model ◽

Relevant Animal Model ◽

Significant Pathology ◽

Conducting Airways

ABSTRACTPertussis is a severe respiratory disease caused byBordetella pertussis. The classic symptoms of pertussis include paroxysmal coughing with an inspiratory whoop, posttussive vomiting, cyanosis, and persistent coryzal symptoms. Infants under 2 months of age experience more severe disease, with most deaths occurring in this age group. Most of what is known about the pathology of pertussis in humans is from the evaluation of fatal human infant cases. The baboon model of pertussis provides the opportunity to evaluate the histopathology of severe but nonfatal pertussis. The baboon model recapitulates the characteristic clinical signs of pertussis observed in humans, including leukocytosis, paroxysmal coughing, mucus production, heavy colonization of the airway, and transmission of the bacteria between hosts. As in humans, baboons demonstrate age-related differences in clinical presentation, with younger animals experiencing more severe disease. We examined the histopathology of 5- to 6-week-old baboons, with the findings being similar to those reported for fatal human infant cases. In juvenile baboons, we found that the disease is highly inflammatory and concentrated to the lungs with signs of disease that would typically be diagnosed as acute respiratory distress syndrome (ARDS) and bronchopneumonia. In contrast, no significant pathology was observed in the trachea. Histopathological changes in the trachea were limited to cellular infiltrates and mucus production. Immunohistostaining revealed that the bacteria were localized to the surface of the ciliated epithelium in the conducting airways. Our observations provide important insights into the pathology of pertussis in typical, severe but nonfatal pertussis cases in a very relevant animal model.

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