Prevalence and Evolution of Noroviruses between 1966 and 2019, Implications for Vaccine Design.
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ABSTRACT:
SUBMITTER: Zhou HL
PROVIDER: S-EPMC8400007 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prompted by the discovery of new gastrointestinal viruses, the NIH, NIAID and WHO investigated the etiology of acute diarrhea that occurred from 1976-1979 in a global cohort of infants and young children. Rotaviruses were found to be major pathogens worldwide, whereas the Norwalk virus could not be detected using a radioimmunoassay. The aim of this study is to re-evaluate the role and diversity of rotaviruses and noroviruses in the original cohort using more sensitive current technologies. Stools collected from Asia, Africa, and South America (n = 485) were evaluated for viral genotypes by RT-PCR and sequencing. Rotaviruses were detected in 28.9% and noroviruses in 9.7% of the specimens, with G1 rotaviruses and GII noroviruses accounting for the majority of each respective virus. Various strains in this study predated the currently assigned dates of discovery for their particular genotype, and in addition, two noroviruses (KL45 and T091) could not be assigned to current genotypes. Phylogenetic analyses demonstrated a relative constancy in circulating rotavirus genotypes over time, with several genotypes from this study becoming established in the current repertoire of viral species. Similarly, GII noroviruses have maintained dominance, with GII.4 noroviruses continuing as a predominant genotype over time. Taken together, the complex molecular epidemiology of rotaviruses and noroviruses circulating in the 1970's is consistent with current patterns, an important consideration in the design of multivalent vaccines to control these viruses.
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Project description:Transmissible vaccines may provide a promising solution for improving the control of infectious disease, particularly zoonotic pathogens with wildlife reservoirs. Although it is well known that heterogeneity in pathogen transmission impacts the spread of infectious disease, the effects of heterogeneity on vaccine transmission are largely unknown. Here we develop and analyze a mathematical model that quantifies the potential benefits of a transmissible vaccine in a population where transmission is heterogeneous between two subgroups. Our results demonstrate that the effect of heterogeneity on the benefit of vaccine transmission largely depends on the vaccine design and the pattern of vaccine administration across subgroups. Specifically, our results show that in most cases a transmissible vaccine designed to mirror the transmission of the pathogen is optimal. If the vaccination effort can be preferentially biased towards a given subgroup, a vaccine with a pattern of transmission opposite to that of the pathogen can become optimal in some cases. To better understand the consequences of heterogeneity on the effectiveness of a transmissible vaccine in the real world, we parameterized our model using data from Sin Nombre virus in deer mice (Peromyscus maniculatus). The results of this analysis reveal that when a vaccination campaign is limited in vaccine availability, a traditional vaccine must be administered primarily to males for the spread of Sin Nombre virus to be prevented. In contrast, a transmissible vaccine remains effective even when it cannot be preferentially administered to males.
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Project description:BackgroundTo assess the prevalence and evolution of transmitted drug resistance (TDR) in Belgium, a total of 3708 baseline human immunodeficiency virus (HIV)-1 polymerase sequences from patients diagnosed between 2013 and 2019 were analyzed.MethodsProtease and reverse-transcriptase HIV-1 sequences were collected from the 7 national Aids Reference Laboratories. Subtype determination and drug resistance scoring were performed using the Stanford HIV Drug Resistance Database. Trends over time were assessed using linear regression, and the maximum likelihood approach was used for phylogenetic analysis.ResultsA total of 17.9% of the patients showed evidence of TDR resulting in at least low-level resistance to 1 drug (Stanford score ≥15). If only the high-level mutations (Stanford score ≥60) were considered, TDR prevalence dropped to 6.3%. The majority of observed resistance mutations impacted the sensitivity for nonnucleoside reverse-transcriptase inhibitors (NNRTIs) (11.4%), followed by nucleoside reverse-transcriptase inhibitors (6.2%) and protease inhibitors (2.4%). Multiclass resistance was observed in 2.4%. Clustered onward transmission was evidenced for 257 of 635 patients (40.5%), spread over 25 phylogenetic clusters.ConclusionsThe TDR prevalence remained stable between 2013 and 2019 and is comparable to the prevalence in other Western European countries. The high frequency of NNRTI mutations requires special attention and follow-up. Phylogenetic analysis provided evidence for local clustered onward transmission of some frequently detected mutations.
