Abstract:
:The four dengue virus serotypes (DENV1 to 4) cause dengue, a major public health problem worldwide. Individuals exposed to primary DENV infections develop serotype-specific neutralizing antibodies, including strongly neutralizing antibodies targeting quaternary epitopes. To date, no studies have measured the levels and kinetics of serum antibodies directed to such epitopes among populations in regions where dengue is endemic. Here, we use a recombinant DENV4 (rDENV4/3-M14) displaying a major DENV3 type-specific quaternary epitope recognized by human monoclonal antibody 5J7 to measure the proportion, magnitude, and kinetics of DENV3 type-specific neutralizing antibody responses targeting this epitope. Primary DENV3 sera from 30 individuals in a dengue hospital-based study in Nicaragua were studied 3, 6, 12, and 18 months post-infection, alongside samples collected annually 1 to 4 years post-primary DENV3 infection from 10 individuals in a cohort study in Nicaragua. We found substantial individual variation in the proportion of DENV3 type-specific neutralizing antibody titers attributed to the 5J7 epitope (range, 0 to 100%), with the mean significantly increasing from 22.6% to 41.4% from 3 to 18 months. We extended the transplanted DENV3 5J7 epitope on the virion (rDENV4/3-M16), resulting in increased recognition in several individuals, helping define the footprint of the epitope. However, 37% and 13% of the subjects still showed little to no recognition of the 5J7 epitope at 3 and 18 months, respectively, indicating that one or more additional DENV3 type-specific epitopes exist. Overall, this study demonstrates how DENV-immune plasma from populations from areas of endemicity, when coupled with structurally guided recombinant viruses, can help characterize the epitope-specific neutralizing antibody response in natural DENV infections, with direct implications for design and evaluation of dengue vaccines.IMPORTANCE The four serotypes of dengue virus cause dengue, a major public health burden worldwide, yet it has been challenging to develop a vaccine that is safe and equally effective against all four serotypes. More in-depth characterization of natural human neutralizing antibody responses is needed to identify determinants of protective antibody responses to all DENV serotypes. Here, we use hospital and cohort studies in a region where dengue is endemic to assess the proportion and kinetics of the DENV3 neutralizing antibody response directed to a quaternary epitope on DENV3 recognized by strongly neutralizing human monoclonal antibody 5J7, which was transplanted into a DENV4 backbone. We show that many individuals recognized the 5J7 epitope, but to various degrees over time, suggesting that additional DENV3-specific epitopes likely exist. Thus, characterization of epitope-specific neutralizing antibody responses in natural DENV infections can help define the footprint and repertoire of antibodies directed to DENV3 type-specific epitopes, with implications for dengue vaccine development.
journal_name
mBiojournal_title
mBioauthors
Andrade DV,Katzelnick LC,Widman DG,Balmaseda A,de Silva AM,Baric RS,Harris Edoi
10.1128/mBio.01205-17subject
Has Abstractpub_date
2017-09-19 00:00:00issue
5issn
2150-7511pii
mBio.01205-17journal_volume
8pub_type
杂志文章相关文献
mBio文献大全abstract::The opportunistic pathogen Pseudomonas aeruginosa is a leading cause of airway infection in cystic fibrosis (CF) patients. P. aeruginosa employs several hierarchically arranged and interconnected quorum sensing (QS) regulatory circuits to produce a battery of virulence factors such as elastase, phenazines, and rhamnol...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00532-20
更新日期:2020-04-07 00:00:00
abstract:UNLABELLED:The human fungal pathogen Cryptococcus neoformans is capable of infecting a broad range of hosts, from invertebrates like amoebas and nematodes to standard vertebrate models such as mice and rabbits. Here we have taken advantage of a zebrafish model to investigate host-pathogen interactions of Cryptococcus w...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01425-15
更新日期:2015-09-29 00:00:00
abstract:UNLABELLED:Clostridium perfringens enterotoxin (CPE) contributes to several important human gastrointestinal (GI) diseases. This toxin and its derivatives are also being explored for translational applications, i.e., cancer therapy or drug delivery. Some, but not all, members of the 24-member claudin (Cldn) family of m...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00594-12
更新日期:2013-01-15 00:00:00
abstract::Typhoid fever, caused by Salmonella enterica serovar Typhi, is a global public health concern due to increasing antimicrobial resistance (AMR). Characterization of S Typhi genomes for AMR and the evolution of different lineages, especially in countries where typhoid fever is endemic such as Bangladesh, will help publi...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02112-18
更新日期:2018-11-13 00:00:00
