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Nature Communications May 2024The viral polymerase complex, comprising the large protein (L) and phosphoprotein (P), is crucial for both genome replication and transcription in non-segmented...
The viral polymerase complex, comprising the large protein (L) and phosphoprotein (P), is crucial for both genome replication and transcription in non-segmented negative-strand RNA viruses (nsNSVs), while structures corresponding to these activities remain obscure. Here, we resolved two L-P complex conformations from the mumps virus (MuV), a typical member of nsNSVs, via cryogenic-electron microscopy. One conformation presents all five domains of L forming a continuous RNA tunnel to the methyltransferase domain (MTase), preferably as a transcription state. The other conformation has the appendage averaged out, which is inaccessible to MTase. In both conformations, parallel P tetramers are revealed around MuV L, which, together with structures of other nsNSVs, demonstrates the diverse origins of the L-binding X domain of P. Our study links varying structures of nsNSV polymerase complexes with genome replication and transcription and points to a sliding model for polymerase complexes to advance along the RNA templates.
Topics: Cryoelectron Microscopy; Mumps virus; Viral Proteins; Models, Molecular; RNA, Viral; DNA-Directed RNA Polymerases; Protein Domains; Phosphoproteins; RNA-Dependent RNA Polymerase; Virus Replication; Transcription, Genetic; Protein Conformation
PubMed: 38760379
DOI: 10.1038/s41467-024-48389-9 -
Frontiers in Pediatrics 2024Pretransplant vaccination is generally recommended to solid organ transplant recipients. In infants with congenital nephrotic syndrome (CNS), the immune response is...
BACKGROUND
Pretransplant vaccination is generally recommended to solid organ transplant recipients. In infants with congenital nephrotic syndrome (CNS), the immune response is hypothetically inferior to other patients due to young age and urinary loss of immunoglobulins, but data on the immunization response in severely nephrotic children remain scarce. If effective, however, early immunization of infants with CNS would clinically be advantageous.
METHODS
We investigated serological vaccine responses in seven children with CNS who were immunized during nephrosis. Antibody responses to measles-mumps-rubella -vaccine (MMR), a pentavalent DTaP-IPV-Hib -vaccine (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, type b), varicella vaccine, combined hepatitis A and B vaccine, and pneumococcal conjugate vaccine (PCV) were measured after nephrectomy either before or after kidney transplantation.
RESULTS
Immunizations were started at a median age of 7 months [interquartile range (IQR) 7-8], with a concurrent median proteinuria of 36,500 mg/L (IQR 30,900-64,250). Bilateral nephrectomy was performed at a median age of 20 months (IQR 14-25), and kidney transplantation 10-88 days after the nephrectomy. Antibody levels were measured at median 18 months (IQR 6-23) after immunization. Protective antibody levels were detected in all examined children for hepatitis B (5/5), (7/7), rubella virus (2/2), and mumps virus (1/1); in 5/6 children for varicella; in 4/6 for poliovirus and vaccine-type pneumococcal serotypes; in 4/7 for type B and ; in 1/2 for measles virus; and in 2/5 for hepatitis A. None of the seven children had protective IgG levels against .
CONCLUSION
Immunization during severe congenital proteinuria resulted in variable serological responses, with both vaccine- and patient-related differences. Nephrosis appears not to be a barrier to successful immunization.
PubMed: 38756974
DOI: 10.3389/fped.2024.1392873 -
Vaccine: X Jun 2024Information regarding the detection perioid of measles vaccine virus (MeVV) RNA in human nasopharyngeal samples and measles-specific antibodies following...
Information regarding the detection perioid of measles vaccine virus (MeVV) RNA in human nasopharyngeal samples and measles-specific antibodies following measles-mumps-rubella (MMR) vaccination is limited. During contact tracing for a measles outbreak at a hospital in Republic of Korea, 4 out of 206 children vaccinated with MMR underwent real-time RT-PCR assay for measles and measles-specific antibodies test. Measles virus RNA was detected in 2 children, all of which was vaccine virus strain RNA (genotype A). In a healthy 27-month-old boy, MeVV RNA was detected 448 days after MMR vaccination. Measles-specific IgM was positive 1097 days following vaccination in a 4-year-old girl. MeVV RNA and measles-specific IgM were detected for a considerable period following primary MMR vaccination. Physicians should exercise caution when interpreting positive RT-PCR results for MeVV or measles-specific IgM from a child with measles-associated symptoms who has been recently vaccinated against measles.
