We explored how a simple retrovirus, Mason-Pfizer monkey virus (M-PMV) to facilitate its replication process, utilizes DHX15, a cellular RNA helicase, typically engaged in RNA processing. Through advanced genetic engineering techniques, we showed that M-PMV recruits DHX15 by mimicking cellular mechanisms, relocating it from the nucleus to the cytoplasm to aid in viral assembly. This interaction is essential for the correct packaging of the viral genome and critical for its infectivity. Our findings offer unique insights into the mechanisms of viral manipulation of host cellular processes, highlighting a sophisticated strategy that viruses employ to leverage cellular machinery for their replication. This study adds valuable knowledge to the understanding of viral-host interactions but also suggests a common evolutionary history between cellular processes and viral mechanisms. This finding opens a unique perspective on the export mechanism of intron-retaining mRNAs in the packaging of viral genetic information and potentially develop ways to stop it.
- MeSH
- buněčné jádro metabolismus virologie MeSH
- DEAD-box RNA-helikasy metabolismus genetika MeSH
- genom virový MeSH
- HEK293 buňky MeSH
- lidé MeSH
- Masonův-Pfizerův opičí virus * genetika metabolismus fyziologie MeSH
- replikace viru genetika fyziologie MeSH
- RNA virová * metabolismus genetika MeSH
- RNA-helikasy metabolismus genetika MeSH
- sestavení viru * genetika fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Rinovírusy paria medzi najčastejšie sa vyskytujúcich pôvodcov respiračných ochorení rozličného charakteru od „bežného prechladnutia“ až po klinicky závažné bronchiolitídy či pneumónie u dojčiat a batoliat. Problematika vzťahu rinovírusových infekcií u predisponovaných jedincov, najmä detí v dojčenskom a batolivom veku s následným rizikom rozvoja bronchiálnej astmy bola za posledné dve dekády predmetom mnohých klinických štúdií. Početné zložité a komplexné interakcie rinovírusov s epiteliálnymi bunkami a jednotlivými zložkami imunitného systému ešte nie sú dostatočne a podrobne ozrejmené. Niektoré špecifické patomechanizmy a ich následky, ktoré indukuje vstup a replikácia rinovírusov v bunkách respiračného epitelu, sú už známe. Z klinického pohľadu je vynakladaná čoraz väčšia snaha čo najexaktnejšie identifikovať vonkajšie a vnútorné faktory, ktoré v kontexte opakovaných rinovírusových infekcií predisponujú nositeľa k rekurentným vírusmi indukovaným bronchospazmom a rizikom nadobudnutia astmy. V prvej časti prehľadového príspevku sú rinovírusy analyzované z virologického a epidemiologického hľadiska s prihliadnutím na determinujúce vonkajšie faktory rinovírusových infekcií.
Rhinoviruses are one of the most common causative agents of respiratory diseases from common cold to clinically severe bronchiolitis and pneumonia in infants and toddlers. The relationship of rhinovirus infections in predisposed individuals, especially infants and toddlers, with subsequent risk of bronchial asthma development has been the aim of many clinical studies over the last two decades. The multiple complex and involved interactions of rhinoviruses with epithelial cells and various elements of the immune system have not yet been sufficiently and extensively understood. Some specific pathomechanisms and their consequences induced by the entry and replication of rhinoviruses in respiratory epithelial cells are already known. From a clinical point of view, increasing effort is being devoted to identifying extrinsic and intrinsic factors that, in the context of recurrent rhinovirus infections, predispose the host to recurrent virus-induced bronchospasm and risk of asthma development. In this first part of the review, rhinoviruses are analysed from a virological and epidemiological point of view, with consideration of the determining external factors of rhinovirus infections.
