Abstract:
:The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs). Therefore, we hypothesized that these bystander cells could impact the interpretation of ADCC measurements. To investigate this, we evaluated the ability of antibodies to CD4i epitopes and broadly neutralizing Abs (bNAbs) to mediate ADCC measured by five ADCC assays commonly used in the field. Our results indicate that the uninfected bystander cells coated with gp120 are efficiently recognized by the CD4i ligands but not the bNabs. Consequently, the uninfected bystander cells substantially affect in vitro measurements made with ADCC assays that fail to identify responses against infected versus uninfected cells. Moreover, using an mRNA flow technique that detects productively infected cells, we found that the vast majority of HIV-1-infected cells in in vitro cultures or ex vivo samples from HIV-1-infected individuals are CD4 negative and therefore do not expose significant levels of CD4i epitopes. Altogether, our results indicate that ADCC assays unable to differentiate responses against infected versus uninfected cells overestimate responses mediated by CD4i ligands.IMPORTANCE Emerging evidence supports a role for antibody-dependent cellular cytotoxicity (ADCC) in protection against HIV-1 transmission and disease progression. However, there are conflicting reports regarding the ability of nonneutralizing antibodies targeting CD4-inducible (CD4i) Env epitopes to mediate ADCC. Here, we performed a side-by-side comparison of different methods currently being used in the field to measure ADCC responses to HIV-1. We found that assays which are unable to differentiate virus-infected from uninfected cells greatly overestimate ADCC responses mediated by antibodies to CD4i epitopes and underestimate responses mediated by broadly neutralizing antibodies (bNAbs). Our results strongly argue for the use of assays that measure ADCC against HIV-1-infected cells expressing physiologically relevant conformations of Env to evaluate correlates of protection in vaccine trials.
journal_name
mBiojournal_title
mBioauthors
Richard J,Prévost J,Baxter AE,von Bredow B,Ding S,Medjahed H,Delgado GG,Brassard N,Stürzel CM,Kirchhoff F,Hahn BH,Parsons MS,Kaufmann DE,Evans DT,Finzi Adoi
10.1128/mBio.00358-18subject
Has Abstractpub_date
2018-03-20 00:00:00issue
2issn
2150-7511pii
mBio.00358-18journal_volume
9pub_type
杂志文章相关文献
mBio文献大全abstract::Host cytokine responses to Brucella abortus infection are elicited predominantly by the deployment of a type IV secretion system (T4SS). However, the mechanism by which the T4SS elicits inflammation remains unknown. Here we show that translocation of the T4SS substrate VceC into host cells induces proinflammatory resp...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00418-12
更新日期:2013-02-19 00:00:00
abstract::Pathogens frequently employ eukaryotic linear motif (ELM)-rich intrinsically disordered proteins (IDPs) to perturb and hijack host cell networks for a productive infection. Mycobacterium tuberculosis has a relatively high percentage of IDPs in its proteome, the significance of which is not known. The Mycobacterium-spe...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01712-17
更新日期:2018-01-23 00:00:00
abstract::Mobile elements-plasmids and phages-are important components of microbial function and evolution via traits that they encode and their capacity to shuttle genetic material between species. We here report the unusually rich array of mobile elements within the genome of Arsenophonus nasoniae, the son-killer symbiont of ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02590-19
更新日期:2020-03-24 00:00:00
abstract:UNLABELLED:Diverse colony morphologies are a hallmark of Burkholderia pseudomallei recovered from infected patients. We observed that stresses that inhibit aerobic respiration shifted populations of B. pseudomallei from the canonical white colony morphotype toward two distinct, reversible, yet relatively stable yellow ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02462-14
更新日期:2015-02-03 00:00:00
abstract::Streptococcus gallolyticus subsp. gallolyticus is an emerging opportunistic pathogen responsible for septicemia and endocarditis in the elderly. Invasive infections by S. gallolyticus subsp. gallolyticus are strongly linked to the occurrence of colorectal cancer (CRC). It was previously shown that increased secondary ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.03189-20
更新日期:2021-01-05 00:00:00
abstract::Elegance is a prized quality in science that is associated with simplicity and explanatory power. This essay considers the qualities that make a scientific model, experiment, method, or theory "elegant," with a focus on the life sciences. We propose a definition of elegance that includes clarity, cleverness, correctne...