PubMed: 38746062
DOI: 10.1016/j.jvacx.2024.100491 -
Journal of Public Health Research Apr 2024During the mumps outbreak in Japan in 2016, 159,031 cases were reported. In a survey conducted in 2015, mumps vaccination rates for the first dose were 30%-40%. However,...
BACKGROUND
During the mumps outbreak in Japan in 2016, 159,031 cases were reported. In a survey conducted in 2015, mumps vaccination rates for the first dose were 30%-40%. However, the rates for two or more doses were not determined. We assessed the mumps vaccination rates and mumps infection prevalence according to vaccine doses received.
DESIGN AND METHODS
This was a multicenter cross-sectional study. Students from three universities participated in 2019. Informed consent was obtained from the students and their guardians. The primary outcome was the prevalence of breakthrough mumps infection according to the number of doses of vaccine received. We collected data on past illnesses of vaccine-preventable diseases and vaccination history using a questionnaire, photocopies of the Maternal and Child Health Handbook from the guardians, and virus antibody titers from the universities' health centers.
RESULTS
This study assessed 2004 eligible students and included 593 (29.6%); of these, 250 (42.7%) had a mumps infection history. Furthermore, 264 (44.6%), 31 (5.2%), and 2 (0.3%) students received the first, second, and third doses of mumps vaccine, respectively. The mumps seropositivity prevalence was 43.2% ( = 127), 36.7% ( = 97), 26.7% ( = 8), and 100% ( = 2) for the no-, first-, second-, and third-dose groups, respectively ( for trend = 0.09). The mumps infection prevalence rates were 69.8% ( = 203), 11.3% ( = 28), 3.9% ( = 1), and 0% for the no-, first-, second-, and third-dose groups, respectively.
CONCLUSIONS
Approximately 1 in 10 students who had received only one dose of mumps-containing vaccine had a breakthrough infection history.
PubMed: 38694450
DOI: 10.1177/22799036241246702 -
BMC Infectious Diseases Apr 2024Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human...
Gut microbial features may influence antiviral IgG levels after vaccination against viral respiratory infectious diseases: the evidence from two-sample bidirectional mendelian randomization.
BACKGROUND
Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels.
METHODS
We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses.
RESULTS
The MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features.
CONCLUSIONS
The human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.
Topics: Humans; Immunoglobulin G; Mendelian Randomization Analysis; Gastrointestinal Microbiome; Respiratory Tract Infections; Genome-Wide Association Study; Antibodies, Viral; Vaccination; Virus Diseases
PubMed: 38654203
DOI: 10.1186/s12879-024-09189-0 -
Frontiers in Immunology 2024B cell transcriptomic signatures hold promise for the early prediction of vaccine-induced humoral immunity and vaccine protective efficacy. We performed a longitudinal...
B cell transcriptomic signatures hold promise for the early prediction of vaccine-induced humoral immunity and vaccine protective efficacy. We performed a longitudinal study in 232 healthy adult participants before/after a 3 dose of MMR (MMR3) vaccine. We assessed baseline and early transcriptional patterns in purified B cells and their association with measles-specific humoral immunity after MMR vaccination using two analytical methods ("per gene" linear models and joint analysis). Our study identified distinct early transcriptional signatures/genes following MMR3 that were associated with measles-specific neutralizing antibody titer and/or binding antibody titer. The most significant genes included: the interleukin 20 receptor subunit beta/ gene (a subunit receptor for IL-24, a cytokine involved in the germinal center B cell maturation/response); the phorbol-12-myristate-13-acetate-induced protein 1/, the brain expressed X-linked 2/ gene and the B cell Fas apoptotic inhibitory molecule/, involved in the selection of high-affinity B cell clones and apoptosis/regulation of apoptosis; as well as (encoding the B lymphocyte-derived IL-16 ligand of CD4), involved in the crosstalk between B cells, dendritic cells and helper T cells. Significantly enriched pathways included B cell signaling, apoptosis/regulation of apoptosis, metabolic pathways, cell cycle-related pathways, and pathways associated with viral infections, among others. In conclusion, our study identified genes/pathways linked to antigen-induced B cell proliferation, differentiation, apoptosis, and clonal selection, that are associated with, and impact measles virus-specific humoral immunity after MMR vaccination.
