scholarly journals Singapore grouper iridovirus-encoded semaphorin homologue (SGIV-sema) contributes to viral replication, cytoskeleton reorganization and inhibition of cellular immune responses

2014 ◽  
Vol 95 (5) ◽  
pp. 1144-1155 ◽  
Author(s):  
Yang Yan ◽  
Huachun Cui ◽  
Chuanyu Guo ◽  
Jingguang Wei ◽  
Youhua Huang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Replication ◽  
Host Cells ◽  
Early Gene ◽  
Coding Region ◽  
Cytoskeletal Structure ◽  
Wide Range ◽  
Fish Cells ◽  
Cellular Immune

Semaphorins are a large, phylogenetically conserved family of proteins that are involved in a wide range of biological processes including axonal steering, organogenesis, neoplastic transformation, as well as immune responses. In this study, a novel semaphorin homologue gene belonging to the Singapore grouper iridovirus (SGIV), ORF155R (termed SGIV-sema), was cloned and characterized. The coding region of SGIV-sema is 1728 bp in length, encoding a predicted protein with 575 aa. SGIV-sema contains a ~370 aa N-terminal Sema domain, a conserved plexin-semaphorin-integrin (PSI) domain, and an immunoglobulin (Ig)-like domain near the C terminus. SGIV-sema is an early gene product during viral infection and predominantly distributed in the cytoplasm with a speckled and clubbed pattern of appearance. Functionally, SGIV-sema could promote viral replication during SGIV infection in vitro, with no effect on the proliferation of host cells. Intriguingly, ectopically expressed SGIV-sema could alter the cytoskeletal structure of fish cells, characterized by a circumferential ring of microtubules near the nucleus and a disrupted microfilament organization. Furthermore, SGIV-sema was able to attenuate the cellular immune response, as demonstrated by decreased expression of inflammation/immune-related genes such as IL-8, IL-15, TNF-α and mediator of IRF3 activation (MITA), in SGIV-sema-expressing cells before and after SGIV infection. Ultimately, our study identified a novel, functional SGIV gene that could regulate cytoskeletal structure, immune responses and facilitate viral replication.

MIP-1α and MIP-1β differentially mediate mucosal and systemic adaptive immunity

Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 807-814 ◽  
Author(s):  
James W. Lillard ◽  
Udai P. Singh ◽  
Prosper N. Boyaka ◽  
Shailesh Singh ◽  
Dennis D. Taub ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Cd8 T Cells ◽  
Host Cells ◽  
Secretory Iga ◽  
Specific Cell ◽  
Cellular Immune Responses ◽  
Cc Chemokines ◽  
Cellular Immune

AbstractMacrophage inflammatory protein-1α (MIP-1α) and MIP-1β are distinct but highly homologous CC chemokines produced by a variety of host cells in response to various external stimuli and share affinity for CCR5. To better elucidate the role of these CC chemokines in adaptive immunity, we have characterized the affects of MIP-1α and MIP-1β on cellular and humoral immune responses. MIP-1α stimulated strong antigen (Ag)–specific serum immunoglobulin G (IgG) and IgM responses, while MIP-1β promoted lower IgG and IgM but higher serum IgA and IgE antibody (Ab) responses. MIP-1α elevated Ag-specific IgG1 and IgG2b followed by IgG2a and IgG3 subclass responses, while MIP-1β only stimulated IgG1 and IgG2b subclasses. Correspondingly, MIP-1β produced higher titers of Ag-specific mucosal secretory IgA Ab levels when compared with MIP-1α. Splenic T cells from MIP-1α– or MIP-1β–treated mice displayed higher Ag-specific Th1 (interferon-γ [IFN-γ]) as well as selective Th2 (interleukin-5 [IL-5] and IL-6) cytokine responses than did T cells from control groups. Interestingly, mucosally derived T cells from MIP-1β–treated mice displayed higher levels of IL-4 and IL-6 compared with MIP-1α–treated mice. However, MIP-1α effectively enhanced Ag-specific cell-mediated immune responses. In correlation with their selective effects on humoral and cellular immune responses, these chemokines also differentially attract CD4+ versus CD8+ T cells and modulate CD40, CD80, and CD86 expressed by B220+ cells as well as CD28, 4-1BB, and gp39 expression by CD4+ and CD8+ T cells in a dose-dependent fashion. Taken together, these studies suggest that these CC chemokines differentially enhance mucosal and serum humoral as well as cellular immune responses.