- MeSH
- bronchiální astma * epidemiologie virologie MeSH
- dítě MeSH
- lidé MeSH
- náchylnost k nemoci * mikrobiologie MeSH
- replikace viru fyziologie MeSH
- Rhinovirus * fyziologie klasifikace MeSH
- virulence MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
In mammals, protein arginine methyltransferase 5, PRMT5, is the main type II enzyme responsible for the majority of symmetric dimethylarginine formation in polypeptides. Recent study reported that PRMT5 restricts Hepatitis B virus (HBV) replication through epigenetic repression of HBV DNA transcription and interference with encapsidation of pregenomic RNA. Here we demonstrate that PRMT5 interacts with the HBV core (HBc) protein and dimethylates arginine residues within the arginine-rich domain (ARD) of the carboxyl-terminus. ARD consists of four arginine rich subdomains, ARDI, ARDII, ARDIII and ARDIV. Mutation analysis of ARDs revealed that arginine methylation of HBc required the wild-type status of both ARDI and ARDII. Mass spectrometry analysis of HBc identified multiple potential ubiquitination, methylation and phosphorylation sites, out of which lysine K7 and arginines R150 (within ARDI) and R156 (outside ARDs) were shown to be modified by ubiquitination and methylation, respectively. The HBc symmetric dimethylation appeared to be linked to serine phosphorylation and nuclear import of HBc protein. Conversely, the monomethylated HBc retained in the cytoplasm. Thus, overexpression of PRMT5 led to increased nuclear accumulation of HBc, and vice versa, down-regulation of PRMT5 resulted in reduced levels of HBc in nuclei of transfected cells. In summary, we identified PRMT5 as a potent controller of HBc cell trafficking and function and described two novel types of HBc post-translational modifications (PTMs), arginine methylation and ubiquitination.
- MeSH
- fosforylace MeSH
- hmotnostní spektrometrie MeSH
- lidé MeSH
- metylace MeSH
- proteinarginin-N-methyltransferasy metabolismus fyziologie MeSH
- replikace viru fyziologie MeSH
- subcelulární frakce metabolismus MeSH
- ubikvitinace MeSH
- virus hepatitidy B enzymologie fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- imunopatogeneze,
- MeSH
- Cytomegalovirus imunologie patogenita MeSH
- Herpesviridae imunologie klasifikace patogenita MeSH
- imunitní únik fyziologie imunologie MeSH
- lidé MeSH
- lidský herpesvirus 1 imunologie patogenita MeSH
- přirozená imunita MeSH
- replikace viru fyziologie imunologie MeSH
- virové nemoci imunologie patofyziologie MeSH
- virus Epsteinův-Barrové imunologie patogenita MeSH
- virus spalniček imunologie patogenita MeSH
- viry hepatitidy imunologie patogenita MeSH
- viry * imunologie klasifikace patogenita MeSH
- zánět * etiologie imunologie patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
This review focuses on recent advances in HIV research and therapy that seek to eradicate persistent HIV in patients on suppressive therapy. RECENT FINDINGS: The source of persistent HIV in patients on suppressive therapy is debated. Recent studies of treatment intensification have produced varied results: no reduction in low-level plasma viremia indicating the source of persistent viremia is long-lived HIV-infected cells that release HIV when activated and increase in episomal HIV DNA indicating active replication persists in some infected individuals on suppressive therapy. In addition, clonal HIV sequences found in plasma from patients on long-term suppressive therapy are rarely found in CD4+ memory T cells. These results indicate that persistent viremia may arise from several different sources. Recent studies emphasize the complexity of HIV latency. Current strategies for HIV eradication focus on compounds that activate viral transcription in memory CD4+ T cells by many routes, including inhibiting histone deacetylation and activating nuclear factor kappa B. Several compounds and combinations of these compounds appear to induce the expression of integrated HIV in different latency models. SUMMARY: The eradication of HIV requires the elimination of persistent HIV during suppressive therapy. Recent studies have focused on the source of persistent viremia, mechanisms of intracellular HIV latency, and reactivation of latent HIV. It remains to be seen whether alternative treatment strategies may be required to eradicate HIV.
