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Annual Review of Pathology Jan 2017For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of... (Review)
Review
For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.
Topics: Disease Outbreaks; Ebolavirus; Hemorrhagic Fever, Ebola; Humans
PubMed: 27959626
DOI: 10.1146/annurev-pathol-052016-100506 -
International Journal of Biological... 2021Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune... (Review)
Review
Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. It has been more than 60 years since RSV was discovered, and the palivizumab monoclonal antibody, the only approved specific treatment, is limited to use for passive immunoprophylaxis in high-risk infants; no other intervention has been approved to date. However, in the past decade, substantial progress has been made in characterizing the structure and function of RSV components, their interactions with host surface molecules, and the host innate and adaptive immune response to infection. In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. A large number of promising monoclonal antibodies and inhibitors have been screened, and new vaccine candidates have been designed for clinical evaluation. In this review, we first briefly introduce the structural composition, host cell surface receptors and life cycle of RSV virions. Then, we discuss the latest findings related to the pathogenesis of RSV. We also focus on the latest clinical progress in the prevention and treatment of RSV infection through the development of monoclonal antibodies, vaccines and small-molecule inhibitors. Finally, we look forward to the prospects and challenges of future RSV research and clinical intervention.
Topics: Antiviral Agents; Genome, Viral; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Viral Vaccines
PubMed: 34671221
DOI: 10.7150/ijbs.64762 -
Presse Medicale (Paris, France : 1983) Sep 2022Measles is a highly contagious viral disease transmitted by aerosols through human-to-human contact. It is often considered as a benign disease, although mortality...
Measles is a highly contagious viral disease transmitted by aerosols through human-to-human contact. It is often considered as a benign disease, although mortality remains high in developing countries (>5%). Frequent complications (diarrhea, otitis, pneumonia, encephalitis) can be observed. The disease mainly affects young children from 5 to 6 months of age with a mortality peak in the first three years of life. The Persian physician Rhazes gave the first clinical description of the disease in the 10th century, clearly differentiating it from smallpox. Measles spread worldwide from the Renaissance. Its epidemiology was remarkably studied in 1846 by a Danish physician, Peter Panum, during an epidemic in the Faroe Islands. The viral nature of this disease was demonstrated in 1911 and the virus was identified in 1954 by Thomas Peebles and John Enders. It is a morbillivirus (family Paramyxoviridae), also responsible for rinderpest (ovine, bovine), distemper (canine, feline), and epidemic diseases of dolphins, porpoises and seals. The current measles virus appeared recently from the rinderpest virus around the 6th century BCE. It has adapted perfectly to the human species, becoming strictly human, without animal reservoirs. A live attenuated vaccine was developed in 1958 by Enders' team after numerous passages in cell cultures. The vaccine was licensed in the United States in 1963 and is used on a large scale by the WHO throughout the world. This highly effective and well-tolerated vaccine has greatly reduced the number of measles cases and saved millions of lives. Measles remains a major public health concern, causing over 100,000 deaths per year worldwide. Today, the most affected continents remain Africa, South America and Asia.
Topics: Child; Animals; Dogs; Cattle; Cats; Sheep; Humans; United States; Child, Preschool; Measles; Morbillivirus; Measles virus; Rinderpest virus; Asia
PubMed: 36414136
DOI: 10.1016/j.lpm.2022.104149 -
Annual Review of Virology Nov 2015The cultural impact of rabies, the fatal neurological disease caused by infection with rabies virus, registers throughout recorded history. Although rabies has been the... (Review)
Review
The cultural impact of rabies, the fatal neurological disease caused by infection with rabies virus, registers throughout recorded history. Although rabies has been the subject of large-scale public health interventions, chiefly through vaccination efforts, the disease continues to take the lives of about 40,000-70,000 people per year, roughly 40% of whom are children. Most of these deaths occur in resource-poor countries, where lack of infrastructure prevents timely reporting and postexposure prophylaxis and the ubiquity of domestic and wild animal hosts makes eradication unlikely. Moreover, although the disease is rarer than other human infections such as influenza, the prognosis following a bite from a rabid animal is poor: There is currently no effective treatment that will save the life of a symptomatic rabies patient. This review focuses on the major unanswered research questions related to rabies virus pathogenesis, especially those connecting the disease progression of rabies with the complex dysfunction caused by the virus in infected cells. The recent applications of cutting-edge research strategies to this question are described in detail.
