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Cell Jul 2022Stem cell research endeavors to generate specific subtypes of classically defined "cell types." Here, we generate >90% pure human artery or vein endothelial cells from...
Stem cell research endeavors to generate specific subtypes of classically defined "cell types." Here, we generate >90% pure human artery or vein endothelial cells from pluripotent stem cells within 3-4 days. We specified artery cells by inhibiting vein-specifying signals and vice versa. These cells modeled viral infection of human vasculature by Nipah and Hendra viruses, which are extraordinarily deadly (∼57%-59% fatality rate) and require biosafety-level-4 containment. Generating pure populations of artery and vein cells highlighted that Nipah and Hendra viruses preferentially infected arteries; arteries expressed higher levels of their viral-entry receptor. Virally infected artery cells fused into syncytia containing up to 23 nuclei, which rapidly died. Despite infecting arteries and occupying ∼6%-17% of their transcriptome, Nipah and Hendra largely eluded innate immune detection, minimally eliciting interferon signaling. We thus efficiently generate artery and vein cells, introduce stem-cell-based toolkits for biosafety-level-4 virology, and explore the arterial tropism and cellular effects of Nipah and Hendra viruses.
Topics: Arteries; Endothelial Cells; Hendra Virus; Humans; Nipah Virus; Pluripotent Stem Cells; Tropism
PubMed: 35738284
DOI: 10.1016/j.cell.2022.05.024 -
Clinical Infectious Diseases : An... Aug 2022To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute... (Observational Study)
Observational Study
BACKGROUND
To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs).
METHODS
Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years.
RESULTS
Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012-2019, with changes ranging from -17.2% for RSV to -87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020-January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus.
CONCLUSIONS
Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children.
Topics: COVID-19; Child; Human bocavirus; Humans; Metapneumovirus; Orthomyxoviridae; Pandemics; Parainfluenza Virus 1, Human; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Virus Diseases; Viruses
PubMed: 34788811
DOI: 10.1093/cid/ciab942 -
Clinical Infectious Diseases : An... Jul 2022Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD)... (Meta-Analysis)
Meta-Analysis
Respiratory Syncytial Virus, Human Metapneumovirus, and Parainfluenza Virus Infections in Lung Transplant Recipients: A Systematic Review of Outcomes and Treatment Strategies.
BACKGROUND
Respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTR). This systematic review primarily aimed to assess outcomes of RSV/PIV/hMPV infections in LTR and secondarily to assess evidence regarding the efficacy of ribavirin.
METHODS
Relevant databases were queried and study outcomes extracted using a standardized method and summarized.
RESULTS
Nineteen retrospective and 12 prospective studies were included (total 1060 cases). Pooled 30-day mortality was low (0-3%), but CLAD progression 180-360 days postinfection was substantial (pooled incidences 19-24%) and probably associated with severe infection. Ribavirin trended toward effectiveness for CLAD prevention in exploratory meta-analysis (odds ratio [OR] 0.61, [0.27-1.18]), although results were highly variable between studies.
CONCLUSIONS
RSV/PIV/hMPV infection was followed by a high CLAD incidence. Treatment options, including ribavirin, are limited. There is an urgent need for high-quality studies to provide better treatment options for these infections.
Topics: Humans; Lung; Metapneumovirus; Parainfluenza Virus 1, Human; Parainfluenza Virus 2, Human; Paramyxoviridae Infections; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Retrospective Studies; Ribavirin; Transplant Recipients
PubMed: 35022697
DOI: 10.1093/cid/ciab969 -
International Journal of Clinical... Jan 2015On 23 March 2014, the World Health Organization first announced a new Ebola virus outbreak that started in December 2013 in the eastern part of the Republic of Guinea....
