scholarly journals C Proteins: Controllers of Orderly Paramyxovirus Replication and of the Innate Immune Response

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 137
Author(s):  
Oliver Siering ◽  
Roberto Cattaneo ◽  
Christian K. Pfaller
Keyword(s):  
Innate Immune ◽  
Particle Assembly ◽  
Amino Acid Homology ◽  
Cytoplasmic Proteins ◽  
Structure Conservation ◽  
Natural Hosts ◽  
C Proteins ◽  
Alternative Reading Frames ◽  
Transformed Cell Lines ◽  
Phosphoprotein Gene

Particles of many paramyxoviruses include small amounts of proteins with a molecular weight of about 20 kDa. These proteins, termed “C”, are basic, have low amino acid homology and some secondary structure conservation. C proteins are encoded in alternative reading frames of the phosphoprotein gene. Some viruses express nested sets of C proteins that exert their functions in different locations: In the nucleus, they interfere with cellular transcription factors that elicit innate immune responses; in the cytoplasm, they associate with viral ribonucleocapsids and control polymerase processivity and orderly replication, thereby minimizing the activation of innate immunity. In addition, certain C proteins can directly bind to, and interfere with the function of, several cytoplasmic proteins required for interferon induction, interferon signaling and inflammation. Some C proteins are also required for efficient virus particle assembly and budding. C-deficient viruses can be grown in certain transformed cell lines but are not pathogenic in natural hosts. C proteins affect the same host functions as other phosphoprotein gene-encoded proteins named V but use different strategies for this purpose. Multiple independent systems to counteract host defenses may ensure efficient immune evasion and facilitate virus adaptation to new hosts and tissue environments.

scholarly journals Innate Immune Defenses Induced by CpG Do Not Promote Vaccine-Induced Protection against Foot-and-Mouth Disease Virus in Pigs

2009 ◽  
Vol 16 (8) ◽  
pp. 1151-1157 ◽  
Author(s):  
M. P. Alves ◽  
L. Guzylack-Piriou ◽  
V. Juillard ◽  
J.-C. Audonnet ◽  
T. Doel ◽  
...  
Keyword(s):  
Disease Virus ◽  
Large Scale ◽  
Control Strategies ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Innate Immune ◽  
Noticeable Effect ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Natural Hosts

ABSTRACT Emergency vaccination as part of the control strategies against foot-and-mouth disease virus (FMDV) has the potential to limit virus spread and reduce large-scale culling. To reduce the time between vaccination and the onset of immunity, immunostimulatory CpG was tested for its capacity to promote early protection against FMDV challenge in pigs. To this end, CpG 2142, an efficient inducer of alpha interferon, was injected intramuscularly. Increased transcription of Mx1, OAS, and IRF-7 was identified as a sensitive measurement of CpG-induced innate immunity, with increased levels detectable to at least 4 days after injection of CpG formulated with Emulsigen. Despite this, CpG combined with an FMD vaccine did not promote protection. Pigs vaccinated 2 days before challenge had disease development, which was at least as acute as that of unvaccinated controls. All pigs vaccinated 7 days before challenge were protected without a noticeable effect of CpG. In summary, our results demonstrate the caution required when translating findings from mouse models to natural hosts of FMDV.

scholarly journals A30 DIFFERENCES BETWEEN HUMAN AND MOUSE INTESTINAL EPITHELIAL CELLS IN THEIR INNATE IMMUNE RESPONSES TO BACTERIAL AND HOST STIMULI.