Topics: Animals; Humans; Knowledge; Rabies; Rabies virus; Virulence
PubMed: 26958924
DOI: 10.1146/annurev-virology-100114-055157 -
Virology Journal Mar 2019Canine distemper virus (CDV), currently termed Canine morbillivirus, is an extremely contagious disease that affects dogs. It is identified as a multiple cell tropism... (Review)
Review
BACKGROUND
Canine distemper virus (CDV), currently termed Canine morbillivirus, is an extremely contagious disease that affects dogs. It is identified as a multiple cell tropism pathogen, and its host range includes a vast array of species. As a member of Mononegavirales, CDV has a negative, single-stranded RNA genome, which encodes eight proteins.
MAIN BODY
Regarding the molecular pathogenesis, the hemagglutinin protein (H) plays a crucial role both in the antigenic recognition and the viral interaction with SLAM and nectin-4, the host cells' receptors. These cellular receptors have been studied widely as CDV receptors in vitro in different cellular models. The SLAM receptor is located in lymphoid cells; therefore, the infection of these cells by CDV leads to immunosuppression, the severity of which can lead to variability in the clinical disease with the potential of secondary bacterial infection, up to and including the development of neurological signs in its later stage.
CONCLUSION
Improving the understanding of the CDV molecules implicated in the determination of infection, especially the H protein, can help to enhance the biochemical comprehension of the difference between a wide range of CDV variants, their tropism, and different steps in viral infection. The regions of interaction between the viral proteins and the identified host cell receptors have been elucidated to facilitate this understanding. Hence, this review describes the significant molecular and cellular characteristics of CDV that contribute to viral pathogenesis.
Topics: Animals; Disease Models, Animal; Distemper; Distemper Virus, Canine; Dogs; Hemagglutinins, Viral; Host Microbial Interactions; Host Specificity; Humans; Mice; Nectins; Receptors, Virus; Signaling Lymphocytic Activation Molecule Family Member 1; Viral Proteins; Viral Tropism; Zoonoses
PubMed: 30845967
DOI: 10.1186/s12985-019-1136-6 -
Viruses Sep 2023Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected... (Review)
Review
Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected with RSV by the age of two, and reinfections are common throughout life. Since antigenic variation, which is frequently observed among other respiratory viruses such as SARS-CoV-2 or influenza viruses, can only be observed for RSV to a limited extent, reinfections may result from short-term or incomplete immunity. After decades of research, two RSV vaccines were approved to prevent lower respiratory tract infections in older adults. Recently, the FDA approved a vaccine for active vaccination of pregnant women to prevent severe RSV disease in infants during their first RSV season. This review focuses on the host response to RSV infections mediated by epithelial cells as the first physical barrier, followed by responses of the innate and adaptive immune systems. We address possible RSV-mediated immunomodulatory and pathogenic mechanisms during infections and discuss the current vaccine candidates and alternative treatment options.
Topics: Infant; Child; Female; Pregnancy; Humans; Aged; Respiratory Syncytial Virus Infections; Reinfection; Respiratory Syncytial Viruses; Immunity; Vaccines; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 37896776
DOI: 10.3390/v15101999 -
EMBO Molecular Medicine Apr 2022In virology, the term seasonality describes variations in virus prevalence at more or less regular intervals throughout the year. Specifically, it has long been...
In virology, the term seasonality describes variations in virus prevalence at more or less regular intervals throughout the year. Specifically, it has long been recognized that outbreaks of human influenza viruses, respiratory syncytial virus (RSV), and human coronaviruses occur in temperate climates during the winter season, whereas low activity is detected during the summer months. Other human respiratory viruses, such as parainfluenza viruses, human metapneumoviruses, and rhinoviruses, show highest activity during the spring or fall season in temperate regions, depending on the virus and subtype. In tropical climates, influenza viruses circulate throughout the year and no distinct seasonal patterns are observed, although virus outbreaks tend to spike during the rainy season. Overall, seasonality is more pronounced with greater distance from the equator, and tends to be less pronounced in regions closer to the equator (Li et al, 2019).