abstract::Arthritogenic alphaviruses such as Ross River and Chikungunya viruses cause debilitating muscle and joint pain and pose significant challenges in the light of recent outbreaks. How host immune responses are orchestrated after alphaviral infections and lead to musculoskeletal inflammation remains poorly understood. Her...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.03353-19
更新日期:2020-03-03 00:00:00
abstract:UNLABELLED:Small colony variants (SCVs) are naturally occurring subpopulations of bacteria. The clinical characteristics and treatment outcomes of patients with prosthetic joint infection (PJI) caused by staphylococcal SCVs are unknown. This study was a retrospective series of 113 patients with staphylococcal PJI, with...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01910-14
更新日期:2014-09-30 00:00:00
abstract::The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in sup...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00809-18
更新日期:2018-05-22 00:00:00
abstract::Throughout history, the yeast Saccharomyces cerevisiae has played a central role in human society due to its use in food production and more recently as a major industrial and model microorganism, because of the many genetic and genomic tools available to probe its biology. However, S. cerevisiae has proven difficult ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01410-18
更新日期:2018-09-25 00:00:00
abstract::Cystic fibrosis (CF) is caused by mutations in the CFTR gene and is associated with progressive and ultimately fatal infectious lung disease. There can be considerable variability in disease severity among individuals with the same CFTR mutations, and recent genome-wide association studies have identified secondary ge...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02073-17
更新日期:2017-12-19 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) Tat binds the viral RNA structure transactivation-responsive element (TAR) and recruits transcriptional cofactors, amplifying viral mRNA expression. The Tat inhibitor didehydro-cortistatin A (dCA) promotes a state of persistent latency, refractory to viral reactivation. Here...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01750-18
更新日期:2019-07-02 00:00:00
abstract::Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhib...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00668-19
更新日期:2019-04-23 00:00:00
abstract::Binding of Staphylococcus aureus to the large plasma glycoprotein von Willebrand factor (vWF) is controlled by hydrodynamic flow conditions. Currently, we know little about the molecular details of this shear-stress-dependent interaction. Using single-molecule atomic force microscopy, we demonstrate that vWF binds to ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00555-19
更新日期:2019-04-30 00:00:00
abstract::Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, remains a major cause of mortality and morbidity worldwide. One-third of the world population is infected with M. tuberculosis, and about 15 million people with latent tuberculosis infection (LTBI) reside in the United States. An estimated 10% of indiv...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02771-18
更新日期:2019-04-16 00:00:00
abstract::E165R, a highly specific dUTP nucleotidohydrolase (dUTPase) encoded by the African swine fever virus (ASFV) genome, is required for productive replication of ASFV in swine macrophages. Here, we solved the high-resolution crystal structures of E165R in its apo state and in complex with its product dUMP. Structural anal...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02483-19
更新日期:2019-10-29 00:00:00
abstract::Protein lysine acetylation, a prevalent posttranslational modification, regulates numerous crucial biological processes in cells. Nevertheless, how lysine acetylation interacts with other types of regulation to coordinate metabolism remains largely unknown owing to the complexity of the process. Here, using a represen...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00650-20
更新日期:2020-08-18 00:00:00
abstract::Infection of host cells by the respiratory syncytial virus (RSV) is characterized by the formation of spherical cytoplasmic inclusion bodies (IBs). These structures, which concentrate all the proteins of the polymerase complex as well as some cellular proteins, were initially considered aggresomes formed by viral dead...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01202-20
更新日期:2020-09-22 00:00:00
abstract::Epstein-Barr virus (EBV) infects and activates resting human B lymphocytes, reprograms them, induces their proliferation, and establishes a latent infection in them. In established EBV-infected cell lines, many viral latent genes are expressed. Their roles in supporting the continuous proliferation of EBV-infected B c...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01723-19
更新日期:2019-09-17 00:00:00
abstract::Diet influences health in multiple ways. One important effect of diet is on the gut microbiota. The effects of diet are often related to an individual's specific microbiota composition. The close links between health, diet, and gut microbiota are illustrated in a new mouse model of sepsis where the combination of a hi...