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 2-3
Author(s):  
J M Allaire ◽  
A Poon ◽  
S M Crowley ◽  
X Han ◽  
M Stahl ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Inflammatory Responses ◽  
Intestinal Epithelial Cells ◽  
Innate Immune ◽  
Negative Regulator ◽  
Intestinal Epithelial ◽  
Innate Immune Responses ◽  
Transformed Cell Lines ◽  
First Time

Abstract Background Intestinal epithelial cells (IEC) reside in close contact with the gut microbiota. It is thus important that IEC are hypo-responsive to bacterial products to prevent maladaptive inflammatory responses in the gut, such as those seen in Inflammatory bowel diseases (IBD). This suppression of innate immune signaling in IEC is in part due to their strong expression of Single Ig IL1 related receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and toll-like receptor (TLR) signaling. IL37, a newly recognized anti-inflammatory cytokine has been shown to strongly inhibit innate signaling in cells by binding to, and signaling through SIGIRR, leading to suppression of various forms of inflammation in mice. Few studies have looked at the function of IL-37/SIGIRR in IEC and their potential use to balance inflammatory responses. Notably, while many groups have studied IEC immune response in vitro, using transformed IEC lines, our focus is on primary-derived IEC which more accurately reflect in vivo responses. Aims To characterize IEC intrinsic and species-specific immune responses elicited by bacteria and host products as well as the role of IL37/SIGIRR in regulating this innate signaling. Methods We used organoid to study the innate immune responses of primary IEC derived from human or mouse colon (colonoids). After stimulation with inflammatory stimuli (IL1β, FliC and LPS), qPCR, ELISA, Milliplex Multiplex Assay and Western blot were used to determine modification in signalling pathway and cytokine/chemokine secretion. Results Using colonoids derived from healthy donors, we demonstrated that unlike transformed cell lines or mouse IEC, human IEC respond only to the bacterial product FliC, and not to LPS or IL1β. We further characterized human colonoid innate immune responses and despite significant inter-individual variability upon FliC stimulation, all organoids released several chemokines (IL8, CXCL1, CXCL2, CCL2 and CCL20). We showed for the first time that IL37 attenuated these innate immune responses through inhibition of intracellular signaling pathways (p38 and NFkB). Using colonoids derived from wildtype and Sigirr deficient mice, we found that mice IEC were responsive to IL1b and FliC and that the suppressive effects of IL37 were Sigirr dependent. Conclusions Our results show that human IEC show variability among individuals in the magnitude of their innate immune responses, and these responses differ from those obtained from transformed cells and primary mouse IEC. For the first time, we show that IL37 suppresses IEC innate immune responses, through its ability to signal through Sigirr. Further investigations will assess the ability of IL37 to control inflammation of IEC derived from IBD patients, as a potential therapeutic to promote gut health. Funding Agencies CAG, CIHRMSFHR

scholarly journals Recent advances in the understanding of Nipah virus immunopathogenesis and anti-viral approaches

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1763 ◽  
Author(s):  
Rodolphe Pelissier ◽  
Mathieu Iampietro ◽  
Branka Horvat
Keyword(s):  
Immune Response ◽  
Mammalian Species ◽  
Nipah Virus ◽  
Innate Immune ◽  
Type I ◽  
Therapeutic Approaches ◽  
Viral Spread ◽  
Adaptive Immune ◽  
Severe Acute Respiratory Infection ◽  
Natural Hosts

Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus that emerged at the end of last century as a human pathogen capable of causing severe acute respiratory infection and encephalitis. Although NiV provokes serious diseases in numerous mammalian species, the infection seems to be asymptomatic in NiV natural hosts, the fruit bats, which provide a continuous virus source for further outbreaks. Consecutive human-to-human transmission has been frequently observed during outbreaks in Bangladesh and India. NiV was shown to interfere with the innate immune response and interferon type I signaling, restraining the anti-viral response and permitting viral spread. Studies of adaptive immunity in infected patients and animal models have suggested an unbalanced immune response during NiV infection. Here, we summarize some of the recent studies of NiV pathogenesis and NiV-induced modulation of both innate and adaptive immune responses, as well as the development of novel prophylactic and therapeutic approaches, necessary to control this highly lethal emerging infection.

scholarly journals Nucleocytoplasmic Trafficking Perturbation Induced by Picornaviruses

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1210
Author(s):  
Belén Lizcano-Perret ◽  
Thomas Michiels
Keyword(s):  
Immune Responses ◽  
Nuclear Pore Complex ◽  
Viral Genome ◽  
Nuclear Translocation ◽  
Innate Immune ◽  
Nuclear Pore ◽  
Innate Immune Responses ◽  
Nucleocytoplasmic Trafficking ◽  
Host Proteins ◽  
Cytoplasmic Proteins

