Simian virus 40 (SV40) is a monkey virus with tumorigenic potential in rodents and is associated with several types of human cancers, including lymphomas. A related Merkel cell polyomavirus causes carcinoma in humans by expressing truncated large tumor antigen (LT), with truncations caused by APOBEC family of cytidine deaminase-induced mutations. AID (activation-induced cytidine deaminase), a member of the APOBEC family, is the initiator of the antibody diversification process known as somatic hypermutation and its aberrant expression and targeting is a frequent source of lymphomagenesis. In this study, we investigated whether AID could cause mutations in SV40 LT. We demonstrate that the SV40 enhancer has strong somatic hypermutation targeting activity in several cell types and that AID-induced mutations accumulate in SV40 LT in B cells and kidney cells and cause truncated LT expression in B cells. Our results argue that the ability of the SV40 enhancer to target somatic hypermutation to LT is a potential source of LT truncation events that could contribute to tumorigenesis in various cell types, thereby linking SV40 infection with malignant development through a novel mutagenic pathway.
- MeSH
- AICDA (aktivací indukovaná cytidindeamináza) MeSH
- antigeny transformující polyomavirové genetika metabolismus MeSH
- antigeny virové nádorové genetika metabolismus MeSH
- B-lymfocyty virologie metabolismus imunologie MeSH
- buněčné linie MeSH
- cytidindeaminasa * genetika metabolismus MeSH
- infekce onkogenními viry genetika virologie MeSH
- karcinogeneze genetika MeSH
- lidé MeSH
- mutace MeSH
- opičí virus SV40 * genetika MeSH
- polyomavirové infekce genetika virologie MeSH
- somatická hypermutace imunoglobulinových genů genetika MeSH
- zesilovače transkripce * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- biologické markery analýza krev MeSH
- hepatitida B - antigeny analýza krev MeSH
- hepatitida B - protilátky * analýza krev MeSH
- hepatitida B imunologie prevence a kontrola MeSH
- hodnotící studie jako téma MeSH
- lidé MeSH
- sérologické testy metody MeSH
- testování odbornosti laboratoří * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Hepatitis B virus uses e antigen (HBe), which is dispensable for virus infectivity, to modulate host immune responses and achieve viral persistence in human hepatocytes. The HBe precursor (p25) is directed to the endoplasmic reticulum (ER), where cleavage of the signal peptide (sp) gives rise to the first processing product, p22. P22 can be retro-translocated back to the cytosol or enter the secretory pathway and undergo a second cleavage event, resulting in secreted p17 (HBe). Here, we report that translocation of p25 to the ER is promoted by translocon-associated protein complex. We have found that p25 is not completely translocated into the ER; a fraction of p25 is phosphorylated and remains in the cytoplasm and nucleus. Within the p25 sp sequence, we have identified three cysteine residues that control the efficiency of sp cleavage and contribute to proper subcellular distribution of the precore pool.
- MeSH
- cystein metabolismus MeSH
- endoplazmatické retikulum metabolismus MeSH
- hepatitida B - antigeny e * metabolismus MeSH
- hepatitida B * metabolismus MeSH
- lidé MeSH
- membránové glykoproteiny MeSH
- proteiny - lokalizační signály genetika MeSH
- proteiny vázající vápník MeSH
- receptory cytoplazmatické a nukleární MeSH
- receptory peptidů MeSH
- virus hepatitidy B metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Imprinting broadly neutralizing antibody (bNAb) paratopes by shape complementary protein mimotopes represents a potential alternative for developing vaccine immunogens. This approach, designated as a Non-Cognate Ligand Strategy (NCLS), has recently been used for the identification of protein variants mimicking CD4 binding region epitope or membrane proximal external region (MPER) epitope of HIV-1 envelope (Env) glycoprotein. However, the potential of small binding proteins to mimic viral glycan-containing epitopes has not yet been verified. METHODS: In this work, we employed a highly complex combinatorial Myomedin scaffold library to identify variants recognizing paratopes of super candidate bNAbs, PGT121 and PGT126, specific for HIV-1 V3 loop epitopes. RESULTS: In the collection of Myomedins called MLD variants targeted to PGT121, three candidates competed with gp120 for binding to this bNAb in ELISA, thus suggesting an overlapping binding site and epitope-mimicking potential. Myomedins targeted to PGT126 designated MLB also provided variants that competed with gp120. Immunization of mice with MLB or MLD binders resulted in the production of anti-gp120 and -Env serum antibodies. Mouse hyper-immune sera elicited with MLB036, MLB041, MLB049, and MLD108 moderately neutralized 8-to-10 of 22 tested HIV-1-pseudotyped viruses of A, B, and C clades in vitro. DISCUSSION: Our data demonstrate that Myomedin-derived variants can mimic particular V3 glycan epitopes of prominent anti-HIV-1 bNAbs, ascertain the potential of particular glycans controlling neutralizing sensitivity of individual HIV-1 pseudoviruses, and represent promising prophylactic candidates for HIV-1 vaccine development.
