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The Journal of General Virology Feb 2024is a family of negative-sense RNA viruses with genomes of about 13.1-20.9 kb that infect fish, mammals and reptiles. The filovirid genome is a linear, non-segmented...
is a family of negative-sense RNA viruses with genomes of about 13.1-20.9 kb that infect fish, mammals and reptiles. The filovirid genome is a linear, non-segmented RNA with five canonical open reading frames (ORFs) that encode a nucleoprotein (NP), a polymerase cofactor (VP35), a glycoprotein (GP), a transcriptional activator (VP30) and a large protein (L) containing an RNA-directed RNA polymerase (RdRP) domain. All filovirid genomes encode additional proteins that vary among genera. Several filovirids (e.g., Ebola virus, Marburg virus) are pathogenic for humans and highly virulent. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family , which is available at www.ictv.global/report/filoviridae.
Topics: Animals; Humans; Ebolavirus; Rhabdoviridae; Phylogeny; Marburgvirus; Genome, Viral; Virus Replication; Mammals
PubMed: 38305775
DOI: 10.1099/jgv.0.001955 -
MSphere Aug 2023Canine distemper virus (CDV) causes systemic infection resulting in severe and often fatal disease in a large spectrum of animal host species. The virus is closely...
Canine distemper virus (CDV) causes systemic infection resulting in severe and often fatal disease in a large spectrum of animal host species. The virus is closely related to measles virus and targets myeloid, lymphoid, and epithelial cells, but CDV is more virulent and the infection spreads more rapidly within the infected host. Here, we aimed to study the pathogenesis of wild-type CDV infection by experimentally inoculating ferrets with recombinant CDV (rCDV) based on an isolate directly obtained from a naturally infected raccoon. The recombinant virus was engineered to express a fluorescent reporter protein, facilitating assessment of viral tropism and virulence. In ferrets, this wild type-based rCDV infected myeloid, lymphoid, and epithelial cells, and the infection resulted in systemic dissemination to multiple tissues and organs, especially those of the lymphatic system. High infection percentages in immune cells resulted in depletion of these cells both from circulation and from lymphoid tissues. The majority of CDV-infected ferrets reached their humane endpoints within 20 d and had to be euthanized. In that period, the virus also reached the central nervous system in several ferrets, but we did not observe the development of neurological complications during the study period of 23 d. Two out of 14 ferrets survived CDV infection and developed neutralizing antibodies. We show for the first time the pathogenesis of a non-adapted wild type-based rCDV in ferrets. IMPORTANCE Infection of ferrets with recombinant canine distemper virus (rCDV) expressing a fluorescent reporter protein has been used as proxy to understand measles pathogenesis and immune suppression in humans. CDV and measles virus use the same cellular receptors, but CDV is more virulent, and infection is often associated with neurological complications. rCDV strains in current use have complicated passage histories, which may have affected their pathogenesis. Here, we studied the pathogenesis of the first wild type-based rCDV in ferrets. We used macroscopic fluorescence to identify infected cells and tissues; multicolor flow cytometry to determine viral tropism in immune cells; and histopathology and immunohistochemistry to characterize infected cells and lesions in tissues. We conclude that CDV often overwhelmed the immune system, resulting in viral dissemination to multiple tissues in the absence of a detectable neutralizing antibody response. This virus is a promising tool to study the pathogenesis of morbillivirus infections.
Topics: Humans; Dogs; Animals; Distemper Virus, Canine; Ferrets; Distemper; Epithelial Cells; Measles virus; Antibodies, Neutralizing; Immune System
PubMed: 37377421
DOI: 10.1128/msphere.00082-23 -
Journal of Virology Nov 2023Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and regulates multiple cell developmental and signaling processes. It also functions as the cell entry...
Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and regulates multiple cell developmental and signaling processes. It also functions as the cell entry receptor for Nipah virus and Hendra virus, zoonotic viruses that can cause respiratory and/or neurological symptoms in humans with high mortality. Here, we investigate the sequence basis of EFNB2 specificity for binding the Nipah virus attachment G glycoprotein over Eph receptors. We then use this information to engineer EFNB2 as a soluble decoy receptor that specifically binds the attachment glycoproteins of the Nipah virus and other related henipaviruses to neutralize infection. These findings further mechanistic understanding of protein selectivity and may facilitate the development of diagnostics or therapeutics against henipavirus infection.
