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Glycoproteins on the surface of immune cells play extremely important roles in response to pathogens. Yet, a systematic and time-resolved investigation of surface glycoproteins during the immune response remains to be explored. Integrating selective enrichment of surface glycoproteins with multiplexed proteomics, we globally and site-specifically quantified the dynamics of surface glycoproteins on THP-1 monocytes and macrophages in response to bacterial infection and during the monocyte-to-macrophage differentiation. The time-resolved analysis reveals transient changes and differential remodeling of surface glycoproteins on both cell types, and potential upstream regulators and downstream effects of the regulated glycoproteins. Besides, we identified novel surface glycoproteins participating in the immune response such as APMAP, and site-specific changes of glycoproteins. This study provides unprecedented information to deepen our understanding of glycoproteins and cellular activities.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface glycoproteins deposited to the NCBI GenBank from Europe, by the mid of April 2021 (12.04.2021) were analysed. At least one amino acid mutation relative to YP_009724390.1 referent SARS-CoV-2 surface glycoprotein: Wuhan-Hu-1 complete genome (NCBI accession: NC_045512) was found in 788 SARS-CoV-2 surface glycoproteins. Data was computed by NCBI Cobalt multiple alignment tool [1] (one country by another) and structured by special purpose application developed in Visual Studio 2019. Advanced data structures were used to organize computed data. Linked dataset lists program output: SARS-CoV-2 surface glycoprotein mutations per processed protein.

An effective vaccine for Hepatitis C Virus infection is still required despite existing direct- acting antiviral drugs available for treatment. In this study, the effective binding affinity of residues in three broadly neutralizing epitopes in E2 glycoprotein was detected by an innovative filtration strategy. In the first step, five, nine and eleven positions in EPI, EPII and EPIII were detected great variable, respectively. Furthermore, residues that could be substituted in these situations with high stability were indicated. In the second step, the mutants with the strongest affinity to neutralizing antibodies were predicted. I414M, T416S, I422V, I414M-T416S, and Q412N-I414M-T416S substitutions theoretically were exhibited as mutants with the best affinity binding. In conclusion, in current study the residues of E2 epitopes which have the best binding affinity to neutralizing antibodies were exhibited. Moreover, a distinct peptide library platform by a novel filtration strategy of epitopes was designed.

The blood collection and processing services in England are usually separate from the services in the hospitals where blood is matched for transfusion to specific patients. Non-haemolytic febrile transfusion reactions are common with standard platelet concentrates. The blood collection and processing services in England are usually separate from the services in the hospitals where blood is matched for transfusion to specific patients. The ingress of viable incompatible immune-competent cells during transfusion will usually be dealt with by the patient’s immune system. Platelet antigens, deriving from genetic polymorphisms among surface glycoproteins, can give rise to antibodies, complicating transfusion. Tests for anti-immunoglobulin A (IgA) should be included for all such cases with the first transfusion, even of red cells in optimal additive, since enough IgA is present in the residual plasma to cause reactions. Serological tests for syphilis are mandatory in most transfusion services, but their value is somewhat limited.

A unique feature of the African trypanosome Trypanosoma brucei is the presence of an outer layer made of densely packed variable surface glycoproteins (VSGs), which enables the cells to survive in the bloodstream. Although the VSG coat is critical to pathogenesis, how exactly the glycoproteins are organized at the nanoscale is poorly understood. Here, we show that multiparametric atomic force microscopy is a powerful nanoimaging tool for the structural and mechanical characterization of trypanosomes, in a label-free manner and in buffer solution. Directly correlated images of the structure and elasticity of trypanosomes enable us to identify multiple nanoscale mechanical heterogeneities on the cell surface. On a ∼250 nm scale, regions of softer (Young's modulus ∼50 kPa) and stiffer (∼100 kPa) elasticity alternate, revealing variations of the VSG coat and underlying structures. Our nanoimaging experiments show that the T. brucei cell surface is more heterogeneous than previously anticipated and offer promising prospects for the design of trypanocidal drugs targeting cell surface components., SCOPUS: ar.j, info:eu-repo/semantics/published