Picornaviruses are positive-stranded RNA viruses. Even though replication and translation of their genome take place in the cytoplasm, these viruses evolved different strategies to disturb nucleocytoplasmic trafficking of host proteins and RNA. The major targets of picornavirus are the phenylalanine-glycine (FG)-nucleoporins, which form a mesh in the central channel of the nuclear pore complex through which protein cargos and karyopherins are actively transported in both directions. Interestingly, while enteroviruses use the proteolytic activity of their 2A protein to degrade FG-nucleoporins, cardioviruses act by triggering phosphorylation of these proteins by cellular kinases. By targeting the nuclear pore complex, picornaviruses recruit nuclear proteins to the cytoplasm, where they increase viral genome translation and replication; they affect nuclear translocation of cytoplasmic proteins such as transcription factors that induce innate immune responses and retain host mRNA in the nucleus thereby preventing cell emergency responses and likely making the ribosomal machinery available for translation of viral RNAs.

scholarly journals Protein migration into nuclei. II. Frog oocyte nuclei accumulate a class of microinjected oocyte nuclear proteins and exclude a class of microinjected oocyte cytoplasmic proteins.

1975 ◽  
Vol 64 (2) ◽  
pp. 431-437 ◽  
Author(s):  
W M Bonner
Keyword(s):  
Gel Electrophoresis ◽  
Xenopus Oocytes ◽  
Sodium Dodecyl ◽  
Oocyte Nucleus ◽  
Cytoplasmic Proteins ◽  
Frog Oocyte ◽  
C Proteins ◽  
Oocyte Nuclear Proteins ◽  
Donor Oocytes ◽  
N Proteins

Nuclear contents or cytoplasm from Xenopus oocytes labeled with (35-S)methionine or (3-H)proline (donor oocytes) were reinjected into unlabeled oocytes (recipient oocytes). The radioactivity injected as nuclear contents was found to enter and accumulate in the recipient oocyte nucleus. In contrast, the radioactivity injected as cytoplasm was found to enter but not to accumulate in the recipient oocyte nucleus. Sodium dodecyl sulfate (SDS) gel electrophoresis of the nucleus and cytoplasm of donor oocytes revealed the existence of three classes of labeled proteins in these oocytes: those proteins found predominantly in the nucleus (N proteins), those found predominantly in the cytoplasm (C proteins), and those found in both the nucleus and cytoplasm at similar concentrations (B proteins). SDS gel electrophoresis of the nucleus and cytoplasm of recipient oocytes showed that N proteins entered and accumulated in the nucleus but that B proteins partitioned about equally between the nucleus and cytoplasm. A similar analysis of oocytes injected with labeled cytoplasm showed that C proteins did not enter the nucleus but again B proteins partitioned about equally between the nucleus and cytoplasm.

scholarly journals Neutrophil Extracellular Traps in Colorectal Cancer Progression and Metastasis

2021 ◽  
Vol 22 (14) ◽  
pp. 7260
Author(s):  
Umama Khan ◽  
Sabrina Chowdhury ◽  
Md Morsaline Billah ◽  
Kazi Mohammed Didarul Islam ◽  
Henrik Thorlacius ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Progression ◽  
Neutrophil Extracellular Traps ◽  
Gastrointestinal Diseases ◽  
Innate Immune ◽  
Regulatory Mechanisms ◽  
Extracellular Traps ◽  
Cytoplasmic Proteins ◽  
Colorectal Cancer Progression

Neutrophils form sticky web-like structures known as neutrophil extracellular traps (NETs) as part of innate immune response. NETs are decondensed extracellular chromatin filaments comprising nuclear and cytoplasmic proteins. NETs have been implicated in many gastrointestinal diseases including colorectal cancer (CRC). However, the regulatory mechanisms of NET formation and potential pharmacological inhibitors in the context of CRC have not been thoroughly discussed. In this review, we intend to highlight roles of NETs in CRC progression and metastasis as well as the potential of targeting NETs during colon cancer therapy.

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