scholarly journals Salmonella Adhesion, Invasion and Cellular Immune Responses Are Differentially Affected by Iron Concentrations in a Combined In Vitro Gut Fermentation-Cell Model

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e93549 ◽  
Author(s):  
Alexandra Dostal ◽  
Mélanie Gagnon ◽  
Christophe Chassard ◽  
Michael Bruce Zimmermann ◽  
Liam O'Mahony ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Model ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Gut Fermentation ◽  
Iron Concentrations

scholarly journals Osteopontin and iCD8α cells promote intestinal intraepithelial lymphocyte homeostasis

2019 ◽  
Author(s):  
Ali Nazmi ◽  
Michael J. Greer ◽  
Kristen L. Hoek ◽  
M. Blanca Piazuelo ◽  
Joern-Hendrik Weitkamp ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Inflammation ◽  
Intraepithelial Lymphocytes ◽  
Intestinal Lumen ◽  
Anatomical Location ◽  
List Type ◽  
Intestinal Intraepithelial Lymphocyte ◽  
Critical Components ◽  
Cellular Immune

AbstractIntestinal intraepithelial lymphocytes (IEL) comprise a diverse population of cells residing in the epithelium at the interface between the intestinal lumen and the sterile environment of the lamina propria. Because of this anatomical location, IEL are considered critical components of intestinal immune responses. Indeed, IEL are involved in many different immunological processes ranging from pathogen control to tissue stability. However, despite their critical importance in mucosal immune responses, very little is known about the homeostasis of different IEL subpopulations. The phosphoprotein osteopontin is important for critical physiological processes, including cellular immune responses such as survival of Th17 cells and homeostasis of NK cells, among others. Because of its impact in the immune system, we investigated the role of osteopontin in the homeostasis of IEL. Here, we report that mice deficient in the expression of osteopontin exhibit reduced numbers of the IEL subpopulations TCRγδ+, TCRβ+CD4+, TCRβ+CD4+CD8α+and TCRβ+CD8αα+cells in comparison to wild-type mice. For some IEL subpopulations the decrease in cells numbers could be attributed to apoptosis and reduced cell division. Moreover, we showin vitrothat exogenous osteopontin stimulates the survival of murine IEL subpopulations and unfractionated IEL derived from human intestines, an effect mediated by CD44, a known osteopontin receptor. We also show that iCD8α IEL, but not TCRγδ+IEL, TCRβ+IEL or intestinal epithelial cells, can promote survival of different IEL populations via osteopontin, indicating an important role for iCD8α cells in the homeostasis of IEL.Key PointsOsteopontin promotes homeostasis of mouse and human IEL, mediated by its ligand CD44iCD8α cells produce osteopontin which impacts the survival of other IELLack of osteopontin renders mice susceptible to intestinal inflammation

scholarly journals A Combined Adjuvant TF–Al Consisting of TFPR1 and Aluminum Hydroxide Augments Strong Humoral and Cellular Immune Responses in Both C57BL/6 and BALB/c Mice

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1408
Author(s):  
Qiao Li ◽  
Zhihua Liu ◽  
Yi Liu ◽  
Chen Liang ◽  
Jiayi Shu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Inbred Mouse ◽  
Effective Vaccine ◽  
Mouse Strains ◽  
Cellular Immune Responses ◽  
Recombinant Hbsag ◽  
Cellular Immune