Background The World Health Organization targeted Trypanosoma brucei gambiense human African trypanosomiasis (gHAT) for elimination as a public health problem and for elimination of transmission. To measure gHAT elimination success with prevalences close to zero, highly specific diagnostics are necessary. Such a test exists in the form of an antibody-mediated complement lysis test, the trypanolysis test, but biosafety issues and technological requirements prevent its large-scale use. We developed an inhibition ELISA with high specificity and sensitivity that is applicable in regional laboratories in gHAT endemic countries. Methods The T. b. gambiense inhibition ELISA (g-iELISA) is based on the principle that binding of monoclonal antibodies to specific epitopes of T. b. gambiense surface glycoproteins can be inhibited by circulating antibodies of gHAT patients directed against the same epitopes. Using trypanolysis as reference test, the diagnostic accuracy of the g-iELISA was evaluated on plasma samples from 739 gHAT patients and 619 endemic controls and on dried blood spots prepared with plasma of 95 gHAT and 37 endemic controls. Results Overall sensitivity and specificity on plasma were, respectively, 98.0% (95% CI 96.7–98.9) and 99.5% (95% CI 98.6–99.9). With dried blood spots, sensitivity was 92.6% (95% CI 85.4–97.0), and specificity was 100% (95% CI 90.5–100.0). The g-iELISA is stable for at least 8 months when stored at 2–8°C. Conclusion The g-iELISA might largely replace trypanolysis for monitoring gHAT elimination and for postelimination surveillance. The g-iELISA kit is available for evaluation in reference laboratories in endemic countries., The novel Trypanosoma brucei gambiense inhibition ELISA (g-iELISA) is a high-throughput diagnostic applicable in regional laboratories for monitoring gambiense-HAT elimination. On plasma samples, sensitivity was 98.0% and specificity 99.5%, while on dried blood spots sensitivity was 92.6% and specificity 100%.

Cancer immunotherapy with T-cells that carry chimeric antigen receptors is currently on cutting edge of modern oncology. Autotransplantation of T-lymphocytes with chimeric receptor specific for certain tumor antigen proves to be clinically effective, but costly. Linear carriers of chimeric antigen receptors based on natural killer NK-92 cell culture may be an affordable alternative, however, this culture is resistant to lentiviral transduction. Recently, lentiviral vectors, pseudotyped with surface glycoproteins of the measles virus vaccine strain, have recently been successfully applied for transduction of primary immune cells. The aim of the work was to assess the efficiency of transduction of NK-92 cells with lentivirus vectors, pseudotyped with measles F and H surface glycoproteins, as well as to establish optimal conditions for selection of NK-92 transduced with the chimeric receptor against CD20 and to evaluate the culture’s cytotoxic potential. The results showed that the maximum infectious titer is achieved using the H∆18 variant in combination with F∆30, and the use of the TBK1/IKKɛ inhibitor BX795 results in additional 3-fold increase in the infectious titer. CAR-expressing NK-92 were able to suppress the proliferation of CD20+ cell line Raji in lower effector-to-target ratios than unmodified NK-92.

The discovery and development of novel antiviral drugs from natural sources is continuously increasing due to limitations of currently available drugs such as toxic side effects, drug residue risk factors, high costs, and poor therapeutic strategies. Also, there are very few known antiviral drugs that are effective against only specific viruses. Hence, the present study is intended to isolate and characterize potent antiviral compounds from the methanolic root extract ofSophora interruptaBedd. against avian paramyxovirus, Newcastle disease virus (NDV) and to distinguish the molecular basis of antiviral compounds. The two isolated flavonoids, maackiain (SR-1) and echinoisoflavanone (SR-2) exhibited the best antiviral activities against NDV infection in chicken embryo fibroblast cell lines compared to the standard antiviral drug, Ribavirin. Further, thein vitrostudies and quantitative PCR analysis suggests that these flavonoids inhibit the viral entry, replication, and transcription, which may be beneficial as a promising strategy for the treatment of viral infections. Besides, the molecular docking studies ofSR-1andSR-2exhibited high binding affinities of −7.6 and −8.0 kcal mol−1, respectively, and marked interactions with the NDV surface glycoprotein, hemagglutinin neuraminidase (HN). Also, thein silicotoxicity properties as well pharmacokinetic studies of isolates revealed them as pharmacologically potent antiviral compounds. © The Royal Society of Chemistry 2020. Council of Scientific and Industrial Research, India, CSIR The author WR thanks the Council of Scientic and Industrial Research (CSIR), New Delhi and the authors CB, AR, and PR are grateful to UGC-BSR, New Delhi for nancial assistance under CSIR-MRP and UGC-RFSMS (BSR) programs. Furthermore, all the authors are thankful to National Institute of Animal Biotechnology (NIAB), Hyderabad for providing laboratory facilities to carry out the viral studies.