Topics: Humans; Ephrin-B2; Glycoproteins; Hendra Virus; Henipavirus Infections; Ligands; Nipah Virus; Viral Proteins
PubMed: 37931130
DOI: 10.1128/jvi.00621-23 -
Acta Biochimica Polonica Sep 2023The zoonotic pathogen, Nipah virus, is considered a potential healthcare threat due to its high mortality rates and detrimental symptoms like encephalitis. Ribavirin, an...
The zoonotic pathogen, Nipah virus, is considered a potential healthcare threat due to its high mortality rates and detrimental symptoms like encephalitis. Ribavirin, an antiviral drug helps in overcoming the number of casualties and reducing the mortality rate, but no long-lasting solution has been proposed yet putting global health security in jeopardy. Given the cognizance of mRNA-based vaccines as safe and efficacious preventative strategies against pathogens, the current study has utilized the reverse-vaccinology approach coupled with immunoinformatics to propose an mRNA-based vaccine candidate against the Nipah virus. To ensure the effectiveness of the vaccine candidate against all strains of Nipah and associated viruses, three fusion glycoproteins from Nipah and Hendra viruses were selected. A total of 30 potential epitopes, 10 B-cell-, 10 MHC-I-, and 10 MHC-II-specific, were screened for the construct. The finalized epitopes were highly antigenic with scores ranging from 0.75 to 1.7615 at a threshold of 0.4 for viruses and non-homologous to Homo sapiens eradicating any chance of immune tolerance. The construct, with a World population coverage of 97.2%, was structurally stable, thermostable, and hydrophilic with indices of 32.91, 93.62, and -0.002, respectively. The vaccine candidate's tertiary structure was predicted with a TM score of 0.131 and the refined model displayed superlative RAMA improvement (98.2) and MolProbity score (0.975). A quality factor of 93.5421% further validated the structural quality and stability. A prompt and stable immune response was also simulated, and the vaccine candidate was shown to eliminate from the body within the first five days of injection. Immune complexes count of 7000 mg/mL was predicted against the antigen with a small but nonsignificant danger signal, countered by the cytokines. Lastly, strong molecular interactions of the vaccine candidate with TLR-3 (331.09 kcal/mol) and TLR-4 (-333.31 kcal/mol) and molecular dynamics simulation analysis authenticated the immunogenic potential of the vaccine candidate. This vaccine candidate can serve as a foundation for future in-vitro and in-vivo trials to minimize or eradicate the diseases associated with the Nipah virus or the Henipaviral family.
Topics: Humans; Nipah Virus; Vaccinology; Glycoproteins; Epitopes; Immunity
PubMed: 37717262
DOI: 10.18388/abp.2020_6721 -
The Journal of Infectious Diseases Nov 2023Ebola virus (EBOV) is considered among the most dangerous viruses with case fatality rates approaching 90% depending on the outbreak. While several viral proteins (VPs)...
BACKGROUND
Ebola virus (EBOV) is considered among the most dangerous viruses with case fatality rates approaching 90% depending on the outbreak. While several viral proteins (VPs) including VP24, VP35, and the soluble glycoprotein are understood to contribute to virulence, less is known of the contribution of the highly variable mucin-like domain (MLD) of EBOV. Early studies have defined a potential role in immune evasion of the MLD by providing a glycan shield to critical glycoprotein residues tied to viral entry. Nonetheless, little is known as to what direct role the MLD plays in acute EBOV disease (EVD).
METHODS
We generated an infectious EBOV clone that lacks the MLD and assessed its virulence in ferrets compared with wild-type (WT) virus.
RESULTS
No differences in growth kinetics were observed in vitro, nor were there any differences in time to death, viremia, or clinical picture in ferrets infected with recombinant EBOV (rEBOV)-WT or rEBOV-Δmucin.
CONCLUSIONS
The EBOV MLD does not play a critical role in acute pathogenesis of EVD in ferrets.
Topics: Animals; Humans; Hemorrhagic Fever, Ebola; Mucins; Virulence; Ferrets; Ebolavirus; Glycoproteins
PubMed: 37379580
DOI: 10.1093/infdis/jiad240 -
Viruses Aug 2023The COVID-19 pandemic has had a significant impact on the epidemiology of respiratory viruses. Non-pharmaceutical interventions (NPIs) led to a dramatic reduction in...
BACKGROUND
The COVID-19 pandemic has had a significant impact on the epidemiology of respiratory viruses. Non-pharmaceutical interventions (NPIs) led to a dramatic reduction in respiratory infections. However, the long-term effects on respiratory virus epidemiology remain unclear.
