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Nature Communications May 2023The genomes of most protozoa encode families of variant surface antigens. In some parasitic microorganisms, it has been demonstrated that mutually exclusive changes in...
The genomes of most protozoa encode families of variant surface antigens. In some parasitic microorganisms, it has been demonstrated that mutually exclusive changes in the expression of these antigens allow parasites to evade the host's immune response. It is widely assumed that antigenic variation in protozoan parasites is accomplished by the spontaneous appearance within the population of cells expressing antigenic variants that escape antibody-mediated cytotoxicity. Here we show, both in vitro and in animal infections, that antibodies to Variant-specific Surface Proteins (VSPs) of the intestinal parasite Giardia lamblia are not cytotoxic, inducing instead VSP clustering into liquid-ordered phase membrane microdomains that trigger a massive release of microvesicles carrying the original VSP and switch in expression to different VSPs by a calcium-dependent mechanism. This novel mechanism of surface antigen clearance throughout its release into microvesicles coupled to the stochastic induction of new phenotypic variants not only changes current paradigms of antigenic switching but also provides a new framework for understanding the course of protozoan infections as a host/parasite adaptive process.
Topics: Animals; Giardia lamblia; Giardiasis; Parasites; Antigens, Surface; Antigens, Protozoan; Intestinal Diseases, Parasitic; Antibodies; Antigenic Variation; Protozoan Proteins
PubMed: 37137944
DOI: 10.1038/s41467-023-38317-8 -
Microbiology and Immunology Jan 2022The serological diagnosis of acute hepatitis B virus (HBV) infection after recent exposure has been established by the hepatitis B virus surface antigen (HBsAg) and... (Review)
Review
Detection of the serological markers hepatitis B virus surface antigen (HBsAg) and hepatitis B core IgM antibody (anti-HBcIgM) in the diagnosis of acute hepatitis B virus infection after recent exposure.
The serological diagnosis of acute hepatitis B virus (HBV) infection after recent exposure has been established by the hepatitis B virus surface antigen (HBsAg) and anti-hepatitis B core IgM antibody (anti-HBcIgM) detection in serum, sometimes accompanied by the detection of hepatitis B "e" antigen (HBeAg). Despite this characteristic serological profile, misdiagnosis can occur in cases of unexpected or atypical behavior of the serological markers in the bloodstream, or if the true meaning of its expression is not properly investigated, or even if there is a possibility of interference from factors not necessarily linked to the infectious process, in the detection of these markers. This review discusses the influence of these variables on laboratory results for these two serological markers and, therefore, the potential risk of these variables compromising the correct diagnosis of acute infection after recent HBV exposure.
Topics: Antigens, Surface; DNA, Viral; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B e Antigens; Hepatitis B virus; Humans; Immunoglobulin M
PubMed: 34528725
DOI: 10.1111/1348-0421.12943 -
Frontiers in Immunology 2022infection causes the most severe form of malaria. It has been hypothesized that directly suppresses host immune responses because sufficient acquired immunity is often... (Review)
Review
infection causes the most severe form of malaria. It has been hypothesized that directly suppresses host immune responses because sufficient acquired immunity is often not induced even by repeated infections in malaria-endemic areas. It is known that many kinds of -derived proteins are expressed on the surface of -infected erythrocytes (IEs), and these proteins have long been thought to be a key to the elucidation of the host immune evasion mechanisms. Our recent studies have revealed that the -derived erythrocyte surface antigen, RIFIN, the largest multiple gene family protein in the genome, suppresses host immune cell activation through direct interaction with human inhibitory immune receptors. In this review, we will discuss the molecular mechanisms for host immune evasion by -infected erythrocyte surface antigens. In addition, we will discuss the recently identified host immune response to using specialized antibodies that target host--derived molecule interactions.