Many viruses utilize cell-surface glycans as receptors for host cell entry. Viral surface glycoproteins specifically interact with glycan motifs, which strongly contributes to viral tropism. Recently, the interactions between host cell glycan receptors and the mumps virus (MuV) hemagglutinin-neuraminidase (MuV-HN) protein were characterized by determining the co-crystal structure of MuV-HN in complex with glycan receptors. Here, we describe protocols for large-scale expression, purification and crystallization of MuV-HN proteins for structural analyses and glycan-binding assays with the overarching goal of investigating glycan-protein interactions.

Computational protein design of an ensemble of conformations for one protein–i.e., multi-state design–determines the side chain identity by optimizing the energetic contributions of that side chain in each of the backbone conformations. Sampling the resulting large sequence-structure search space limits the number of conformations and the size of proteins in multi-state design algorithms. Here, we demonstrated that the REstrained CONvergence (RECON) algorithm can simultaneously evaluate the sequence of large proteins that undergo substantial conformational changes. Simultaneous optimization of side chain conformations across all conformations increased sequence conservation when compared to single-state designs in all cases. More importantly, the sequence space sampled by RECON MSD resembled the evolutionary sequence space of flexible proteins, particularly when confined to predicting the mutational preferences of limited common ancestral descent, such as in the case of influenza type A hemagglutinin. Additionally, we found that sequence positions which require substantial changes in their local environment across an ensemble of conformations are more likely to be conserved. These increased conservation rates are better captured by RECON MSD over multiple conformations and thus multiple local residue environments during design. To quantify this rewiring of contacts at a certain position in sequence and structure, we introduced a new metric designated ‘contact proximity deviation’ that enumerates contact map changes. This measure allows mapping of global conformational changes into local side chain proximity adjustments, a property not captured by traditional global similarity metrics such as RMSD or local similarity metrics such as changes in φ and ψ angles., Author summary Multi-state design can be used to engineer proteins that need to exist in multiple conformations or that bind to multiple partner molecules. In essence, multi-state design selects a compromise of protein sequences that allow for an ensemble of protein conformations, or states, associated with a particular biological function. In this paper, we used the REstrained CONvergence (RECON) algorithm with Rosetta to show that multi-state design of flexible proteins predicts sequences optimal for conformational change, mimicking mutation preferences sampled in evolution. Modeling optimal local side chain physicochemical environments within an ensemble selected significantly more native-like sequences than selections performed when all conformations states are designed independently. This outcome was particularly true for amino acids whose local side chain environment change between conformations. To quantify such contact map changes, we introduced a novel metric to show that sequence conservation is dependent on protein flexibility, i.e., changes in local side chain environments between stated limit the space of tolerated mutations. Additionally, such positions in sequence and structure are more likely to be energetically frustrated, at least in some states. Importantly, we showed that multi-state design over an ensemble of conformations (space) can explore evolutionary tolerated sequence space (time), thus enabling RECON to not only design proteins that require multiple states for function but also predict mutations that might be tolerated in native proteins but have not yet been explored by evolution. The latter aspect can be important to anticipate escape mutations, for example in pathogens or oncoproteins.

The cell surface is normally covered with sugars that are bound to lipids or proteins. Surface glycoproteins play critically important roles in many cellular events, including cell-cell communications, cell-matrix interactions, and response to environmental cues. Aberrant protein glycosylation on the cell surface is often a hallmark of human diseases such as cancer and infectious diseases. Global analysis of surface glycoproteins will result in a better understanding of glycoprotein functions and the molecular mechanisms of diseases and the discovery of surface glycoproteins as biomarkers and drug targets. Here, an enzyme is exploited to tag surface glycoproteins, generating a chemical handle for their selective enrichment prior to mass spectrometric (MS) analysis. The enzymatic reaction is very efficient, and the reaction conditions are mild, which are well-suited for surface glycoprotein tagging. For biologically triplicate experiments, on average 953 N-glycosylation sites on 393 surface glycoproteins per experiment were identified in MCF7 cells. Integrating chemical and enzymatic reactions with MS-based proteomics, the current method is highly effective to globally and site-specifically analyze glycoproteins only located on the cell surface. Considering the importance of surface glycoproteins, this method is expected to have extensive applications to advance glycoscience.