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Project description:The aim of this study was to evaluate the potential role of office fomites in respiratory (human parainfluenza virus 1-HPIV1, human parainfluenza virus 3-HPIV3) and enteric (norovirus GI-NoV GI, norovirus GII-NoV GII) viruses transmission by assessing the occurrence of these viruses on surfaces in office buildings. Between 2016 and 2017, a total of 130 surfaces from open-space and non-open-space rooms in office buildings located in one city were evaluated for HPIV1, HPIV3, NoV GI, and NoV GII viral RNA presence. Detection of viruses was performed by RT-qPCR method. Study revealed 27 positive samples, among them 59.3% were HPIV3-positive, 25.9% HPIV1-positive, and 14.8% NoV GII-positive. All tested surfaces were NoV GI-negative. Statistical analysis of obtained data showed that the surfaces of office equipment including computer keyboards and mice, telephones, and desktops were significantly more contaminated with respiratory viruses than the surfaces of building equipment elements such as door handles, light switches, or ventilation tracts (? 2 p = 0.006; Fisher's Exact p = 0.004). All examined surfaces were significantly more contaminated with HPIVs than NoVs (? 2 p = 0.002; Fisher's Exact p = 0.003). Office fomites in open-space rooms were more often contaminated with HPIVs than with NoVs (? 2 p = 0.016; Fisher's Exact p = 0.013). The highest average concentration of HPIVs RNA copies was observed on telephones (1.66 × 102 copies/100 cm2), while NoVs on the light switches (1.40 × 102 copies/100 cm2). However, the Kruskal-Wallis test did not show statistically significant differences in concentration levels of viral RNA copies on surfaces between the all tested samples. This study unequivocally showed that individuals in office environment may have contact with both respiratory and enteric viral particles present on frequently touched surfaces.
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Project description:West-Central Africa is an epicenter of the HIV pandemic; endemic to Cameroon are HIV-1 viruses belonging to all (sub)subtypes and numerous Circulating Recombinant Forms (CRFs). The rural villages of Cameroon harbor many strains of HIV-1, though these areas are not as well monitored as the urban centers. In the present study, 82 specimens obtained in 2000 and 2001 from subjects living in the rural villages of the South and West Regions of Cameroon were subtyped in gag, pol, and env and compared to 90 specimens obtained in 2006-2008 in the same regions, in order to analyze HIV-1 evolution in these rural areas. It was found that in the South Region, the proportion of unique recombinant forms (URFs) remained constant (~40%), while the amount of URFs containing fragments of a CRF increased by 25%. (Sub)subtypes A1, F2, H, and K, and CRF09_cpx, identified in 2000 and 2001, were replaced by CRFs 01_AE, 13_cpx, 14_BG, and 18_cpx in 2006-2008. In the West Region, (sub)subtypes A2, C, G, and H, and CRFs 01_AE and 09_cpx, identified in 2000-2001, were replaced by sub-subtype A1 and CRFs 25_cpx and 37_cpx in 2006-2008. The proportion of URFs in the West Region dropped significantly over the time period by 43%. In both Regions, the proportion of CRF02_AG increased at all loci. These findings demonstrate that the evolution of HIV-1 is distinct for each endemic region, and suggests that the proportion of URFs containing CRF fragments is increasing as the genetic identity of the virus continues to shift dramatically. This highlights the concern that subtype-specific vaccines may not be relevant in Cameroon, and that the distribution of viral diversity in these regions of Cameroon must be carefully monitored.
| S-EPMC2975583 | biostudies-literature
Project description:The nucleocapsid (N) protein of a coronavirus plays a crucial role in virus assembly and in its RNA transcription. It is important to characterize a virus at the nucleotide level to discover the virus's genomic sequence variations and similarities relative to other viruses that could have an impact on the functions of its genes and proteins. This entails a comprehensive and comparative analysis of the viral genomes of interest for preferred nucleotides, codon bias, nucleotide changes at the 3rd position (NT3s), synonymous codon usage and relative synonymous codon usage. In this study, the variations in the N proteins among 13 different coronaviruses (CoVs) were analysed at the nucleotide and amino acid levels in an attempt to reveal how these viruses adapt to their hosts relative to their preferred codon usage in the N genes. The results revealed that, overall, eighteen amino acids had different preferred codons and eight of these were over-biased. The N genes had a higher AT% over GC% and the values of their effective number of codons ranged from 40.43 to 53.85, indicating a slight codon bias. Neutrality plots and correlation analyses showed a very high level of GC3s/GC correlation in porcine epidemic diarrhea CoV (pedCoV), followed by Middle East respiratory syndrome-CoV (MERS CoV), porcine delta CoV (dCoV), bat CoV (bCoV) and feline CoV (fCoV) with r values 0.81, 0.68, -0.47, 0.98 and 0.58, respectively. These data implied a high rate of evolution of the CoV genomes and a strong influence of mutation on evolutionary selection in the CoV N genes. This type of genetic analysis would be useful for evaluating a virus's host adaptation, evolution and is thus of value to vaccine design strategies.
