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Viruses May 2024A gene delivery system utilizing lentiviral vectors (LVs) requires high transduction efficiency for successful application in human gene therapy. Pseudotyping allows...
A gene delivery system utilizing lentiviral vectors (LVs) requires high transduction efficiency for successful application in human gene therapy. Pseudotyping allows viral tropism to be expanded, widening the usage of LVs. While vesicular stomatitis virus G (VSV-G) single-pseudotyped LVs are commonly used, dual-pseudotyping is less frequently employed because of its increased complexity. In this study, we examined the potential of phenotypically mixed heterologous dual-pseudotyped LVs with VSV-G and Sendai virus hemagglutinin-neuraminidase (SeV-HN) glycoproteins, termed V/HN-LV. Our findings demonstrated the significantly improved transduction efficiency of V/HN-LV in various cell lines of mice, cynomolgus monkeys, and humans compared with LV pseudotyped with VSV-G alone. Notably, V/HN-LV showed higher transduction efficiency in human cells, including hematopoietic stem cells. The efficient incorporation of wild-type SeV-HN into V/HN-LV depended on VSV-G. SeV-HN removed sialic acid from VSV-G, and the desialylation of VSV-G increased V/HN-LV infectivity. Furthermore, V/HN-LV acquired the ability to recognize sialic acid, particularly N-acetylneuraminic acid on the host cell, enhancing LV infectivity. Overall, VSV-G and SeV-HN synergistically improve LV transduction efficiency and broaden its tropism, indicating their potential use in gene delivery.
Topics: Animals; Humans; Genetic Vectors; Lentivirus; Sendai virus; Viral Envelope Proteins; Mice; Transduction, Genetic; HN Protein; Cell Line; Macaca fascicularis; Membrane Glycoproteins; Viral Tropism; HEK293 Cells; Gene Transfer Techniques; Genetic Therapy
PubMed: 38932120
DOI: 10.3390/v16060827 -
Viruses May 2024When designing live-attenuated respiratory syncytial virus (RSV) vaccine candidates, attenuating mutations can be developed through biologic selection or reverse-genetic...
When designing live-attenuated respiratory syncytial virus (RSV) vaccine candidates, attenuating mutations can be developed through biologic selection or reverse-genetic manipulation and may include point mutations, codon and gene deletions, and genome rearrangements. Attenuation typically involves the reduction in virus replication, due to direct effects on viral structural and replicative machinery or viral factors that antagonize host defense or cause disease. However, attenuation must balance reduced replication and immunogenic antigen expression. In the present study, we explored a new approach in order to discover attenuating mutations. Specifically, we used protein structure modeling and computational methods to identify amino acid substitutions in the RSV nonstructural protein 1 (NS1) predicted to cause various levels of structural perturbation. Twelve different mutations predicted to alter the NS1 protein structure were introduced into infectious virus and analyzed in cell culture for effects on viral mRNA and protein expression, interferon and cytokine expression, and caspase activation. We found the use of structure-based machine learning to predict amino acid substitutions that reduce the thermodynamic stability of NS1 resulted in various levels of loss of NS1 function, exemplified by effects including reduced multi-cycle viral replication in cells competent for type I interferon, reduced expression of viral mRNAs and proteins, and increased interferon and apoptosis responses.
Topics: Humans; Machine Learning; Viral Nonstructural Proteins; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Virus Replication; Vaccines, Attenuated; Respiratory Syncytial Virus Infections; Amino Acid Substitution; Mutation; Cell Line
PubMed: 38932114
DOI: 10.3390/v16060821 -
Communicable Diseases Intelligence... Jun 2024Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Little is known about the epidemiology, burden, and seasonality of RSV...