Hemagglutinin and neuraminidase, which constitute the glycoprotein spikes expressed on the surface of influenza A and B viruses, are the most exposed parts of the virus and play critical roles in the viral lifecycle. As such, they make prominent targets for the immune response and antiviral drugs. Neuraminidase inhibitors, particularly oseltamivir, constitute the most commonly used antivirals against influenza viruses, and they have proved their clinical utility against seasonal and emerging influenza viruses. However, the emergence of resistant strains remains a constant threat and consideration. Antivirals targeting the hemagglutinin protein are relatively new and have yet to gain global use but are proving to be effective additions to the antiviral repertoire, with a relatively high threshold for the emergence of resistance. Here we review antiviral drugs, both approved for clinical use and under investigation, that target the influenza virus hemagglutinin and neuraminidase proteins, focusing on their mechanisms of action and the emergence of resistance to them.

Two papers in Neuron provide compelling new indications of a link between herpesviruses and Alzheimer's disease (AD). Readhead et al. report an increased abundance of human herpesviruses 6A and 7 (HHV-6A/7) in AD brain, whereas Eimer et al. show that binding of the AD signature protein, Aβ, to herpes simplex virus type 1 (HSV-1) and HHV-6 surface glycoproteins causes fibrillar Aβ agglutination that can protect against viral challenge.

Galectins are animal lectins that bind to surface glycoproteins expressed at the fetal-maternal interface. The aim of this prospective case-control study was to investigate the possible relationship between levels of maternal serum galectin-7 and threatened abortion (TA) and to determine whether serum galectin-7 had any prognostic value.This prospective study was conducted between August 2014 and February 2015. Included in the study were 31 consecutive pregnant women who were hospitalized for TA between 6 and 14 weeks of gestation and 33 healthy gestational age matched pregnant women without any symptoms of miscarriage. Serum galectin-7 levels were measured via ELISA.The mean serum galectin-7 levels of the two groups were not significantly different (31 TA patients: 2.84 ± 0.43 pg/mL, 33 controls: 2.785 ± 0.32 pg/mL, p = 0.543). Six pregnancies in the TA group resulted in abortion (19.4%).Serum galectin-7 was not useful for predicting prognosis in TA.

Cadherins are surface glycoproteins on plasma membranes and exist in many forms: T-cadherin, neuronal cadherin (N-cadherin), epithelial cadherin (E-cadherin), and vascular endothelial (VE-cadherin). Cadherins play critical roles in cell–cell interactions and are involved in multiple functions related to cell growth and proliferation. Findings from numerous reports have indicated that VE-cadherin regulates the remodeling, gating, and maturation of vascular vessels. The surface morphology of materials also impacts endothelial cell adhesion. This report is an overview of recent research on the effects of cadherins on cell–cell interactions, along with cell adhesions as examined on different materials. This summary will provide novel insights and approaches for research on cell–cell and cell–material interactions and illuminate some of the mechanisms of cell growth on different materials.

The efficacy of some of the available antiretroviral drugs is very limited against HIV-2 and, most importantly, none of the current drugs effectively prevents entry into the cells. [...]

We report here the genome sequence of the influenza A virus strain A/swine/Siberia/1sw/2016, isolated from a swine in Russia. On the basis of sequence analysis, A/swine/Siberia/1sw/2016 is characterized by unusual surface glycoproteins phylogenetically distinct from those of swine A(H1N1)pdm09 influenza virus.