- MeSH
- hepatitida B - antigeny povrchové krev MeSH
- hepatitida C - protilátky krev MeSH
- krevní plazma imunologie MeSH
- látky proti HIV krev MeSH
- lidé MeSH
- řízení kvality MeSH
- sérologické testy * MeSH
- testování odbornosti laboratoří statistika a číselné údaje MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- zprávy MeSH
The role of G-quadruplex (G4) RNA structures is multifaceted and controversial. Here, we have used as a model the EBV-encoded EBNA1 and the Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded LANA1 mRNAs. We have compared the G4s in these two messages in terms of nucleolin binding, nuclear mRNA retention, and mRNA translation inhibition and their effects on immune evasion. The G4s in the EBNA1 message are clustered in one repeat sequence and the G4 ligand PhenDH2 prevents all G4-associated activities. The RNA G4s in the LANA1 message take part in similar multiple mRNA functions but are spread throughout the message. The different G4 activities depend on flanking coding and non-coding sequences and, interestingly, can be separated individually. Together, the results illustrate the multifunctional, dynamic and context-dependent nature of G4 RNAs and highlight the possibility to develop ligands targeting specific RNA G4 functions. The data also suggest a common multifunctional repertoire of viral G4 RNA activities for immune evasion.
- MeSH
- G-kvadruplexy * MeSH
- intergenová DNA chemie genetika MeSH
- lidé MeSH
- regulace genové exprese MeSH
- RNA virová MeSH
- RNA chemie genetika MeSH
- transport RNA MeSH
- virus Epsteinův-Barrové - jaderné antigeny chemie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION AND AIMS: Viral hepatitis, which appears most frequently at birth or during childhood, is a disease whose transmission routes include tears, bile, sexual fluids, sweat, milk, urine, feces, and saliva. The aim of the present study was to analyze the specificity of the immunochromatographic and ELISA diagnostic tests for hepatitis B surface antigen and compare them with PCR testing. MATERIALS AND METHODS: The study sample was made up of 140 men and 60 women referred to the Urmia Medical University hospital to undergo PCR testing for HBV diagnosis. The ELISA test was performed using the Pioneer Medicine Company kit (Tehran, Iran). RESULTS: The results of the HBs-Ag rapid test and the ELISA test were compared with the PCR test. The HBs-Ag rapid test had 97% sensitivity and 91% specificity, whereas the ELISA test had 78% sensitivity and 76% specificity. DISCUSSION AND CONCLUSION: According to our results, the immunochromatographic test was accurate for diagnosing HBs-Ag in blood and the ELISA test had acceptable sensitivity and specificity, compared with PCR testing.
- MeSH
- chromatografie afinitní MeSH
- diagnostické testy rutinní MeSH
- ELISA MeSH
- hepatitida B - antigeny povrchové * MeSH
- hepatitida B * diagnóza MeSH
- lidé MeSH
- novorozenec MeSH
- polymerázová řetězová reakce MeSH
- virus hepatitidy B genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Írán MeSH
Protein aggregates and abnormal proteins are toxic and associated with neurodegenerative diseases. There are several mechanisms to help cells get rid of aggregates but little is known on how cells prevent aggregate-prone proteins from being synthesised. The EBNA1 of the Epstein-Barr virus (EBV) evades the immune system by suppressing its own mRNA translation initiation in order to minimize the production of antigenic peptides for the major histocompatibility (MHC) class I pathway. Here we show that the emerging peptide of the disordered glycine-alanine repeat (GAr) within EBNA1 dislodges the nascent polypeptide-associated complex (NAC) from the ribosome. This results in the recruitment of nucleolin to the GAr-encoding mRNA and suppression of mRNA translation initiation in cis. Suppressing NAC alpha (NACA) expression prevents nucleolin from binding to the GAr mRNA and overcomes GAr-mediated translation inhibition. Taken together, these observations suggest that EBNA1 exploits a nascent protein quality control pathway to regulate its own rate of synthesis that is based on sensing the nascent GAr peptide by NAC followed by the recruitment of nucleolin to the GAr-encoding RNA sequence.
- MeSH
- alanin MeSH
- fosfoproteiny MeSH
- glycin MeSH
- infekce virem Epsteina-Barrové * MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- peptidy genetika MeSH
- proteinové agregáty MeSH
- proteiny vázající RNA metabolismus MeSH
- virus Epsteinův-Barrové - jaderné antigeny metabolismus MeSH
- virus Epsteinův-Barrové * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