TFPR1 is a novel adjuvant for protein and peptide antigens, which has been demonstrated in BALB/c mice in our previous studies; however, its adjuvanticity in mice with different genetic backgrounds remains unknown, and its adjuvanticity needs to be improved to fit the requirements for various vaccines. In this study, we first compared the adjuvanticity of TFPR1 in two commonly used inbred mouse strains, BALB/c and C57BL/6 mice, in vitro and in vivo, and demonstrated that TFPR1 activated TLR2 to exert its immune activity in vivo. Next, to prove the feasibility of TFPR1 acting as a major component of combined adjuvants, we prepared a combined adjuvant, TF–Al, by formulating TFPR1 and alum at a certain ratio and compared its adjuvanticity with that of TFPR1 and alum alone using OVA and recombinant HBsAg as model antigens in both BALB/c and C57BL/6 mice. Results showed that TFPR1 acts as an effective vaccine adjuvant in both BALB/c mice and C57BL/6 mice, and further demonstrated the role of TLR2 in the adjuvanticity of TFPR1 in vivo. In addition, we obtained a novel combined adjuvant, TF–Al, based on TFPR1, which can augment antibody and cellular immune responses in mice with different genetic backgrounds, suggesting its promise for vaccine development in the future.

scholarly journals Cytokine Profiles and Cell Proliferation Responses to Truncated ORF2 Protein in Iranian Patients Recovered from Hepatitis E Infection

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Reza Taherkhani ◽  
Fatemeh Farshadpour ◽  
Manoochehr Makvandi ◽  
Hamid Rajabi Memari ◽  
Ali Reza Samarbafzadeh ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Hepatitis E ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Orf2 Protein ◽  
Cellular Immune ◽  
Iranian Patients

Background.The aim of this study was to evaluatehepatitis E virus(HEV) specific cellular immune responses to truncated ORF2 protein in Iranian patients recovered from HEV infection. Information about HEV-specific immune responses could be useful in finding an effective way for development of HEV vaccine.Methods.A truncated form of HEV ORF2 protein containing amino acids 112-608 was used to stimulate peripheral blood mononuclear cells (PBMCs) separated from HEV-recovered and control groups. Finally, the levels of four cytokines, IFN-γELISPOT, and cell proliferative responses following stimulation with the truncated ORF2 protein were assessed in the both groups.Results.The truncated ORF2 protein was able to induce IFN-γELISPOT and cell proliferation responses and to produce significant amounts of IFN-γand IL-12 cytokines, but low amounts of IL-10 and IL-4 cytokinesin vitro. These responses were significantly higher in the recovered group compared to the control group. These results indicate the antigenic nature of the truncated ORF2 protein and production of T helper type 1 cytokines.Conclusion.The truncated ORF2 protein can effectively induce significant cellular immune responsesand can be introduced as a potential vaccine candidate. However, further studies are required to evaluate this proteinin vivo.

scholarly journals STAT2-Dependent Immune Responses Ensure Host Survival despite the Presence of a Potent Viral Antagonist

2018 ◽  
Vol 92 (14) ◽  
Author(s):  
Vu Thuy Khanh Le-Trilling ◽  
Kerstin Wohlgemuth ◽  
Meike U. Rückborn ◽  
Andreja Jagnjic ◽  
Fabienne Maaßen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Replication ◽  
Mutual Influence ◽  
Type I ◽  
Mcmv Infection ◽  
General Importance ◽  
Interferon Antagonism ◽  
Deficient Mice