Topics: Antigens, Protozoan; Antigens, Surface; Erythrocytes; Humans; Immune Evasion; Malaria; Malaria, Falciparum; Plasmodium falciparum; Protozoan Proteins
PubMed: 35784341
DOI: 10.3389/fimmu.2022.901864 -
PLoS Neglected Tropical Diseases Aug 2017TSSA (Trypomastigote Small Surface Antigen) is an antigenic, adhesion molecule displayed on the surface of Trypanosoma cruzi trypomastigotes. TSSA displays substantial...
BACKGROUND
TSSA (Trypomastigote Small Surface Antigen) is an antigenic, adhesion molecule displayed on the surface of Trypanosoma cruzi trypomastigotes. TSSA displays substantial sequence identity to members of the TcMUC gene family, which code for the trypomastigote mucins (tGPI-mucins). In addition, TSSA bears sequence polymorphisms among parasite strains; and two TSSA variants expressed as recombinant molecules (termed TSSA-CL and TSSA-Sy) were shown to exhibit contrasting features in their host cell binding and signaling properties.
METHODS/PRINCIPLE FINDINGS
Here we used a variety of approaches to get insights into TSSA structure/function. We show that at variance with tGPI-mucins, which rely on their extensive O-glycoslylation to achieve their protective function, TSSA seems to be displayed on the trypomastigote coat as a hypo-glycosylated molecule. This has a functional correlate, as further deletion mapping experiments and cell binding assays indicated that exposition of at least two peptidic motifs is critical for the engagement of the 'adhesive' TSSA variant (TSSA-CL) with host cell surface receptor(s) prior to trypomastigote internalization. These motifs are not conserved in the 'non-adhesive' TSSA-Sy variant. We next developed transgenic lines over-expressing either TSSA variant in different parasite backgrounds. In strict accordance to recombinant protein binding data, trypomastigotes over-expressing TSSA-CL displayed improved adhesion and infectivity towards non-macrophagic cell lines as compared to those over-expressing TSSA-Sy or parental lines. These phenotypes could be specifically counteracted by exogenous addition of peptides spanning the TSSA-CL adhesion motifs. In addition, and irrespective of the TSSA variant, over-expression of this molecule leads to an enhanced trypomastigote-to-amastigote conversion, indicating a possible role of TSSA also in parasite differentiation.
CONCLUSION/SIGNIFICANCE
In this study we provided novel evidence indicating that TSSA plays an important role not only on the infectivity and differentiation of T. cruzi trypomastigotes but also on the phenotypic variability displayed by parasite strains.
Topics: Amino Acid Sequence; Animals; Antigens, Protozoan; Antigens, Surface; Cell Differentiation; Chagas Disease; Chlorocebus aethiops; Gene Expression Regulation; Genes, Protozoan; HeLa Cells; Humans; Mucins; Recombinant Proteins; Trypanosoma cruzi; Vero Cells
PubMed: 28800609
DOI: 10.1371/journal.pntd.0005856 -
Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models.Virulence Dec 2021Hepatitis B virus (HBV) middle surface antigen (MHBs) mutation or deletion occurs in patients with chronic HBV infection. However, the functional role of MHBs in HBV...
Hepatitis B virus (HBV) middle surface antigen (MHBs) mutation or deletion occurs in patients with chronic HBV infection. However, the functional role of MHBs in HBV infection is still an enigma. Here, we reported that 7.33% (11/150) isolates of CHB patients had MHBs start codon mutations compared with 0.00% (0/146) in acute hepatitis B (AHB) patients. Interestingly, MHBs loss accounted for 11.88% (126/1061) isolates from NCBI GenBank, compared with 0.09% (1/1061) and 0.00% (0/1061) for HBV large surface antigen (LHBs) loss and HBV small surface antigen (SHBs) loss, respectively. One persistent HBV clone of genotype B (B56, MHBs loss) from a CHB patient was hydrodynamically injected into BALB/c mice. B56 persisted for >70 weeks in BALB/c mice, whereas B56 with restored MHBs (B56) was quickly cleared within 28 days. Serum cytokine assays demonstrated that CXCL1, CXCL2, IL-6 and IL-33 were significantly increased during rapid HBV clearance in B56 mice. Furthermore, the enhancers and promoters of B56 were proved to be required for B56 persistence in mice. Ablating MHBs expression improved the persistence of a new clone (HBV1.3, genotype B) which was recreated by using enhancers and promoters of B56. These data demonstrated that MHBs deletion can promote the persistence of specific HBV variants in a hydrodynamic mouse model. MHBs re-expression restored a rapid clearance of HBV, which was accompanied by cytokine responses including the elevation of CXCL1, CXCL2, IL-6 and IL-33.