MATERIALS AND METHODS
We conducted a comparative study on hospitalized pediatric patients with respiratory illness during two seasons: 1 October 2021 to 15 March 2022 and 1 October 2022 to 15 March 2023. We compared the type of virus, mean duration of hospitalization, and disease severity.
RESULTS
In the first season, 47.1% of patients (65/138) tested positive for at least one respiratory virus, with respiratory syncytial virus (RSV) being the most frequent (23.2%). In the second season, 82.9% of patients (102/123) tested positive, with RSV and being the most prevalent (28.38% and 27.03%, respectively). Other viruses, such as A/B, , and , also showed increased prevalence. Disease severity and mean duration of hospitalization were similar between the two seasons.
CONCLUSIONS
Our study highlights increased prevalence in respiratory viruses, including RSV and , following the easing of NPIs. The prevalence in respiratory viruses, including RSV and , increased in the second season compared to the first one. Interestingly, RSV's peak incidence shifted from February to November. The emergence of rhinovirus as the most prevalent respiratory virus during certain months suggests viral competition and dynamic changes in viral circulation. The overall severity of respiratory infections remained relatively stable between the seasons.
Topics: Humans; Child; Influenza, Human; Pandemics; Seasons; COVID-19; Rhinovirus; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Enterovirus Infections; Hospitalization
PubMed: 37766232
DOI: 10.3390/v15091825 -
BMC Infectious Diseases May 2024On 20 September 2022, Uganda declared its fifth Sudan virus disease (SVD) outbreak, culminating in 142 confirmed and 22 probable cases. The reproductive rate (R) of this...
BACKGROUND
On 20 September 2022, Uganda declared its fifth Sudan virus disease (SVD) outbreak, culminating in 142 confirmed and 22 probable cases. The reproductive rate (R) of this outbreak was 1.25. We described persons who were exposed to the virus, became infected, and they led to the infection of an unusually high number of cases during the outbreak.
METHODS
In this descriptive cross-sectional study, we defined a super-spreader person (SSP) as any person with real-time polymerase chain reaction (RT-PCR) confirmed SVD linked to the infection of ≥ 13 other persons (10-fold the outbreak R). We reviewed illness narratives for SSPs collected through interviews. Whole-genome sequencing was used to support epidemiologic linkages between cases.
RESULTS
Two SSPs (Patient A, a 33-year-old male, and Patient B, a 26-year-old male) were identified, and linked to the infection of one probable and 50 confirmed secondary cases. Both SSPs lived in the same parish and were likely infected by a single ill healthcare worker in early October while receiving healthcare. Both sought treatment at multiple health facilities, but neither was ever isolated at an Ebola Treatment Unit (ETU). In total, 18 secondary cases (17 confirmed, one probable), including three deaths (17%), were linked to Patient A; 33 secondary cases (all confirmed), including 14 (42%) deaths, were linked to Patient B. Secondary cases linked to Patient A included family members, neighbours, and contacts at health facilities, including healthcare workers. Those linked to Patient B included healthcare workers, friends, and family members who interacted with him throughout his illness, prayed over him while he was nearing death, or exhumed his body. Intensive community engagement and awareness-building were initiated based on narratives collected about patients A and B; 49 (96%) of the secondary cases were isolated in an ETU, a median of three days after onset. Only nine tertiary cases were linked to the 51 secondary cases. Sequencing suggested plausible direct transmission from the SSPs to 37 of 39 secondary cases with sequence data.
CONCLUSION
Extended time in the community while ill, social interactions, cross-district travel for treatment, and religious practices contributed to SVD super-spreading. Intensive community engagement and awareness may have reduced the number of tertiary infections. Intensive follow-up of contacts of case-patients may help reduce the impact of super-spreading events.
Topics: Humans; Uganda; Male; Cross-Sectional Studies; Adult; Disease Outbreaks; Female; Hemorrhagic Fever, Ebola; Whole Genome Sequencing; Ebolavirus
PubMed: 38783244
DOI: 10.1186/s12879-024-09391-0 -
Euro Surveillance : Bulletin Europeen... Dec 2023A monoclonal antibody for universal respiratory syncytial virus prophylaxis in infants has recently been licensed. We share our experiences of integrating nirsevimab...
Early lessons from the implementation of universal respiratory syncytial virus prophylaxis in infants with long-acting monoclonal antibodies, Galicia, Spain, September and October 2023.