journal_title:mBio
pub_type: 社论
doi:10.1128/mBio.00043-18
更新日期:2018-02-20 00:00:00
abstract:UNLABELLED:The ability to cultivate food is an innovation that has produced some of the most successful ecological strategies on the planet. Although most well recognized in humans, where agriculture represents a defining feature of civilization, species of ants, beetles, and termites have also independently evolved sy...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02077-14
更新日期:2014-11-18 00:00:00
abstract:UNLABELLED:Elevated intracellular levels of the bacterial second messenger c-di-GMP are known to suppress motility and promote sessility. Bacterial chemotaxis guides motile cells in gradients of attractants and repellents over broad concentration ranges, thus allowing bacteria to quickly adapt to changes in their surro...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00001-13
更新日期:2013-03-19 00:00:00
abstract::Our current understanding of lipoprotein synthesis and localization in Gram-negative bacteria is based primarily on studies of Escherichia coli Newly synthesized E. coli prolipoproteins undergo posttranslational modifications catalyzed by three essential enzymes (Lgt, LspA, and Lnt). The mature lipoproteins are then s...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00911-20
更新日期:2020-05-19 00:00:00
abstract::The pharmacopeia used by physicians and laypeople in medieval Europe has largely been dismissed as placebo or superstition. While we now recognize that some of the materia medica used by medieval physicians could have had useful biological properties, research in this area is limited by the labor-intensive process of ...
journal_title:mBio
pub_type: 历史文章,杂志文章
doi:10.1128/mBio.03136-19
更新日期:2020-02-11 00:00:00
abstract::The acquisition and incorporation of genetic material between nonmating species, or horizontal gene transfer (HGT), has been frequently described for phylogenetically related organisms, but far less evidence exists for HGT between highly divergent organisms. Here we report the identification and characterization of a ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00005-11
更新日期:2011-02-15 00:00:00
abstract:UNLABELLED:Small RNAs play a critical role in host-pathogen interaction. Indeed, small RNA-mediated silencing or RNA interference (RNAi) is one of the earliest forms of antiviral immunity. Although it represents the main defense system against viruses in many organisms, the antiviral role of RNAi has not been clearly p...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00698-13
更新日期:2013-11-19 00:00:00
abstract::Glycoprotein B (gB), gD, and gH/gL constitute the fusion machinery of herpes simplex virus (HSV). Prior studies indicated that fusion occurs in a stepwise fashion whereby the gD/receptor complex activates the entire process, while gH/gL regulates the fusion reaction carried out by gB. Trimeric gB is a class III fusion...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00429-12
更新日期:2012-11-20 00:00:00
abstract::Our knowledge of cell cycle regulatory mechanisms in apicomplexan parasites is very limited. In this study, we describe a novel Toxoplasma gondii factor that has a vital role in chromosome replication and the regulation of cytoplasmic and nuclear mitotic structures, and we named this factor ECR1 for essential for chro...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00579-17
更新日期:2017-08-22 00:00:00
abstract::Bacteroides thetaiotaomicron is one of the most abundant gut symbiont species, whose contribution to host health through its ability to degrade dietary polysaccharides and mature the immune system is under intense scrutiny. In contrast, adhesion and biofilm formation, which are potentially involved in gut colonization...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00729-20
更新日期:2020-06-23 00:00:00
abstract::RNA-binding proteins (RBPs) play a major role during control of mRNA localization, stability, and translation and are central to most cellular processes. In the fission yeast Schizosaccharomyces pombe, the multiple K homology (KH) domain RBP Rnc1 downregulates the activity of the cell integrity pathway (CIP) via stabi...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02815-19
更新日期:2020-01-07 00:00:00
abstract::SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as the primary receptor to enter host cells and initiate the infection. The critical binding region of ACE2 is an ∼30-amino-acid (aa)-long helix. Here, we report the design of four stapled peptides based on the ACE2 helix, which is expected to bind to SARS-C...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02451-20
更新日期:2020-12-11 00:00:00
abstract::ABSTRACT The type VII secretion systems are conserved across mycobacterial species and in many Gram-positive bacteria. While the well-characterized Esx-1 pathway is required for the virulence of pathogenic mycobacteria and conjugation in the model organism Mycobacterium smegmatis, Esx-3 contributes to mycobactin-media...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01073-14