On 23 March 2014, the World Health Organization first announced a new Ebola virus outbreak that started in December 2013 in the eastern part of the Republic of Guinea. Human infections shortly emerged in Liberia, Sierra Leone, and Nigeria. On 30 September 2014, the Centers for Disease Control and Prevention confirmed through laboratory testing the first Ebola virus infection diagnosed in the USA, in a patient who travelled from West Africa to Texas. On 6 October 2014, the first human infection occurring outside of Africa was reported, in a Spanish nurse who treated two priests, both of whom died, and on 23 October 2014, the first human infection was reported in New York City. To date, the 2014 Ebola virus outbreak is the longest, largest, and most persistent one since 1976, when the virus was first identified in humans, and the number of human cases exceeded, as of mid-September 2014, the cumulative number of infections from all the previous outbreaks. The early clinical presentation overlaps with other infectious diseases, opening differential diagnosis difficulties. Understanding the transmission routes and identifying the natural reservoir of the virus are additional challenges in studying Ebola hemorrhagic fever outbreaks. Ebola virus is as much a public health challenge for developing countries as it is for the developed world, and previous outbreaks underscored that the relative contribution of the risk factors may differ among outbreaks. The implementation of effective preparedness plans is contingent on integrating teachings from previous Ebola virus outbreaks with those from the current outbreak and with lessons provided by other infectious diseases, along with developing a multifaceted inter-disciplinary and cross-disciplinary framework that should be established and shaped by biomedical as well as sociopolitical sciences.
Topics: Africa, Western; Disease Outbreaks; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Risk Factors; Travel
PubMed: 25496121
DOI: 10.1111/ijcp.12593 -
Advances in Experimental Medicine and... 2023The genus Henipavirus (HNV) includes two virulent infectious viruses, Nipah virus (NiV) and Hendra virus (HeV), which are the focus of considerable public health... (Review)
Review
The genus Henipavirus (HNV) includes two virulent infectious viruses, Nipah virus (NiV) and Hendra virus (HeV), which are the focus of considerable public health research efforts and have been classified as priority infectious diseases by the World Health Organization. Both viruses are high risk and should be handled in biosafety level 4 laboratories. Pseudotyped viruses containing the envelope proteins of HNV viruses have the same envelope protein structure as the authentic viruses; thus, they can mimic the receptor-binding and membrane fusion processes of authentic viruses with host cells and can be handled in biosafety level 2 laboratories. These characteristics enable pseudotyped viruses to be widely used in studies of viral infection mechanisms (packaging, budding, virus attachment, membrane fusion, viral entry, and glycosylation), inhibitory drug screening assays, and monoclonal antibody neutralization characteristics. This review will provide an overview of the progress of research concerning pseudotyped virus packaging systems for NiV and HeV.
Topics: Viral Envelope Proteins; Viral Pseudotyping; Hendra Virus; Nipah Virus; Virus Internalization
PubMed: 36920697
DOI: 10.1007/978-981-99-0113-5_9 -
Open Veterinary Journal 2022Paramyxoviruses have been shown to infect a wide range of hosts, including rodents, and humans. Several novel murine paramyxoviruses have been discovered in the last... (Review)
Review
Paramyxoviruses have been shown to infect a wide range of hosts, including rodents, and humans. Several novel murine paramyxoviruses have been discovered in the last several decades. Although these viruses are unclassified, they are recognized as Beilong virus, Mojiang virus (MojV), and Tailam virus in rats, Jeilongvirus, Nariva, Paju Apodemus paramyxovirus-1 and -2 in mice, and Pentlands paramyxovirus-1, -2, and -3 in squirrels. These paramyxoviruses were reported mainly in China and a few other countries like Australia, the Republic of Korea, Trinidad, and France. In June 2012, it becomes a great concern in China whereby, three miners were reported dead potentially caused by a novel zoonotic MojV, a henipa-like virus isolated from tissue samples of rats from the same cave. Rats are considered to be natural hosts for the MojV from the literature research. The classified paramyxovirus, Sendai virus in rodents is also reviewed. Paramyxoviruses infection in rodents leads to respiratory distress such as necrotizing rhinitis, tracheitis, bronchiolitis, and interstitial pneumonia. Infections caused by paramyxoviruses often spread between species, manifesting disease in spillover hosts, including humans. This review focuses on the paramyxoviruses in rodents, including the epidemiological distributions, transmission and pathogenesis, clinical manifestations, diagnostic methods, and control and prevention of paramyxoviruses infection to provide a better understanding of these highly mutating viruses.