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Little is known about the epidemiology, burden, and seasonality of RSV in subtropical regions of Australia like Central Queensland. This information is important to plan prevention strategies, including therapeutics, future vaccines, and health system preparedness. We collected data on laboratory-confirmed RSV cases and admissions in Central Queensland for the period 1 July 2021 to 31 December 2022. From July 2021, RSV was listed as a nationally notifiable condition on laboratory-confirmed diagnosis. During the study period, 1,142 laboratory-confirmed cases of RSV (50.0% female sex) were reported, with 169 cases (14.8%) requiring hospital admission, 12 of which (7.1%) required intensive care unit/high dependency unit admissions; two deaths occurred. Of cases requiring hospital admission, RSV was listed as the primary diagnosis in 113/169 cases (66.9%); 63/169 admitted cases (37.3%) had a major comorbidity. Of all cases, 55.4% were in children < 5 years of age (20.9% hospitalised); 35.7% in children < 2 years of age (24.3% hospitalised), and 19.1% in children < 12 months of age (27.5% hospitalised). Children under five years of age made up 78.1% of admissions, a rate of 9.0 admissions per 1,000 children over the 18-month study period, with an average age of 15.8 months (standard deviation, SD: 13.1 months) in this cohort. Indigenous children aged < 5 years were over-represented in cases (rate ratio, RR: 1.6; 95% confidence interval [95% CI]: 1.3-1.9) and admissions (RR: 1.6; 95% CI: 1.0-2.4). Antibiotics were prescribed to 48.5% of admitted cases under two years of age, despite documented bacterial infection in only 26.3% of these cases; antibiotic prescription was significantly higher in those who received a chest X-ray (p < 0.001). Of all cases, 33.5% occurred in July 2022 alone, with greater than 75.0% of cases occurring during June-August 2022. RSV showed year-round activity with a distinctive winter peak in 2022; however, this season was likely affected by coronavirus disease 2019 (COVID-19) restrictions and behaviours. Ongoing surveillance is required to better understand the epidemiology and seasonality of RSV in Central Queensland.
Topics: Humans; Respiratory Syncytial Virus Infections; Queensland; Female; Male; Infant; Child, Preschool; Hospitalization; Respiratory Syncytial Virus, Human; Child; Seasons; Adolescent; Infant, Newborn; Adult; Middle Aged
PubMed: 38926651
DOI: 10.33321/cdi.2024.48.45 -
Expert Review of Molecular Diagnostics Jun 2024Nipah and Hendra viruses belong to the Paramyxoviridae family, which pose a significant threat to human health, with sporadic outbreaks causing severe morbidity and... (Review)
Review
INTRODUCTION
Nipah and Hendra viruses belong to the Paramyxoviridae family, which pose a significant threat to human health, with sporadic outbreaks causing severe morbidity and mortality. Early symptoms include fever, cough, sore throat, and headache, which offer little in terms of differential diagnosis. There are no specific therapeutics and vaccines for these viruses.
AREAS COVERED
This review comprehensively covers a spectrum of diagnostic techniques for Nipah and Hendra virus infections, discussed in conjunction with appropriate type of samples during the progression of infection. Serological assays, reverse transcriptase Real-Time PCR assays, and isothermal amplification assays are discussed in detail, along with a listing of few commercially available detection kits. Patents protecting inventions in Nipah and Hendra virus detection are also covered.
EXPERT OPINION
Despite several outbreaks of Nipah and Hendra infections in the past decade, in-depth research into their pathogenesis, Point-of-Care diagnostics, specific therapies, and human vaccines is lacking. A prompt and accurate diagnosis is pivotal for efficient outbreak management, patient treatment, and the adoption of preventative measures. The emergence of rapid point-of-care tests holds promise in enhancing diagnostic capabilities in real-world settings. The patent landscape emphasizes the importance of innovation and collaboration within the legal and business realms.
PubMed: 38924448
DOI: 10.1080/14737159.2024.2368591 -
Influenza and Other Respiratory Viruses Jun 2024Respiratory syncytial virus (RSV) and influenza infections cause significant annual morbidity and mortality worldwide in at-risk populations. This study is aimed at... (Comparative Study)
Comparative Study
BACKGROUND
Respiratory syncytial virus (RSV) and influenza infections cause significant annual morbidity and mortality worldwide in at-risk populations. This study is aimed at assessing hospital burden and healthcare resource utilization (HRU) of RSV and influenza in adults in Spain.
METHODS
Data were obtained from the Projected Hospitalisation Database of inpatient episodes (ages: younger adults 18-50 and 51-64 years; older adults 65-74, 75-84, and ≥ 85 years) during 2015, 2017, and 2018 in Spanish public hospitals. Incidence, mean hospitalization, and HRU assessments, including length of stay (LOS), intensive care unit (ICU) usage, and age-standardized mortality rates, were collected and stratified by age group, with analyses focusing on the adult population (≥ 18 years old).