The parasitic African trypanosome, Trypanosoma brucei, evades the adaptive host immune response by a process of antigenic variation that involves the clonal switching of variant surface glycoproteins (VSGs). The VSGs that periodically come to dominate in vivo display a hierarchy, but how this hierarchy arises is not well-understood. Combining publicly available genetic data with mathematical modelling, we report a VSG-length-dependent hierarchical timing of clonal VSG dominance in a mouse model, revealing an inverse correlation between VSG length and trypanosome growth-rate. Our analysis indicates that, among parasites switching to new VSGs, those expressing shorter VSGs preferentially accumulate to a detectable level that is sufficient to trigger an effective immune response. Subsequent elimination of faster-growing parasites then allows slower parasites with longer VSGs to accumulate. This interaction between the host and parasite is able by itself to explain the temporal distribution of VSGs observed in vivo. Thus, our findings reveal a length-dependent hierarchy that operates during T. brucei infection, representing a ‘feint attack’ diversion tactic utilised during infection by these persistent parasites to out-maneuver the host immune system.Significance StatementThe protozoan parasite Trypanosoma brucei causes devastating and lethal diseases in humans and livestock. This parasite continuously evades the host adaptive immune response by drawing on a library of variant surface proteins but the mechanisms determining the timing of surface protein – host interactions are not understood. We report a simple mechanism, based on differential growth of parasites with surface proteins of different lengths, which can explain the hierarchy of variants over time. This allows parasites to evade host immune responses for extended timeframes using limited cohorts of surface proteins. We liken this strategy to a military ‘feint attack’, that enhances the parasites ability to evade the host immune response. A similar mechanism may also operate in other important pathogens.

Introduction: The acquired immunodeficiency syndrome (AIDS) is the culmination of the infection by the human immunodeficiency viruses upon destruction of CD4+ lymphocytes of the host [1]. The efficacy of the available antiretroviral drugs is very limited against HIV-2 and, most importantly, none of the current drugs effectively prevents entry into the cells. HIV envelope glycoproteins mediate binding to the receptor CD4 and co-receptors at the surface of the target cell, enabling fusion with the cell membrane and viral entry [2,3]. The discovery of multiple new hit compounds that can be used as useful starting points towards drug candidates for HIV-1 and HIV-2 therapy is the main goal of this work. The glycoproteins gp120 and gp125 are critical to the receptors recognition and internalization of viral material into the cell. The study aimed to assess if the modulation of the glycoproteins activity can lead to the disturbance of the entry viral mechanism. Materials and methods: Until now, it has been marked by the use of computational techniques to study the viral surface glycoproteins as potential drug targets against HIV-1 and HIV-2 infections. A 3D structure of HIV-2ROD gp125 was generated by homology modelling, using MOE2016 and MODELLER 9v19. Additionally, to disclose the importance of the main structural features and compare with experimental results, 3D-models of six V3 mutants were also generated using the C2V3C3 domain. Additionally, molecular dynamics is being performed, using Gromacs 2006.3, in order to better characterize this protein and disclose its the biological dynamic behaviour. The structures to use in molecular dynamic simulations were prepared using MOE 2016.0802 software and further exported as PDB files. Results: It is primordial to understand the structural behavior of these domains inserted in the main structure. These mutations revealed selectively impact in the behaviour of the protein. Structurally, the mutations studied leads to a loss of aromatic features, very important for the establishment of π-π interactions, which could induce a structural preference by a specific coreceptor. Discussion and conclusions: In the absence of a crystallographic structure of HIV-2 envelope gp125 comprising variable domains, computer aided modulation is crucial to identify structural features in the variable regions that correlate with HIV-2 tropism and susceptibility to neutralization, highly associated with the mutated residues. These new insights into the structure-function relationship will help in the design of better models and into the following of the design of new small molecules capable of use under the proposal presented inhibit the attachment and binding of HIV with host cells mediated by the envelope surface glycoproteins.

This research work provides comprehensive meaningful valuable findings from NCBI database for researches to analyze entries of H1N1 strains aiming to design genomic region-specific markers and also for screening the region-specific subtypes. Influenza A viruses are divided into subtypes, based on the nature of their surface glycoproteins, HA and NA. There are 16 different HAs and nine NAs which are distinguishable serologically, and we have sincerely dug NCBI database. We have found 7651 entries of H1N1 strains starting from the year 1918 till 2011 in the NCBI database, most recent entries from past few years includes, 1720 entries in the year 2008, 9112 entries in 2009, 1132 entries in 2010, 733 entries in 2011. Recent past few years has seen a rapid growth in high-throughput technology which has resulted in more entries accounting for 71.93% of the total entries in NCBI H1N1 Genome Database, in that, year 2009 which resulted in pandemic holds 51.62% share of the total H1N1 genome entries. 2009 entries were separated based on region of occurrence which resulted in 89 different regions. The above separation helps the researches for designing region-specific markers for screening the region-specific subtypes. Apart from that researches also get other key information like year of pandemic, subtypes responsible for pandemic, genes and virulence activity, genes functionality which can be used for genotyping.