ABSTRACTA pathogen encounter induces interferons, which signal via Janus kinases and STAT transcription factors to establish an antiviral state. However, the host and pathogens are situated in a continuous arms race which shapes host evolution toward optimized immune responses and the pathogens toward enhanced immune-evasive properties. Mouse cytomegalovirus (MCMV) counteracts interferon responses by pM27-mediated degradation of STAT2, which directly affects the signaling of type I as well as type III interferons. Using MCMV mutants lackingM27and mice lacking STAT2, we studied the opposing relationship between antiviral activities and viral antagonism in a natural host-pathogen pairin vitroandin vivo. In contrast to wild-type (wt) MCMV, ΔM27 mutant MCMV was efficiently cleared from all organs within a few days in BALB/c, C57BL/6, and 129 mice, highlighting the general importance of STAT2 antagonism for MCMV replication. Despite this effective and relevant STAT2 antagonism, wt and STAT2-deficient mice exhibited fundamentally different susceptibilities to MCMV infections. MCMV replication was increased in all assessed organs (e.g., liver, spleen, lungs, and salivary glands) of STAT2-deficient mice, resulting in mortality during the first week after infection. Taken together, the results of our study reveal the importance of cytomegaloviral interferon antagonism for viral replication as well as a pivotal role of the remaining STAT2 activity for host survival. This mutual influence establishes a stable evolutionary standoff situation with fatal consequences when the equilibrium is disturbed.IMPORTANCEThe host limits viral replication by the use of interferons (IFNs), which signal via STAT proteins. Several viruses evolved antagonists targeting STATs to antagonize IFNs (e.g., cytomegaloviruses, Zika virus, dengue virus, and several paramyxoviruses). We analyzed infections caused by MCMV expressing or lacking the STAT2 antagonist pM27 in STAT2-deficient and control mice to evaluate its importance for the host and the virusin vitroandin vivo. The inability to counteract STAT2 directly translates into exaggerated IFN susceptibilityin vitroand pronounced attenuationin vivo. Thus, the antiviral activity mediated by IFNs via STAT2-dependent signaling drove the development of a potent MCMV-encoded STAT2 antagonist which became indispensable for efficient virus replication and spread to organs required for dissemination. Despite this clear impact of viral STAT2 antagonism, the host critically required the remaining STAT2 activity to prevent overt disease and mortality upon MCMV infection. Our findings highlight a remarkably delicate balance between host and virus.

scholarly journals Efficient and Stable Delivery of Multiple Genes to Fish Cells by a Modified Recombinant Baculovirus System

2018 ◽  
Vol 19 (12) ◽  
pp. 3767 ◽  
Author(s):  
Qian Wang ◽  
Jian Fang ◽  
Qihua Pan ◽  
Yizhou Wang ◽  
Ting Xue ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Fluorescent Protein ◽  
Recombinant Baculovirus ◽  
Transgenic Fish ◽  
Early Gene ◽  
Drug Selection ◽  
Baculovirus System ◽  
Fish Cells

The recombinant baculovirus has been widely used as an efficient tool to mediate gene delivery into mammalian cells but has barely been used in fish cells. In the present study, we constructed a recombinant baculovirus containing the dual-promoter cytomegalovirus (CMV) and white spot syndrome virus (WSSV) immediate-early gene 1 (ie1) (WSSV ie1), followed by a puromycin–green fluorescent protein (Puro-GFP, pf) or puromycin–red fluorescent protein (Puro-RFP, pr) cassette, which simultaneously allowed for easy observation, rapid titer determination, drug selection, and exogenous gene expression. This recombinant baculovirus was successfully transduced into fish cells, including Mylopharyngodon piceus bladder (MPB), fin (MPF), and kidney (MPK); Oryzias latipes spermatogonia (SG3); and Danio rerio embryonic fibroblast (ZF4) cells. Stable transgenic cell lines were generated after drug selection, which was further verified by Western blot. A cell monoclonal formation assay proved the stable heredity of transgenic MPB cells. In addition, a recombinant baculovirus containing a pr cassette and four transcription factors for induced pluripotent stem cells (iPSC) was constructed and transduced into ZF4 cells, and these exogenous genes were simultaneously delivered and transcribed efficiently in drug-selected ZF4 cells, proving the practicability of this modified recombinant baculovirus system. We also proved that the WSSV ie1 promoter had robust activity in fish cells in vitro and in vivo. Taken together, this modified recombinant baculovirus can be a favorable transgenic tool to obtain transient or stable transgenic fish cells.

scholarly journals Genetic Analysis of the Pestivirus Nonstructural Coding Region: Defects in the NS5A Unit Can Be Complemented intrans

2001 ◽  
Vol 75 (17) ◽  
pp. 7791-7802 ◽  
Author(s):  
Claus W. Grassmann ◽  
Olaf Isken ◽  
Norbert Tautz ◽  
Sven-Erik Behrens
Keyword(s):  
Viral Replication ◽  
Proteolytic Processing ◽  
Host Cells ◽  
Molar Ratio ◽  
Replication Capacity ◽  
Coding Region ◽  
Positive Strand ◽  
Reading Frame ◽  
Diarrhea Virus ◽  
Positive Strand Rna