Topics: Humans; Influenza, Human; Metapneumovirus; Orthomyxoviridae; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Viruses
PubMed: 35157360
DOI: 10.15252/emmm.202115352 -
Journal of Virology Oct 2020, known as nonsegmented negative-sense (NNS) RNA viruses, are a class of pathogenic and sometimes deadly viruses that include rabies virus (RABV), human respiratory... (Review)
Review
, known as nonsegmented negative-sense (NNS) RNA viruses, are a class of pathogenic and sometimes deadly viruses that include rabies virus (RABV), human respiratory syncytial virus (HRSV), and Ebola virus (EBOV). Unfortunately, no effective vaccines and antiviral therapeutics against many are currently available. Viral polymerases have been attractive and major antiviral therapeutic targets. Therefore, polymerases have been extensively investigated for their structures and functions. mimic RNA synthesis of their eukaryotic counterparts by utilizing multifunctional RNA polymerases to replicate entire viral genomes and transcribe viral mRNAs from individual viral genes as well as synthesize 5' methylated cap and 3' poly(A) tail of the transcribed viral mRNAs. The catalytic subunit large protein (L) and cofactor phosphoprotein (P) constitute the polymerases. In this review, we discuss the shared and unique features of RNA synthesis, the monomeric multifunctional enzyme L, and the oligomeric multimodular adapter P of We outline the structural analyses of the polymerases since the first structure of the vesicular stomatitis virus (VSV) L protein determined in 2015 and highlight multiple high-resolution cryo-electron microscopy (cryo-EM) structures of the polymerases of , namely, VSV, RABV, HRSV, human metapneumovirus (HMPV), and human parainfluenza virus (HPIV), that have been reported in recent months (2019 to 2020). We compare the structures of those polymerases grouped by virus family, illustrate the similarities and differences among those polymerases, and reveal the potential RNA synthesis mechanisms and models of highly conserved We conclude by the discussion of remaining questions, evolutionary perspectives, and future directions.
Topics: Animals; Cryoelectron Microscopy; Humans; Metapneumovirus; Models, Molecular; Mononegavirales; Protein Conformation; RNA, Messenger; RNA, Viral; RNA-Dependent RNA Polymerase; Rabies virus; Respiratory Syncytial Virus, Human; Vesicular stomatitis Indiana virus; Viral Proteins; Virus Replication
PubMed: 32847861
DOI: 10.1128/JVI.00175-20 -
Science (New York, N.Y.) Jan 2022The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat...
The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat to pediatric patients and older adults. We describe 4′-fluorouridine (4′-FlU, EIDD-2749), a ribonucleoside analog that inhibits RSV, related RNA viruses, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with high selectivity index in cells and human airway epithelia organoids. Polymerase inhibition within in vitro RNA-dependent RNA polymerase assays established for RSV and SARS-CoV-2 revealed transcriptional stalling after incorporation. Once-daily oral treatment was highly efficacious at 5 milligrams per kilogram (mg/kg) in RSV-infected mice or 20 mg/kg in ferrets infected with different SARS-CoV-2 variants of concern, initiated 24 or 12 hours after infection, respectively. These properties define 4′-FlU as a broad-spectrum candidate for the treatment of RSV, SARS-CoV-2, and related RNA virus infections.
Topics: Administration, Oral; Animals; Antiviral Agents; COVID-19; Cell Line; Coronavirus RNA-Dependent RNA Polymerase; Disease Models, Animal; Female; Ferrets; Humans; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mononegavirales; RNA-Dependent RNA Polymerase; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; SARS-CoV-2; Transcription, Genetic; Uracil Nucleotides; Virus Replication; COVID-19 Drug Treatment
PubMed: 34855509
DOI: 10.1126/science.abj5508 -
The Veterinary Clinics of North... Apr 2023Vesicular stomatitis (VS) is a vector-borne livestock disease caused by vesicular stomatitis New Jersey virus (VSNJV) or vesicular stomatitis Indiana virus (VSIV). The... (Review)
Review
Vesicular stomatitis (VS) is a vector-borne livestock disease caused by vesicular stomatitis New Jersey virus (VSNJV) or vesicular stomatitis Indiana virus (VSIV). The disease circulates endemically in northern South America, Central America, and Mexico and only occasionally causes outbreaks in the United States. Over the past 20 years, VS outbreaks in the southwestern and Rocky Mountain regions occurred periodically with incursion years followed by virus overwintering and subsequent expansion outbreak years. The regulatory response by animal health officials prevents the spread of disease by animals with lesions and manages trade impacts. Recent US outbreaks highlight potential climate change impacts on insect vectors or other transmission-related variables.
Topics: Horses; United States; Animals; Vesicular stomatitis Indiana virus; Vesicular Stomatitis; Horse Diseases; Vesiculovirus; Vesicular stomatitis New Jersey virus
PubMed: 36737291
DOI: 10.1016/j.cveq.2022.11.004