A monoclonal antibody for universal respiratory syncytial virus prophylaxis in infants has recently been licensed. We share our experiences of integrating nirsevimab into the regional immunisation programme in Galicia, Spain. After a 3-week hospital-based immunisation campaign with flexible individualised appointments and educational activities, nirsevimab uptake was 97.5% in the high-risk group, 81.4% in the catch-up group and 92.6% in infants born during the campaign. This successful implementation strategy can serve as a model and may inform other countries' programmatic deliberations.
Topics: Infant; Humans; Antibodies, Monoclonal; Palivizumab; Respiratory Syncytial Virus Infections; Spain; Respiratory Syncytial Viruses; Antiviral Agents; Respiratory Syncytial Virus, Human
PubMed: 38062942
DOI: 10.2807/1560-7917.ES.2023.28.49.2300606 -
Emerging Microbes & Infections Dec 2023Taï Forest virus (TAFV) is a lesser-known ebolavirus that causes lethal infections in chimpanzees and is responsible for a single human case. Limited research has been...
Taï Forest virus (TAFV) is a lesser-known ebolavirus that causes lethal infections in chimpanzees and is responsible for a single human case. Limited research has been done on this human pathogen; however, with the recent emergence of filoviruses in West Africa, further investigation and countermeasure development against this virus is warranted. We developed a vesicular stomatitis virus (VSV)-based vaccine expressing the TAFV glycoprotein as the viral antigen and assessed it for protective efficacy in nonhuman primates (NHPs). Following a single high-dose vaccination, NHPs developed antigen-specific binding and neutralizing antibodies as well as modest T cell responses. Importantly, all vaccinated NHPs were uniformly protected from disease after lethal TAFV challenge while the naïve control group succumbed to the disease. Histopathologic lesions consistent with filovirus disease were present in control NHPs but were not observed in vaccinated NHPs. Transcriptional analysis of whole blood samples obtained after vaccination and challenge was performed to gain insight into molecular underpinnings conferring protection. Differentially expressed genes (DEG) detected 7 days post-vaccination were enriched to processes associated with innate immunity and antiviral responses. Only a small number of DEG was detected in vaccinated NHPs post-challenge while over 1,000 DEG were detected in control NHPs at end-stage disease which mapped to gene ontology terms indicative of defense responses and inflammation. Taken together, this data demonstrates the effective single-dose protection of the VSV-TAFV vaccine, and its potential for use in outbreaks.
Topics: Animals; Humans; Ebolavirus; Hemorrhagic Fever, Ebola; Macaca fascicularis; Viral Vaccines; Antibodies, Viral; Forests
PubMed: 37470396
DOI: 10.1080/22221751.2023.2239950 -
Journal of the Pediatric Infectious... Jul 2023Respiratory syncytial virus (RSV) contributes significantly to morbidity in children, placing substantial burdens on health systems, thus RSV vaccine development and...
BACKGROUND
Respiratory syncytial virus (RSV) contributes significantly to morbidity in children, placing substantial burdens on health systems, thus RSV vaccine development and program implementation are a public health priority. More data on burden are needed by policymakers to identify priority populations and formulate prevention strategies as vaccines are developed and licensed.
METHODS
Using health administrative data, we calculated incidence rates of RSV hospitalization in a population-based birth cohort of all children born over a six-year period (May 2009 to June 2015) in Ontario, Canada. Children were followed until their first RSV hospitalization, death, 5th birthday, or the end of the study period (June 2016). RSV hospitalizations were identified using a validated algorithm based on International Classification of Diseases, 10th Revision, and/or laboratory-confirmed outcomes. We calculated hospitalization rates by various characteristics of interest, including calendar month, age groups, sex, comorbidities, and gestational age.
RESULTS
The overall RSV hospitalization rate for children <5 years was 4.2 per 1000 person-years (PY) with a wide range across age groups (from 29.6 to 0.52 per 1000 PY in children aged 1 month and 36-59 months, respectively). Rates were higher in children born at a younger gestational age (23.2 per 1000 PY for those born at <28 weeks versus 3.9 per 1000 PY born at ≥37 weeks); this increased risk persisted as age increased. While the majority of children in our study had no comorbidities, rates were higher in children with comorbidities. For all age groups, rates were highest between December and March.
CONCLUSIONS
Our results confirm the high burden of RSV hospitalization and highlight young infants are at additional risk, namely premature infants. These results can inform prevention efforts.
Topics: Infant; Humans; Child; Incidence; Respiratory Syncytial Virus Infections; Ontario; Hospitalization; Respiratory Syncytial Virus, Human
PubMed: 37335754
DOI: 10.1093/jpids/piad045