Background Inherited platelet function disorders (IPFDs) are a wide spectrum of qualitative platelet disorders with variable bleeding tendency, ranging from mild bleeding to severe life-threatening episodes. Diagnosis and classification of IPFDs is a challenge worldwide. The present study aims to present a proper classification, describe the molecular basis and clinical presentations as well as some diagnostic clues for these disorders. Methods All relevant publications were searched using appropriate keywords. Results IPFDs can be divided into four major groups including defects of platelet surface glycoproteins, platelet granules and secretion disorders, platelet signaling defects, and transcription-related platelet disorders. Some of these disorders, such as Glanzman thrombasthenia, are more common, with severe bleeding, while most of these disorders are extremely rare with mild bleeding. Conclusions A proper classification, accompanied by familiarity with diagnostic clinical and laboratory features of IPFDs, can be helpful in in-time and exact diagnosis of these complicated bleeding disorders.

In order to deliver their genetic material to host cells during infection, enveloped viruses use specialized proteins on their surfaces that bind cellular receptors and induce fusion of the viral and host membranes. In paramyxoviruses, a diverse family of single-stranded RNA (ssRNA) viruses, including several important respiratory pathogens, such as parainfluenza viruses, the attachment and fusion machinery is composed of two separate proteins: a receptor binding protein (hemagglutinin-neuraminidase [HN]) and a fusion (F) protein that interact to effect membrane fusion. Here we used negative-stain and cryo-electron tomography to image the 3-dimensional ultrastructure of human parainfluenza virus 3 (HPIV3) virions in the absence of receptor engagement. We observed that HN exists in at least two organizations. The first were arrays of tetrameric HN that lacked closely associated F proteins: in these purely HN arrays, HN adopted a "heads-down" configuration. In addition, we observed regions of complex surface density that contained HN in an apparently extended "heads-up" form, colocalized with prefusion F trimers. This colocalization with prefusion F prior to receptor engagement supports a model for fusion in which HN in its heads-up state and F may interact prior to receptor engagement without activating F, and that interaction with HN in this configuration is not sufficient to activate F. Only upon receptor engagement by HN's globular head does HN transmit its activating signal to F.Human parainfluenza virus 3 (HPIV3) is an enveloped, ssRNA virus that can cause serious respiratory illness, especially in children. HPIV3, like most other paramyxoviruses, uses two specialized proteins to mediate cell entry: the fusion protein (F) and the receptor binding protein, hemagglutinin-neuraminidase (HN). F becomes activated to mediate fusion during entry when it is triggered by a signal from HN. Here we used electron tomography to reconstruct the 3-dimensional ultrastructure of HPIV3. From these structures, we could discern the distribution and, in some cases, conformation of HN and F proteins, which provided an understanding of their interrelationship on virions. HN is found in arrays alone in one conformation and interspersed with prefusion F trimers in another. The data support a model of paramyxovirus membrane fusion in which HN associates with F before receptor engagement, and receptor engagement by the globular head of HN switches the HN-F interaction into one of fusion activation.

In South American countries, bovine trypanosomiasis is caused mainly by Trypanosoma vivax. Among the infected animals, bovines are considered more susceptible, and this susceptibility varies among breeds. To determine the occurrence of T. vivax in Maranhão State, Brazil, a total of 559 cattle blood samples were collected for molecular and parasitological studies. On São Luís Island, no parasites were observed in the parasitological exam; however, with the polymerase chain reaction (PCR) method, three samples (1.06%) were positive. In four municipalities that compose the Pedreiras Basin, 3.39% of the animals were positive on the parasitological exam, and 6.21% of animals were positive by PCR. This finding demonstrates that PCR is more sensitive and confirms that the method is very useful in epidemiological surveys. A further interesting point is that molecular studies clearly define the differences in surface glycoproteins and antigenic variants.