Topics: Adult; Humans; Measles-Mumps-Rubella Vaccine; Immunity, Humoral; Longitudinal Studies; Antibodies, Viral; Measles; Gene Expression Profiling; Nerve Tissue Proteins
PubMed: 38633249
DOI: 10.3389/fimmu.2024.1358477 -
Microbiology Spectrum May 2024Paramyxo- and filovirus genomes are equipped with bipartite promoters at their 3 ends to initiate RNA synthesis. The two elements, the primary promoter element 1 (PE1)...
UNLABELLED
Paramyxo- and filovirus genomes are equipped with bipartite promoters at their 3 ends to initiate RNA synthesis. The two elements, the primary promoter element 1 (PE1) and the secondary promoter element 2 (PE2), are separated by a spacer region that must be precisely a multiple of 6 nucleotides (nts), indicating these viruses adhere to the "rule of six." However, our knowledge of PE2 has been limited to a narrow spectrum of virus species. In this study, a comparative analysis of 1,647 paramyxoviral genomes from a public database revealed that the paramyxovirus PE2 can be clearly categorized into two distinct subcategories: one marked by C repeats at every six bases (exclusive to the subfamily ) and another characterized by CG repeats every 6 nts (observed in the subfamilies and ). This unique pattern collectively mirrors the evolutionary lineage of these subfamilies. Furthermore, we showed that PE2 of the , with the exception of mumps virus, serves as part of the gene-coding region. This may be due to the fact that the are the only paramyxoviruses that cannot propagate without RNA editing. Filoviruses have three to eight consecutive uracil repeats every six bases (UN) in PE2, which is located in the 3 end region of the genome. We obtained PE2 sequences from 2,195 filoviruses in a public database and analyzed the sequence conservation among virus species. Our results indicate that the continuity of UN hexamers is consistently maintained with a high degree of conservation across virus species.
IMPORTANCE
The genomic intricacies of paramyxo- and filoviruses are highlighted by the bipartite promoters-promoter element 1 (PE1) and promoter element 2 (PE2)-at their 3 termini. The spacer region between these elements follows the "rule of six," crucial for genome replication. By a comprehensive analysis of paramyxoviral genome sequences, we identified distinct subcategories of PE2 based on C and CG repeats that were specific to and /, respectively, mirroring their evolutionary lineages. Notably, the PE2 of is integrated into the gene-coding region, a unique trait potentially linked to its strict dependence on RNA editing for virus growth. This study also focused on the PE2 sequences in filovirus genomes. The strict conservation of the continuity of UN among virus species emphasizes its crucial role in viral genome replication.
Topics: Promoter Regions, Genetic; Phylogeny; Genome, Viral; Filoviridae; Paramyxoviridae; Humans; RNA, Viral; Evolution, Molecular; Animals
PubMed: 38606982
DOI: 10.1128/spectrum.00417-24 -
MMWR. Morbidity and Mortality Weekly... Apr 2024Measles is a highly infectious febrile rash illness and was declared eliminated in the United States in 2000. However, measles importations continue to occur, and U.S....