ABSTRACT The functional analysis of molecular determinants which control the replication of pestiviruses was considerably facilitated by the finding that subgenomic forms of the positive-strand RNA genome of BVDV (bovine viral diarrhea virus) are capable of autonomous replication in transfected host cells. The prototype replicon, BVDV DI9c, consists of the genomic 5′ and 3′ untranslated regions and a truncated open reading frame (ORF) encoding mainly the nonstructural proteins NS3, NS4A, NS4B, NS5A, and NS5B. To gain insight into which of these proteins are essential for viral replication and whether they act in cisor in trans, we introduced a large spectrum of in-frame mutations into the DI9c ORF. Tests of the mutant RNAs in terms of their replication capacity and their ability to support translation and cleavage of the nonstructural polyprotein, and whether defects could be rescued in trans, yielded the following results. (i) RNA replication was found to be dependent on the expression of each of the DI9c-encoded mature proteins NS3 to NS5B (and the known associated enzymatic activities). In the same context, a finely balanced molar ratio of the diverse proteolytic processing products was indicated to be crucial for the formation of an active catalytic replication complex. (ii) Synthesis of negative-strand intermediate and progeny positive-strand RNA was observed to be strictly coupled with all functional DI9c ORF derivatives. NS3 to NS5B were hence suggested to play a pivotal role even during early steps of the viral replication pathway. (iii) Mutations in the NS3 and NS4B units which generated nonfunctional or less functional RNAs were determined to becis dominant. Likewise, lethal alterations in the NS4A and NS5B regions were invariably noncomplementable. (iv) In surprising contrast, replication of functional and nonfunctional NS5A mutants could be clearly enhanced and restored, respectively. In summary, our data provide initial insights into the organization of the pestivirus replication machinery.

Cellular immune responses to autologous chronic myelogenous leukaemia cells in vitro

1996 ◽  
Vol 42 (3) ◽  
pp. 193-199 ◽  
Author(s):  
Graham Pawelec ◽  
Arnika Rehbein ◽  
Elke Schlotz ◽  
Paul da Silva
Keyword(s):  
Immune Responses ◽  
Chronic Myelogenous Leukaemia ◽  
Myelogenous Leukaemia ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Novel Intersubunit Interaction Critical for HIV-1 Core Assembly Defines a Potentially Targetable Inhibitor Binding Pocket

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Pierrick Craveur ◽  
Anna T. Gres ◽  
Karen A. Kirby ◽  
Dandan Liu ◽  
John A. Hammond ◽  
...  
Keyword(s):  
Viral Replication ◽  
Specific Interaction ◽  
Binding Pocket ◽  
Core Stability ◽  
Host Cells ◽  
Capsid Assembly ◽  
Dynamic Simulations ◽  
Virus Like Particle ◽  
Hiv 1

ABSTRACTHIV-1 capsid protein (CA) plays critical roles in both early and late stages of the viral replication cycle. Mutagenesis and structural experiments have revealed that capsid core stability significantly affects uncoating and initiation of reverse transcription in host cells. This has led to efforts in developing antivirals targeting CA and its assembly, although none of the currently identified compounds are used in the clinic for treatment of HIV infection. A specific interaction that is primarily present in pentameric interfaces in the HIV-1 capsid core was identified and is reported to be important for CA assembly. This is shown by multidisciplinary characterization of CA site-directed mutants using biochemical analysis of virus-like particle formation, transmission electron microscopy ofin vitroassembly, crystallographic studies, and molecular dynamic simulations. The data are consistent with a model where a hydrogen bond between CA residues E28 and K30′ from neighboring N-terminal domains (CANTDs) is important for CA pentamer interactions during core assembly. This pentamer-preferred interaction forms part of anN-terminaldomaininterface (NDI) pocket that is amenable to antiviral targeting.IMPORTANCEPrecise assembly and disassembly of the HIV-1 capsid core are key to the success of viral replication. The forces that govern capsid core formation and dissociation involve intricate interactions between pentamers and hexamers formed by HIV-1 CA. We identified one particular interaction between E28 of one CA and K30′ of the adjacent CA that appears more frequently in pentamers than in hexamers and that is important for capsid assembly. Targeting the corresponding site could lead to the development of antivirals which disrupt this interaction and affect capsid assembly.

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