Acquired thrombocytopenias represent a group of bleeding diseases which can be mediated by immune or non-immune factors. Acquired immune thrombocytopenia (AITP) leads to an accelerated decrease in platelet count by platelet reactive antibodies arising from several mechanisms. In AITP, autoantibodies (AAbs), alloantibodies or drug-dependent antibodies (DDAbs) are usually targeting platelet surface glycoproteins (GPs). The consequence of this is a significant decrease in the number of circulating platelets, leading to clinicopathological disorders including immune thrombocytopenia (ITP), heparin-induced thrombocytopenia (HIT) or drug-induced thrombocytopenia (DITP), respectively. The aforementioned disorders are characterized by a severe reduction in platelet count ( 9 /L) which is, with the exception of HIT, associated with high bleeding risk. In this review we provide current insight into recent achievements regarding pathophysiology, diagnosis and management of AITP.

In Saccharomyces cerevisiae , TBF1 , an essential gene, influences telomere function but also has other roles in the global regulation of transcription. We have identified a new member of the tbf1 gene family in the mammalian pathogen Pneumocystis carinii . We demonstrate by transspecies complementation that its ectopic expression can provide the essential functions of Schizosaccharomyces pombe tbf1 but that there is no rescue between fission and budding yeast orthologues. Our findings indicate that an essential function of this family of proteins has diverged in the budding and fission yeasts and suggest that effects on telomere length or structure are not the primary cause of inviability in S. pombe tbf1 null strains.

The study of human microbiota is an emerging research topic. The past efforts have mainly centered on studying the composition and genomic landscape of bacterial species within the targeted communities. The interaction between bacteria and hosts is the pivotal event in the initiation and progression of infectious diseases. There is a great need to identify and characterize the molecules that mediate the bacteria-host interaction. Bacterial surface exposed proteins play an important role in the bacteria- host interaction. Numerous surface proteins are glycosylated, and the glycosylation is crucial for their function in mediating the bacterial interaction with hosts. Here we present an overview of surface glycoproteins from bacteria that inhabit three major mucosal environments across human body: oral, gut and skin. We describe the important enzymes involved in the process of protein glycosylation, and discuss how the process impacts the bacteria-host interaction. Emerging molecular details underlying glycosylation of bacterial surface proteins may lead to new opportunities for designing anti-infective small molecules, and developing novel vaccines in order to treat or prevent bacterial infection.

Influenza is a rapidly mutating RNA virus causing mortality and morbidity in humans.The three different strains of influenza are characterized by different surface glycoproteins. Hemagglutinin (HA)...

Inherited deficiencies of platelet surface glycoproteins, such as Glanzmann thrombasthenia (GT), occasionally result in severe bleeding episodes. Platelet transfusion is considered standard therapy for securing hemostasis in subjects with GT when local measures and antifibrinolytic agents are inadequate. We describe 4 case studies which suggest that recombinant activated factor VII may be an effective alternative to platelet transfusion in preventing or controlling bleeding, including surgical bleeding, in patients with GT.

To deliver their genetic material into host cells, enveloped viruses have surface glycoproteins that actively cause the fusion of the viral and cellular membranes. Recently determined X-ray crystal structures of the paramyxovirus fusion (F) protein in its pre-fusion and post-fusion conformations reveal the dramatic structural transformation that this protein undergoes while causing membrane fusion. Conformational changes in key regions of the F protein suggest the mechanism by which the F protein is activated and refolds.

Previous analyses of HIV-1 surface glycoprotein indicate that both the V1/V2 region and the interaction of gp120 with CD4 influence the accessibility of the V3 region on gp120. In this study we investigated the accessibility of the V3 region of HIV-2 recombinant gp125 proteins using V3-specific mAbs (7C8 and 3C4) and analyzed the binding kinetics of soluble CD4 (sCD4) to recombinant HIV-1 gp120 and HIV-2 gp125 proteins by surface plasmon resonance (SPR) analysis. Our results indicated that 7C8 recognized monomers of gp125 and gp125Delta v1v2, (lacking the V1/V2 region) while 3C4 was sensitive to the conformation of gp125, recognizing only oligomers of gp125Delta v1v2. Furthermore, SPR analysis of 7C8 binding to gp125 demonstrated that the deletion of the V1/V2 region did not increase the accessibility of the V3 region in gp125Delta v1v2. Comparative SPR analyses of sCD4 binding HIV recombinant surface glycoproteins revealed a lower affinity of sCD4 to gp125 as compared to gp120. Moreover, the analyses suggest that conformational changes only occur in HIV-1 gp120 upon interaction with CD4. We hypothesize that the V3 region is accessible in HIV-2 gp125 and thus may not require interaction with CD4 to induce conformational reorientation of the V1/V2 region.