Measles is a highly infectious febrile rash illness and was declared eliminated in the United States in 2000. However, measles importations continue to occur, and U.S. measles elimination status was threatened in 2019 as the result of two prolonged outbreaks among undervaccinated communities in New York and New York City. To assess U.S. measles elimination status after the 2019 outbreaks and to provide context to understand more recent increases in measles cases, CDC analyzed epidemiologic and laboratory surveillance data and the performance of the U.S. measles surveillance system after these outbreaks. During January 1, 2020-March 28, 2024, CDC was notified of 338 confirmed measles cases; 97 (29%) of these cases occurred during the first quarter of 2024, representing a more than seventeenfold increase over the mean number of cases reported during the first quarter of 2020-2023. Among the 338 reported cases, the median patient age was 3 years (range = 0-64 years); 309 (91%) patients were unvaccinated or had unknown vaccination status, and 336 case investigations included information on ≥80% of critical surveillance indicators. During 2020-2023, the longest transmission chain lasted 63 days. As of the end of 2023, because of the absence of sustained measles virus transmission for 12 consecutive months in the presence of a well-performing surveillance system, U.S. measles elimination status was maintained. Risk for widespread U.S. measles transmission remains low because of high population immunity. However, because of the increase in cases during the first quarter of 2024, additional activities are needed to increase U.S. routine measles, mumps, and rubella vaccination coverage, especially among close-knit and undervaccinated communities. These activities include encouraging vaccination before international travel and rapidly investigating suspected measles cases.
Topics: United States; Humans; Infant; Infant, Newborn; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Measles; Measles virus; Vaccination; Vaccination Coverage; Disease Outbreaks; New York City; Measles-Mumps-Rubella Vaccine
PubMed: 38602886
DOI: 10.15585/mmwr.mm7314a1 -
Indian Pediatrics Apr 2024Mumps is a global public health problem caused by mumps virus, a member of paramyxoviridae family. MMR (Mumps, Measles, Rubella), an effective vaccine, has been... (Review)
Review
Mumps is a global public health problem caused by mumps virus, a member of paramyxoviridae family. MMR (Mumps, Measles, Rubella), an effective vaccine, has been incorporated into routine immunization schedules in over 100 countries. On the contrary, in India, vaccine against mumps has not been included in the routine immunization schedule as mumps is still not viewed as a significant public health problem by the government to warrant such an intervention. An increasing number of mumps outbreaks being reported from many parts of the country in the recent past, is matter of concern. The current paper reviews the situation of mumps in India including the recent surge, and discusses the remedial measures to contain these outbreaks. We conclude that inclusion of Mumps component as MMR vaccine in the Universal Immunization Programme of India along with strengthening surveillance is required to tackle the situation.
Topics: Humans; Antibodies, Viral; India; Measles; Measles-Mumps-Rubella Vaccine; Mumps; Rubella
PubMed: 38597102
DOI: No ID Found -
BioRxiv : the Preprint Server For... Mar 2024Immunoglobulin (IGH, IGK, IGL) loci in the human genome are highly polymorphic regions that encode the building blocks of the light and heavy chain IG proteins that...
Immunoglobulin (IGH, IGK, IGL) loci in the human genome are highly polymorphic regions that encode the building blocks of the light and heavy chain IG proteins that dimerize to form antibodies. The processes of V(D)J recombination and somatic hypermutation in B cells are responsible for creating an enormous reservoir of highly specific antibodies capable of binding a vast array of possible antigens. However, the antibody repertoire is fundamentally limited by the set of variable (V), diversity (D), and joining (J) alleles present in the germline IG loci. To better understand how the germline IG haplotypes contribute to the expressed antibody repertoire, we combined genome sequencing of the germline IG loci with single-cell transcriptome sequencing of B cells from the same donor. Sequencing and assembly of the germline IG loci captured the IGH locus in a single fully-phased contig where the maternal and paternal contributions to the germline V, D, and J repertoire can be fully resolved. The B cells were collected following a measles, mumps, and rubella (MMR) vaccination, resulting in a population of cells that were activated in response to this specific immune challenge. Single-cell, full-length transcriptome sequencing of these B cells resulted in whole transcriptome characterization of each cell, as well as highly-accurate consensus sequences for the somatically rearranged and hypermutated light and heavy chain IG transcripts. A subset of antibodies synthesized based on their consensus heavy and light chain transcript sequences demonstrated binding to measles antigens and neutralization of measles live virus.
PubMed: 38585716
DOI: 10.1101/2024.03.26.586834