Topics: Animals; Antigens, Surface; Disease Models, Animal; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Interleukin-33; Interleukin-6; Mice; Mice, Inbred BALB C
PubMed: 34738866
DOI: 10.1080/21505594.2021.1999130 -
Malaria Journal Mar 2017Although a number of Plasmodium vivax proteins have been identified, few have been investigated as potential vaccine candidates. This study characterized the Plasmodium...
BACKGROUND
Although a number of Plasmodium vivax proteins have been identified, few have been investigated as potential vaccine candidates. This study characterized the Plasmodium vivax merozoite surface antigen 180 (PvMSA180, PVX_094920), a novel P. vivax antigenic protein.
METHODS
The target gene was amplified as four overlapping domains (D1, D2, D3 and D4) to enable expression of the recombinant protein using cell-free and bacterial expression systems. The recombinant PvMSA180 proteins were used in protein microarrays to evaluate the humoral immune response of 72 vivax-infected patients and 24 vivax-naïve individuals. Antibodies produced in mice against the PvMSA180-D1 and -D4 domains were used to assess the subcellular localization of schizont-stage parasites with immunofluorescence assays. A total of 51 pvmsa180 sequences from 12 countries (41 sequences from PlasmoDB and 6 generated in this study) were used to determine the genetic diversity and genealogical relationships with DNAsp and NETWORK software packages, respectively.
RESULTS
PvMSA180 consists of 1603 amino acids with a predicted molecular mass of 182 kDa, and has a signal peptide at the amino-terminus. A total of 70.8% of patients (51/72) showed a specific antibody response to at least one of the PvMSA180 domains, and 20.8% (15/72) exhibited a robust antibody response to at least three of the domains. These findings suggest that PvMSA180 is targeted by the humoral immune response during natural infection with P. vivax. Immunofluorescence analysis demonstrated that PvMSA180 is localized on the merozoite surface of schizont-stage parasites, and pvmsa180 sequences originating from various geographic regions worldwide showed low genetic diversity. Twenty-two haplotypes were found, and haplotype 6 (Hap_6, 77%) of pvmsa180 was detected in isolates from six countries.
CONCLUSIONS
A novel P. vivax surface protein, PvMSA180, was characterized in this study. Most of P. vivax-infected patients had specific antibodies against particular antigenic domains, indicating that this protein is immunogenic in naturally exposed populations. Genetic analysis of worldwide isolates showed that pvmsa180 is less polymorphic than other well-known candidates and that some haplotypes are common to several countries. However, additional studies with a larger sample size are necessary to evaluate the antibody responses in geographically separated populations, and to identify the function of PvMSA180 during parasite invasion.
Topics: Adolescent; Adult; Animals; Antibodies, Protozoan; Antigens, Protozoan; Antigens, Surface; Female; Genetic Variation; Humans; Male; Merozoites; Mice, Inbred BALB C; Microscopy, Fluorescence; Molecular Weight; Phylogeography; Plasmodium vivax; Protein Sorting Signals; Young Adult
PubMed: 28351409
DOI: 10.1186/s12936-017-1760-9 -
The Journal of Biological Chemistry Apr 2010Toxoplasma gondii, the etiological agent of toxoplasmosis, utilizes stage-specific expression of antigenically distinct glycosylphosphatidylinositol-tethered surface...