更新日期:2014-05-06 00:00:00
abstract::HLA-C-mediated antigen presentation induces the killing of human immunodeficiency virus (HIV)-infected CD4+ T cells by cytotoxic T lymphocytes (CTLs). To evade killing, many HIV-1 group M strains decrease HLA-C surface levels using their accessory protein Vpu. However, some HIV-1 group M isolates lack this activity, p...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00782-20
更新日期:2020-07-14 00:00:00
abstract::The alarmone (p)ppGpp plays pivotal roles in basic bacterial stress responses by increasing tolerance of various nutritional limitations and chemical insults, including antibiotics. Despite intensive studies since (p)ppGpp was discovered over 4 decades ago, (p)ppGpp binding proteins have not been systematically identi...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02188-17
更新日期:2018-03-06 00:00:00
abstract::Malaria parasites increase their host erythrocyte's permeability to various nutrients, fueling intracellular pathogen development and replication. The plasmodial surface anion channel (PSAC) mediates this uptake and is linked to the parasite-encoded RhopH complex, consisting of CLAG3, RhopH2, and RhopH3. While interac...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01354-20
更新日期:2020-09-08 00:00:00
abstract:UNLABELLED:Type III secretion systems (T3SS) translocate effector proteins into target cells in order to disrupt or modulate host cell signaling pathways and establish replicative niches. However, recognition of T3SS activity by cytosolic pattern recognition receptors (PRRs) of the nucleotide-binding domain leucine ric...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02095-14
更新日期:2015-02-17 00:00:00
abstract:UNLABELLED:The protein YfeX from Escherichia coli has been proposed to be essential for the process of iron removal from heme by carrying out a dechelation of heme without cleavage of the porphyrin macrocycle. Since this proposed reaction is unique and would represent the first instance of the biological dechelation of...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00248-11
更新日期:2011-11-08 00:00:00
abstract::Nonflagellar type III secretion systems (nf T3SSs) form a cell surface needle-like structure and an associated translocon that deliver bacterial effector proteins into eukaryotic host cells. This involves a tightly regulated hierarchy of protein secretion. A switch involving SctP and SctU stops secretion of the needle...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01149-18
更新日期:2018-10-02 00:00:00
abstract:UNLABELLED:Members of the clonally variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediate adhesion of infected erythrocytes (IEs) to vascular receptors. PfEMP1 expression is normally confined to nanoscale knob protrusions on the IE surface membrane. To investigate the relationship between ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01456-15
更新日期:2015-10-06 00:00:00
abstract::Proteins that metabolize or bind the nucleotide second messenger cyclic diguanylate regulate a wide variety of important processes in bacteria. These processes include motility, biofilm formation, cell division, differentiation, and virulence. The role of cyclic diguanylate signaling in the lifestyle of Legionella pne...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00316-10
更新日期:2011-01-11 00:00:00
abstract::Many Gram-negative bacterial pathogens require a type 3 secretion system (T3SS) to deliver effector proteins into eukaryotic cells. Contact of the tip complex of the T3SS with a target eukaryotic cell initiates secretion of the two bacterial proteins that assemble into the translocon pore in the plasma membrane. The t...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00877-19
更新日期:2019-05-28 00:00:00
abstract::The epidemiology of methicillin-resistant Staphylococcus aureus has changed considerably over the last 3 decades, including the recognition of lineages associated with the community and with livestock exposure, in addition to nosocomial strains. A recent study by R. N. Sieber, R. L. Skov, J. Nielsen, J. Schulz, et al....
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.02459-18
更新日期:2018-12-11 00:00:00
abstract::The diversity of the genetic code systems used by microbes on earth is yet to be elucidated. It is known that certain methanogenic archaea employ an alternative system for cysteine (Cys) biosynthesis and encoding; tRNACys is first acylated with phosphoserine (Sep) by O-phosphoseryl-tRNA synthetase (SepRS) and then con...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00561-17
更新日期:2017-05-09 00:00:00
abstract:UNLABELLED:Enoyl-acyl carrier protein (enoyl-ACP) reductase catalyzes the last step of the elongation cycle in the synthesis of bacterial fatty acids. The Enterococcus faecalis genome contains two genes annotated as enoyl-ACP reductases, a FabI-type enoyl-ACP reductase and a FabK-type enoyl-ACP reductase. We report tha...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00613-13
更新日期:2013-10-01 00:00:00