RESULTS
Mean hospitalization rate in the population across all years was lower in individuals with RSV versus influenza (7.2/100,000 vs. 49.7/100,000 individuals). ICU admissions and median LOS were similar by age group for both viruses. Age-standardized mortality was 6.3/100,000 individuals and 6.1/100,000 individuals in patients with RSV and influenza, respectively, and mortality rates were similar in older adults (≥ 65 years) for both viruses.
CONCLUSIONS
RSV and influenza infection were associated with considerable HRU. There is a substantial disease burden for RSV infection in older adults ≥ 65 years. While RSV hospitalization rates in adults reported here appeared lower than influenza, RSV is still underdiagnosed in the hospital setting and its incidence might be similar to, or higher than, influenza.
Topics: Humans; Influenza, Human; Respiratory Syncytial Virus Infections; Middle Aged; Spain; Aged; Adult; Hospitalization; Young Adult; Adolescent; Aged, 80 and over; Male; Female; Incidence; Length of Stay; Cost of Illness; Respiratory Syncytial Virus, Human; Intensive Care Units
PubMed: 38923767
DOI: 10.1111/irv.13341 -
Avian Pathology : Journal of the W.V.P.A Jun 2024The within the family includes at least 22 different species, and is known to cause different types of infections and even be fatal in multiple avian species. There is...
The within the family includes at least 22 different species, and is known to cause different types of infections and even be fatal in multiple avian species. There is limited knowledge of the genetic and biological information of species -2 to 22 in domestic and wild birds and the disease significance of these viruses in birds is not fully determined, although as many as 10 new distinct species have been identified from wild birds and domestic poultry around the world in the last decade. This study aimed to use PCR, virus isolation, and sequencing to genetically and biologically characterize (AOAV-16) in wild birds and domestic poultry collected from different locations in China between 2014 and 2022. Of five isolated AOAV-16 strains (Y1 to Y5), only the Y4 strain had a hemagglutination (HA)-negative result. All of these isolates were low virulent viruses for chickens, except Y3 which was detected simultaneously with avian influenza virus (AIV) of H9N2 subtype. Furthermore, at least four different types of intergenic sequences (IGS) between the HN and L genes junction, and the recombination event as well as interspecific transmission by wild migratory birds, existed within the species AOAV-16. These findings and results of other reported AOAV-16 strains recommend strict control measures to limit contact between wild migratory birds and domestic poultry and imply potential threats to commercial poultry and even public health challenges worldwide.
PubMed: 38922304
DOI: 10.1080/03079457.2024.2373366 -
Virology Journal Jun 2024The genus Jeilongvirus comprises non-segmented negative-stranded RNA viruses that are classified within the Paramyxoviridae family by phylogeny. Jeilongviruses are found...
The genus Jeilongvirus comprises non-segmented negative-stranded RNA viruses that are classified within the Paramyxoviridae family by phylogeny. Jeilongviruses are found in various reservoirs, including rodents and bats. Rodents are typical viral reservoirs with diverse spectra and zoonotic potential. Little is currently known about jeilongviruses in rodents from central China. The study utilized high-throughput and Sanger sequencing to obtain jeilongvirus genomes, including those of two novel strains (HBJZ120/CHN/2021 (17,468 nt) and HBJZ157/CHN/2021 (19,143 nt)) and three known viruses (HBXN18/CHN/2021 (19,212 nt), HBJZ10/CHN/2021 (19,700 nt), HBJM106/CHN/2021 (18,871 nt)), which were characterized by genome structure, identity matrix, and phylogenetic analysis. Jeilongviruses were classified into three subclades based on their topology, phylogeny, and hosts. Based on the amino acid sequence identities and phylogenetic analysis of the L protein, HBJZ120/CHN/2021 and HBJZ157/CHN/2021 were found to be strains rather than novel species. Additionally, according to specific polymerase chain reaction screening, the positive percentage of Beilong virus in Hubei was 6.38%, suggesting that Beilong virus, belonging to the Jeilongvirus genus, is likely to be widespread in wild rodents. The identification of novel strains further elucidated the genomic diversity of jeilongviruses. Additionally, the prevalence of jeilongviruses in Hubei, China, was profiled, establishing a foundation for the surveillance and early warning of emerging paramyxoviruses.