Topics: Rats; Mice; Humans; Animals; Rodentia; Paramyxovirinae; Paramyxoviridae; Paramyxoviridae Infections
PubMed: 36650879
DOI: 10.5455/OVJ.2022.v12.i6.14 -
Viruses Dec 2018The order harbors numerous viruses of significant relevance to human health, including both established and emerging infections. Currently, vaccines are only available... (Review)
Review
The order harbors numerous viruses of significant relevance to human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses, and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread. Therefore, targeting cellular pathways used by viruses can provide novel therapeutic approaches. One of the key challenges confronted by both hosts and viruses alike is the successful folding and maturation of proteins. In cells, this task is faced by cellular molecular chaperones, a group of conserved and abundant proteins that oversee protein folding and help maintain protein homeostasis. In this review, we summarize the current knowledge of how the interact with cellular chaperones, highlight key gaps in our knowledge, and discuss the potential of chaperone inhibitors as antivirals.
Topics: Antiviral Agents; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Host-Pathogen Interactions; Humans; Measles virus; Molecular Chaperones; Mononegavirales; Protein Folding; Respiratory Syncytial Viruses; Virus Replication
PubMed: 30544818
DOI: 10.3390/v10120699 -
Frontiers in Immunology 2022Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable... (Review)
Review
Respiratory tract infections are a leading cause of morbidity and mortality in newborns, infants, and young children. These early life infections present a formidable immunologic challenge with a number of possibly conflicting goals: simultaneously eliminate the acute pathogen, preserve the primary gas-exchange function of the lung parenchyma in a developing lung, and limit long-term sequelae of both the infection and the inflammatory response. The latter has been most well studied in the context of childhood asthma, where multiple epidemiologic studies have linked early life viral infection with subsequent bronchospasm. This review will focus on the clinical relevance of respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and rhinovirus (RV) and examine the protective and pathogenic host responses within the neonate.
Topics: Child; Child, Preschool; Humans; Immunity; Infant; Infant, Newborn; Metapneumovirus; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Viruses
PubMed: 35493465
DOI: 10.3389/fimmu.2022.863149 -
Current Opinion in Pharmacology Oct 2021Over 40 filovirus disease outbreaks have been reported since the discovery of the first member of the Filoviridae family, and most of the outbreaks have occurred in... (Review)
Review
Over 40 filovirus disease outbreaks have been reported since the discovery of the first member of the Filoviridae family, and most of the outbreaks have occurred in Africa. In addition to deaths (primary impacts), there have also been health, social, economic, and political effects (secondary impacts) due to the outbreaks. Two large filovirus disease outbreaks have occurred in West and Central Africa in recent times, and direct and indirect repercussions resulting from the outbreaks underscores the need to strengthen the capacity of health services in disease hotspots.
Topics: Africa; Disease Outbreaks; Ebolavirus; Filoviridae; Hemorrhagic Fever, Ebola; Humans
PubMed: 34482213
DOI: 10.1016/j.coph.2021.07.016 -
Microscopy (Oxford, England) Jun 2023Filoviruses are filamentous enveloped viruses belonging to the family Filoviridae, in the order Mononegavirales. Some filovirus members, such as Ebola virus and Marburg... (Review)
Review
Filoviruses are filamentous enveloped viruses belonging to the family Filoviridae, in the order Mononegavirales. Some filovirus members, such as Ebola virus and Marburg virus, cause severe hemorrhagic fever in humans and non-human primates. The filovirus ribonucleoprotein complex, called the nucleocapsid, forms a double-layered helical structure in which a non-segmented, single-stranded, negative-sense RNA genome is encapsidated by the nucleoprotein (NP), viral protein 35 (VP35), VP24, VP30 and RNA-dependent RNA polymerase (L). The inner layer consists of the helical NP-RNA complex, acting as a scaffold for the binding of VP35 and VP24 that constitute the outer layer. Recent structural studies using cryo-electron microscopy have advanced our understanding of the molecular mechanism of filovirus nucleocapsid formation. Here, we review the key characteristics of the Ebola virus and Marburg virus nucleocapsid structures, highlighting the similarities and differences between the two viruses. In particular, we focus on the structure of the helical NP-RNA complex, the RNA binding mechanism and the NP-NP interactions in the helix. The structural analyses reveal a possible mechanism of nucleocapsid assembly and provide potential targets for the anti-filovirus drug design.
Topics: Animals; Cryoelectron Microscopy; Nucleocapsid; Ebolavirus; Marburgvirus; Viral Proteins; RNA
PubMed: 36242583
DOI: 10.1093/jmicro/dfac049