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.02335-19
更新日期:2019-10-08 00:00:00
abstract::The resurgence of pertussis (whooping cough) in countries with high vaccination coverage is alarming and invites reconsideration of the use of current acellular pertussis (aP) vaccines, which have largely replaced the old, reactogenic, whole-cell pertussis (wP) vaccine. Some drawbacks of these vaccines in terms of lim...
journal_title:mBio
pub_type: 社论
doi:10.1128/mBio.01339-14
更新日期:2014-06-10 00:00:00
abstract::The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studi...
journal_title:mBio
pub_type: 杂志文章,多中心研究
doi:10.1128/mBio.00266-12
更新日期:2012-09-18 00:00:00
abstract::The PCNA (proliferating cell nuclear antigen) ring plays central roles during DNA replication and repair. The yeast Elg1 RFC-like complex (RLC) is the principal unloader of chromatin-bound PCNA and thus plays a central role in maintaining genome stability. Here we identify a role for Elg1 in the unloading of PCNA duri...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01159-19
更新日期:2019-06-11 00:00:00
abstract::The human fungal pathogen Candida albicans causes lethal systemic infections because of its ability to grow and disseminate in a host. The C. albicans plasma membrane is essential for virulence by acting as a protective barrier and through its key roles in interfacing with the environment, secretion of virulence facto...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00254-11
更新日期:2011-12-27 00:00:00
abstract::The concept that anaerobic microorganisms can directly accept electrons from Fe(0) has been controversial because direct metal-microbe electron transfer has previously only been indirectly inferred. Fe(0) oxidation was studied with Geobacter sulfurreducens strain ACL, an autotrophic strain that was previously shown to...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00303-19
更新日期:2019-05-14 00:00:00
abstract::Mycobacterium bovis BCG is the only available vaccine for protection against tuberculosis (TB). While BCG protects children from severe disease, it has little impact on pulmonary disease in adults. A recombinant BCG vaccine BCG ΔureC::hly (strain VPM1002) is in advanced clinical trials and shows promise for improved v...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01370-16
更新日期:2016-08-30 00:00:00
abstract::Aspergillus fumigatus is the leading cause of pulmonary fungal diseases. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, in the last 10 years there have been several reports of azole resistance in A. fumigatus and new strategies are needed to com...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00816-20
更新日期:2020-06-16 00:00:00
abstract:UNLABELLED:Marine methane seeps are globally distributed geologic features in which reduced fluids, including methane, are advected upward from the subsurface. As a result of alkalinity generation during sulfate-coupled methane oxidation, authigenic carbonates form slabs, nodules, and extensive pavements. These carbona...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01348-15
更新日期:2015-12-22 00:00:00
abstract::Bacillus anthracis-a Gram-positive, spore-forming bacterium-causes anthrax, a highly lethal disease with high bacteremia titers. Such rapid growth requires ample access to nutrients, including iron. However, access to this critical metal is heavily restricted in mammals, which requires B. anthracis to employ petrobact...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01238-17
更新日期:2017-09-12 00:00:00
abstract::Chlamydiales species are obligate intracellular bacteria lacking a classical peptidoglycan sacculus but relying on peptidoglycan synthesis for cytokinesis. While septal peptidoglycan biosynthesis seems to be regulated by MreB actin and its membrane anchor RodZ rather than FtsZ tubulin in Chlamydiales, the mechanism of...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01128-19
更新日期:2019-07-16 00:00:00
abstract::Protein ubiquitylation regulates not only endocellular trafficking and proteasomal degradation but also the catalytic activity of enzymes. In Saccharomyces cerevisiae, we analyzed the composition of the ubiquitylated proteomes in strains lacking acetyltransferase Gcn5p, Ub-protease Ubp8p, or both to understand their i...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01504-20
更新日期:2020-08-11 00:00:00
abstract::Nineteen Thermococcus kodakarensis strains have been constructed, each of which synthesizes a different His(6)-tagged protein known or predicted to be a component of the archaeal DNA replication machinery. Using the His(6)-tagged proteins, stable complexes assembled in vivo have been isolated directly from clarified c...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00221-10
更新日期:2010-10-26 00:00:00