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Project description:The human respiratory syncytial virus (hRSV) is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. Such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently to respiratory failure. Upon infection, different pattern recognition receptors recognize the virus and trigger the innate immune response against the hRSV. Further, T cell immunity plays an important role for virus clearance. Based on animal studies, it is thought that the host immune response to hRSV is based on a biased T helper (Th)-2 and Th17 T cell responses with the recruitment of T cells, neutrophils and eosinophils to the lung, causing inflammation and tissue damage. In contrast, human immunity against RSV has been shown to be more complex with no definitive T cell polarization profile. Nowadays, only a humanized monoclonal antibody, known as palivizumab, is available to protect against hRSV infection in high-risk infants. However, such treatment involves several injections at a significantly high cost. For these reasons, intense research has been focused on finding novel vaccines or therapies to prevent hRSV infection in the population. Here, we comprehensively review the recent literature relative to the immunological features during hRSV infection, as well as the new insights into preventing the disease caused by this virus.
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Project description:BackgroundIn recent decades, the GII.4 norovirus genotype has predominated in epidemics worldwide and been associated with an increased rate of evolutionary change. In 2014, a novel GII.17 variant emerged and persisted, causing large outbreaks of gastroenteritis in China and sporadic infections globally. The origin, evolution, and transmission history of this new variant are largely unknown.MethodsWe generated 103 full capsid and 8 whole-genome sequences of GII.17 strains collected between August 2013 and November 2015 in Guangdong, China. Phylogenetic analyses were performed by integrating our data with those for all publically available GII.17 sequences.ResultsThe novel emergent lineage GII.17_Kawasaki_2014 most likely originated from Africa around 2001 and evolved at a rate of 5.6 × 10(-3) substitutions/site/year. Within this lineage, a new variant containing several important amino acid changes emerged around August 2013 and caused extensive epidemics in 2014-2015. The phylodynamic and epidemic history of the GII.17_Kawasaki lineage shows similarities with the pattern observed for GII.4 norovirus evolution. Virus movements from Hong Kong to neighboring coastal cities were frequently observed.ConclusionsOur results provide new insights into GII.17 norovirus evolution and transmission and highlight the potential for a rare norovirus genotype to rapidly replace existing strains and cause local epidemics.
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Project description:Dengue viruses (DENV) infect 50 to 100 million people each year. The spread of DENV-associated infections is one of the most serious public health problems worldwide, as there is no widely available vaccine or specific therapeutic for DENV infections. To address this, we developed a novel tetravalent dengue vaccine by utilizing virus-like particles (VLPs). We created recombinant DENV1 to -4 (DENV1-4) VLPs by coexpressing precursor membrane (prM) and envelope (E) proteins, with an F108A mutation in the fusion loop structure of E to increase the production of VLPs in mammalian cells. Immunization with DENV1-4 VLPs as individual, monovalent vaccines elicited strong neutralization activity against each DENV serotype in mice. For use as a tetravalent vaccine, DENV1-4 VLPs elicited high levels of neutralization activity against all four serotypes simultaneously. The neutralization antibody responses induced by the VLPs were significantly higher than those with DNA or recombinant E protein immunization. Moreover, antibody-dependent enhancement (ADE) was not observed against any serotype at a 1:10 serum dilution. We also demonstrated that the Zika virus (ZIKV) VLP production level was enhanced by introducing the same F108A mutation into the ZIKV envelope protein. Taken together, these results suggest that our strategy for DENV VLP production is applicable to other flavivirus VLP vaccine development, due to the similarity in viral structures, and they describe the promising development of an effective tetravalent vaccine against the prevalent flavivirus.IMPORTANCE Dengue virus poses one of the most serious public health problems worldwide, and the incidence of diseases caused by the virus has increased dramatically. Despite decades of effort, there is no effective treatment against dengue. A safe and potent vaccine against dengue is still needed. We developed a novel tetravalent dengue vaccine by using virus-like particles (VLPs), which are noninfectious because they lack the viral genome. Previous attempts of other groups to use dengue VLPs resulted in generally poor yields. We found that a critical amino acid mutation in the envelope protein enhances the production of VLPs. Our tetravalent vaccine elicited potent neutralizing antibody responses against all four DENV serotypes. Our findings can also be applied to vaccine development against other flaviviruses, such as Zika virus or West Nile virus.
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Project description:This study examined sleep research in athletes published between 1966 and 2019, through a bibliometric analysis of research output in the Scopus database. Following a robust assessment of titles, the bibliometric indicators of productivity for studies included in the final analysis were: Distribution of publications and citations (excluding self-citations), top ten active journals, countries, institutions and authors, single- and multi-country collaboration, and 25 top-cited papers. Out of the 1015 papers, 313 were included in the final analysis. The majority of the papers were research articles (n = 259; 82.8%) and published in English (n = 295; 94.3%). From 2011, there was a dramatic increase in papers published (n = 257; 82.1%) and citations (n = 3538; 91.0%). The number of collaborations increased after 2001, with papers published through international (n = 81; 25.9%) and national (n = 192; 61.3%) collaboration. Australia was the most prolific country in terms of number of publications (n = 97; 31.0%), and citations (n = 1529; 15.8%). In conclusion, after the beginning of the twenty-first century, the scientific production on sleep research in athletes has seen significant growth in publication and citation output. Future research should focus on interventions to improve sleep in athletes.
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