Toxoplasma gondii, the etiological agent of toxoplasmosis, utilizes stage-specific expression of antigenically distinct glycosylphosphatidylinositol-tethered surface coat proteins to promote and establish chronic infection. Of the three infective stages of T. gondii, sporozoites are encapsulated in highly infectious oocysts that have been linked to large scale outbreaks of toxoplasmosis. SporoSAG (surface antigen glycoprotein) is the dominant surface coat protein expressed on the surface of sporozoites. Using a bioinformatic approach, we show that SporoSAG clusters with the SAG2 subfamily of the SAG1-related superfamily (SRS) and is non-polymorphic among the 11 haplogroups of T. gondii strains. In contrast to the immunodominant SAG1 protein expressed on tachyzoites, SporoSAG is non-immunogenic during natural infection. We report the 1.60 A resolution crystal structure of SporoSAG solved using cadmium single anomalous dispersion. SporoSAG crystallized as a monomer and displays unique features of the SRS beta-sandwich fold relative to SAG1 and BSR4. Intriguingly, the structural diversity is localized to the upper sheets of the beta-sandwich fold and may have important implications for multimerization and host cell ligand recognition. The structure of SporoSAG also reveals an unexpectedly acidic surface that contrasts with the previously determined SAG1 and BSR4 structures where a basic surface is predicted to play a role in binding negatively charged glycosaminoglycans. Our structural and functional characterization of SporoSAG provides a rationale for the evolutionary divergence of this key SRS family member.
Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Antigens, Surface; Base Sequence; Crystallography, X-Ray; DNA, Protozoan; Genes, Protozoan; Humans; Models, Molecular; Phylogeny; Protein Structure, Secondary; Protozoan Proteins; Recombinant Proteins; Static Electricity; Toxoplasma; Toxoplasmosis
PubMed: 20164173
DOI: 10.1074/jbc.M109.054866 -
Frontiers in Immunology 2021, a major infectious agent of water buffalo hemolytic babesiosis, is transmitted by . However, no effective vaccine is available. Essential antigens that are involved in...
, a major infectious agent of water buffalo hemolytic babesiosis, is transmitted by . However, no effective vaccine is available. Essential antigens that are involved in parasite invasion of host red blood cells (RBCs) are potential vaccine candidates. Therefore, the identification and the conduction of functional studies of essential antigens are highly desirable. Here, we evaluated the function of merozoite surface antigen 2c1 (BoMSA-2c1), which belongs to the variable merozoite surface antigen (VMSA) family in . We developed a polyclonal antiserum against the purified recombinant (r)BoMSA-2c1 protein. Immunofluorescence staining results showed that BoMSA-2c1 was expressed only on extracellular merozoites, whereas the antigen was undetectable in intracellular parasites. RBC binding assays suggested that BoMSA-2c1 specifically bound to buffalo erythrocytes. Cytoadherence assays using a eukaryotic expression system further verified the binding and inhibitory ability of BoMSA-2c1. We found that BoMSA-2c1 with a GPI domain was expressed on the surface of HEK293T cells that bound to water buffalo RBCs, and that the anti-rBoMSA2c1 antibody inhibited this binding. These results indicated that BoMSA-2c1 was involved in mediating initial binding to host erythrocytes of Identification of the occurrence of binding early in the invasion process may facilitate understanding of the growth characteristics, and may help in formulating strategies for the prevention and control of this parasite.
Topics: Animals; Antigens, Protozoan; Antigens, Surface; Babesia; Babesiosis; Buffaloes; Cell Adhesion; Erythrocytes; HEK293 Cells; Humans; Merozoites; Protozoan Proteins
PubMed: 34079537
DOI: 10.3389/fimmu.2021.623492 -
PloS One 2022Myelodysplastic syndrome (MDS) is a heterogeneous hematopoietic stem cell disorder with thrombocytopenia. Flow cytometric immunophenotyping of blood cells has been...