Evaluation of: Epstein SL: Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: an experiment of nature. J. Infect. Dis. 193, 49–53 (2006). Heterosubtypic immunity (HSI) to influenza A virus (IAV) occurs when some degree of protection to infection is afforded by prior infection with a different subtype of IAV (i.e., a strain with serologically non-crossreactive surface glycoproteins). The existence of HSI, although well-documented in mice, is uncertain in humans. In order to examine HSI in humans, Epstein retrieved data from the Cleveland Family Study, a study of 60 families with school-aged children. Importantly, these families were monitored for illness during 1947–1957, the end of which coincided with the Asian IAV pandemic caused by the introduction of the H2N2 strain into human populations. Culture-positive IAV infection rates were compared between adults and children. Interestingly, many more children became infected during the 1957 pandemic than adults (55 vs 17%). While previous IAV exposure during the 10-year study period provided protection against adult IAV infection in 1957 (only 5.6% were infected), no difference was observed in children previously infected with other subtypes of IAV (with 52% infected in 1957). Serum samples taken before the pandemic did not detectably interact with H2N2 glycoproteins, suggesting that factors other than virus-neutralizing antibodies provided HSI to adults. This re-evaluation of archived data provides an important demonstration of the possibility of HSI in humans. Improved knowledge of human HSI could lead to vaccines capable of limiting morbidity and mortality from future pandemic strains introduced into humans from animal reservoirs.

Breakthrough advances in the chemotherapy of influenza have been achieved in recent years and the approval of zanamivir (RelenzaTM, Biotech Holdings) by the United States FDA in July 1999 for the treatment of type A and type B influenza marked the first new influenza treatments since the approval of rimantadine in 1993. This was followed by the approval of oseltamivir (TamifluTM, Gilead Sciences) for the treatment of both type A and type B influenza in October 1999 and, subsequently, for the prevention of influenza A and B infection in adults and adolescents over the age of 13 years. Both zanamivir and oseltamivir are inhibitors of influenza neuraminidase, one of two surface glycoproteins of influenza virus and they represent a new class of anti-influenza agent. The successful launch of zanamivir and oseltamivir has prompted continued effort to discover and develop neuraminidase inhibitors with improved properties. Indeed, most of the anti-influenza drug discovery activity in recent years has been centred...

Multiplex PCR for simultaneous detection of Trypanosoma evansi and Theileria equi in single-step reaction was optimized and employed on 108 equids (99 horses and 9 donkeys/mules) blood samples collected from two agro-climatic zones (Sub-mountain undulating zone and Undulating plain zone) of Punjab to evaluate the status of concurrent infection and associated risk factors. The amplification products of 257 and 709 bp targeting repetitive nucleotide sequence of variable surface glycoproteins of T. evansi and 18S rRNA gene of T. equi, respectively expressed high fidelity of the primer pairs with sequence homology to neighboring geographic isolates. The overall prevalence of T. evansi and T. equi was 3.7 and 1.85%, with Undulating plain zone at higher infection risk for T. equi (OR = 3.24, 95% CI = 0.28–83.65); and Sub-mountain undulating zone (OR = ∞, 95% CI = 0.25–∞) for T. evansi. Multiplex PCR revealed higher risk of infection of both T. equi (OR = 6.75, 95% CI = 0.58–175.38) and T. evansi (OR = 2.11, 95% CI = 0.05–80.36) in the farms with inappropriate management system. The risk factor associated with the type of host species had an odds ratio of 12.35 (95% CI = 0.29–508.37) for donkeys/mules versus horses for T. evansi infection. This group was also at higher risk of infection with Odds ratio (OR) of 4 (95% CI = 0.14–53.99) for T. equi. The current investigation brings out various commodities at risk of infection pertaining to equid trypanosomosis and theileriosis evaluated by a rapid and sensitive multiplex PCR assay.

Galectins released by tumor cells and macrophages can bind surface glycoproteins of tumor-infiltrating lymphocytes (TILs), forming glycoprotein-galectin lattices with immunosuppressive activities. Specifically, TILs covered by galectin-3 are unable to secrete cytokines after stimulation. Treating TILs ex vivo with galectin antagonists for a few hours boosts their functions. Several galectin antagonists are currently available for clinical trials.