Topics: Phylogeny; Animals; China; Genome, Viral; Rodentia; Animals, Wild; Paramyxovirinae; RNA, Viral; Paramyxoviridae Infections; High-Throughput Nucleotide Sequencing; Disease Reservoirs; Sequence Analysis, DNA
PubMed: 38918816
DOI: 10.1186/s12985-024-02417-8 -
BMC Infectious Diseases Jun 2024Annual epidemics of respiratory syncytial virus (RSV) had consistent timing and intensity between seasons prior to the SARS-CoV-2 pandemic (COVID-19). However, starting...
BACKGROUND
Annual epidemics of respiratory syncytial virus (RSV) had consistent timing and intensity between seasons prior to the SARS-CoV-2 pandemic (COVID-19). However, starting in April 2020, RSV seasonal activity declined due to COVID-19 non-pharmaceutical interventions (NPIs) before re-emerging after relaxation of NPIs. We described the unusual patterns of RSV epidemics that occurred in multiple subsequent waves following COVID-19 in different countries and explored factors associated with these patterns.
METHODS
Weekly cases of RSV from twenty-eight countries were obtained from the World Health Organisation and combined with data on country-level characteristics and the stringency of the COVID-19 response. Dynamic time warping and regression were used to cluster time series patterns and describe epidemic characteristics before and after COVID-19 pandemic, and identify related factors.
RESULTS
While the first wave of RSV epidemics following pandemic suppression exhibited unusual patterns, the second and third waves more closely resembled typical RSV patterns in many countries. Post-pandemic RSV patterns differed in their intensity and/or timing, with several broad patterns across the countries. The onset and peak timings of the first and second waves of RSV epidemics following COVID-19 suppression were earlier in the Southern than Northern Hemisphere. The second wave of RSV epidemics was also earlier with higher population density, and delayed if the intensity of the first wave was higher. More stringent NPIs were associated with lower RSV growth rate and intensity and a shorter gap between the first and second waves.
CONCLUSION
Patterns of RSV activity have largely returned to normal following successive waves in the post-pandemic era. Onset and peak timings of future epidemics following disruption of normal RSV dynamics need close monitoring to inform the delivery of preventive and control measures.
Topics: Humans; COVID-19; Respiratory Syncytial Virus Infections; SARS-CoV-2; Global Health; Seasons; Respiratory Syncytial Virus, Human; Pandemics
PubMed: 38918718
DOI: 10.1186/s12879-024-09509-4 -
Scientific Reports Jun 2024Nonpharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic have disrupted the dynamics of respiratory syncytial virus (RSV) on a global scale;...
Nonpharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic have disrupted the dynamics of respiratory syncytial virus (RSV) on a global scale; however, the cycling of RSV subtypes in the pre- and post-pandemic period remains poorly understood. Here, we used a two subtype RSV model supplemented with epidemiological data to study the impact of NPIs on the two circulating subtypes, RSV-A and RSV-B. The model is calibrated to historic RSV subtype data from the United Kingdom and Finland and predicts a tendency for RSV-A dominance over RSV-B immediately following the implementation of NPIs. Using a global genetic dataset, we confirm that RSV-A has prevailed over RSV-B in the post-pandemic period, consistent with a higher R for RSV-A. With new RSV infant monoclonals and maternal and elderly vaccines becoming widely available, these results may have important implications for understanding intervention effectiveness in the context of disrupted subtype dynamics.
Topics: Humans; COVID-19; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; United Kingdom; SARS-CoV-2; Finland; Infant; Pandemics
PubMed: 38914626
DOI: 10.1038/s41598-024-64624-1 -
Frontiers in Immunology 2024The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and...
The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous . These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic challenges.
Topics: Animals; Nipah Virus; Henipavirus Infections; Ferritins; Mesocricetus; Antibodies, Viral; Antibodies, Neutralizing; Nanoparticles; Viral Vaccines; Cricetinae; Vaccines, Virus-Like Particle; Female; Humans; Nanovaccines
PubMed: 38911870
DOI: 10.3389/fimmu.2024.1387811