- MeSH
- aktivace viru MeSH
- CD4-pozitivní T-lymfocyty virologie MeSH
- financování organizované MeSH
- HIV infekce farmakoterapie imunologie virologie MeSH
- HIV séropozitivita farmakoterapie virologie MeSH
- HIV fyziologie genetika účinky léků MeSH
- latence viru fyziologie účinky léků MeSH
- látky proti HIV farmakologie terapeutické užití MeSH
- lidé MeSH
- replikace viru fyziologie účinky léků MeSH
- RNA virová krev účinky léků MeSH
- T-lymfocyty - podskupiny virologie MeSH
- viremie farmakoterapie virologie MeSH
- vysoce aktivní antiretrovirová terapie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
We undertook a comparative study of the susceptibility of different tick cell lines to infection with the European subtype of tick-borne encephalitis virus (TBEV), prototype strain Neudoerfl. The growth of TBEV was investigated in lines derived from vector Ixodes ricinus L. ticks (IRE/CTVM18, 19, and 20), as well as non-vector ticks, namely Ixodes scapularis Say (IDE2), Boophilus microplus Canestrini (BME/CTVM2), Hyalomma anatolicum anatolicum Koch (HAE/CTVM9), Rhipicephalus appendiculatus Neumann (RA-257) and recently established and herein described lines from the argasid tick Ornithodoros moubata Murray (OME/CTVM21 and 22). All the tick cell lines tested were susceptible to infection by TBEV and the virus caused productive infection without any cytopathic effect. However, there was a clear difference between the TBEV growth in vector and non-vector cell lines, since I. ricinus cell lines produced 100-1000-fold higher virus yield than the non-vector cell lines. The lowest virus production was observed in O. moubata and R. appendiculatus cell lines.
- MeSH
- arachnida jako vektory cytologie virologie MeSH
- buněčné linie MeSH
- časové faktory MeSH
- financování organizované MeSH
- klíšťata cytologie virologie MeSH
- kultivace virů MeSH
- protilátky virové metabolismus MeSH
- replikace viru fyziologie MeSH
- viry klíšťové encefalitidy růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
Retroviral proteases are translated as a part of Gag-related polyproteins, and are released and activated during particle release. Mason-Pfizer monkey virus (M-PMV) Gag polyproteins assemble into immature capsids within the cytoplasm of the host cells; however, their processing occurs only after transport to the plasma membrane and subsequent release. Thus, the activity of M-PMV protease is expected to be highly regulated during the replication cycle. It has been proposed that reversible oxidation of protease cysteine residues might be responsible for such regulation. We show that cysteine residues in M-PMV protease can form an intramolecular S-S bridge. The disulfide bridge shifts the monomer/dimer equilibrium in favor of the dimer, and increases the proteolytic activity significantly. To investigate the role of this disulfide bridge in virus maturation and replication, we engineered an M-PMV clone in which both protease cysteine residues were replaced by alanine (M-PMV(PRC7A/C106A)). Surprisingly, the cysteine residues were dispensable for Gag polyprotein processing within the virus, indicating that even low levels of protease activity are sufficient for polyprotein processing during maturation. However, the long-term infectivity of M-PMV(PRC7A/C106A) was noticeably compromised. These results show clearly that the proposed redox mechanism does not rely solely on the formation of the stabilizing S-S bridge in the protease. Thus, in addition to the protease disulfide bridge, reversible oxidation of cysteine and/or methionine residues in other domains of the Gag polyprotein or in related cellular proteins must be involved in the regulation of maturation.
- MeSH
- bromkyan metabolismus MeSH
- Cercopithecus aethiops MeSH
- COS buňky MeSH
- cystein metabolismus MeSH
- dimerizace MeSH
- disulfidy metabolismus MeSH
- endopeptidasy chemie metabolismus ultrastruktura MeSH
- financování organizované MeSH
- fluorescenční spektrometrie MeSH
- genové produkty gag metabolismus MeSH
- kinetika MeSH
- Masonův-Pfizerův opičí virus enzymologie fyziologie MeSH
- molekulární sekvence - údaje MeSH
- molekulová hmotnost MeSH
- mutantní proteiny chemie metabolismus MeSH
- nukleární magnetická rezonance biomolekulární MeSH
- posttranslační úpravy proteinů MeSH
- replikace viru fyziologie MeSH
- retrovirové infekce MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- stabilita enzymů MeSH
- termodynamika MeSH
- virion fyziologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