OBJECTIVES
Myelodysplastic syndrome (MDS) is a heterogeneous hematopoietic stem cell disorder with thrombocytopenia. Flow cytometric immunophenotyping of blood cells has been instrumental in diagnosis as co-criteria, but the data regarding platelets remains lacking. This study aims to determine if there is a difference in surface antigen levels on platelets by comparing surface antigen levels in MDS patients and healthy control subjects. Concurrently, as flow cytometric gating can reveal the diameter of cells, this study will investigate differences in giant platelet percentage by comparing these percentages in high- and low-risk MDS patients.
STUDY DESIGN
Twenty newly diagnosed MDS patients were enrolled in this study. Platelet surface antigen levels were determined by measuring the binding capacity of antibodies with flow cytometry.
RESULTS
Platelets of MDS patients were shown to have a lower level of CD61 and higher levels of CD31 and CD36 than healthy controls. Judged by forward scatter (FSC), MDS patients' platelets appeared to be larger than those of healthy control subjects, whereas the MFI adjusted by diameter (MFI/FSC ratio) of CD31, CD41a, CD42a, CD42b and CD61 on platelets were lower in MDS patients than in healthy control subjects. There was a significant quantity of giant platelets found in MDS patients, and the high-risk MDS patients tended to have a higher percentage of giant platelets than low-risk patients. Conclusions: All the results indicate that MDS patients exhibit a lower antigen presentation (MFI) adjusted by diameter on platelets than healthy controls and the giant platelets detected by flow cytometry might correlate with the condition of MDS.
Topics: Humans; Immunophenotyping; Blood Platelets; Pilot Projects; Myelodysplastic Syndromes; Antigens, Human Platelet; Antigens, Surface
PubMed: 36409726
DOI: 10.1371/journal.pone.0278040 -
African Health Sciences Mar 2022Hepatitis B virus infection is one of the leading causes of liver diseases which occurs worldwide particularly in developing countries. It is often caused by prenatal...
Sero-prevalence of Hepatitis B virus surface antigen and associated factors among women of reproductive age in Bench Maji Zone, Southwest Ethiopia: Community based cross-sectional study.
BACKGROUND
Hepatitis B virus infection is one of the leading causes of liver diseases which occurs worldwide particularly in developing countries. It is often caused by prenatal transmission from mother to child or household transmission from a close contact during early childhood. It causes different complications like; jaundice, induces premature labor, and prematurity.
OBJECTIVE
The aim of this study was to estimate the sero-prevalence of hepatitis B virus surface antigen and associated factors among women of reproductive age in Bench Maji Zone, South West Ethiopia.
METHODS
A community-based cross-sectional study was conducted from December 15th, 2016 to February 15th, 2017. Multistage sampling technique was applied to select study participants. Logistic regression analysis was applied and p-values < 0.05 was used to see the significant association between dependent and independent variables.
RESULTS
A total of 330 participants were included in this study yielding 98.8% response rate. The sero-prevalence of hbsag among women of reproductive age was 28(8.5%). Having multiple sexual partners (AOR = 18.73, 95% CI = [3.65, 96.21) history of unprotected sex (AOR = 9.39, 95% CI = [1.64, 53.77) were found to be significantly associated with sero-prevalence of HBV.
CONCLUSIONS
The sero-prevalence of HBV infection among women of reproductive age was highly endemic. Hence, behavioral education and communication programs focusing on reduction of risky sexual behaviors should be designed to reduce HBV infection.
Topics: Antigens, Surface; Cross-Sectional Studies; Ethiopia; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Prevalence; Risk Factors; Surveys and Questionnaires
PubMed: 36032468
DOI: 10.4314/ahs.v22i1.58