Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14
Опубликована: Ноя. 29, 2024
Viral infection usually stimulates a variety of host cell factors to modulate the life cycle virus. PIM1, serine/threonine protein kinase widely involved in proliferation, survival, differentiation and apoptosis, was recently reported be upregulated by Zika virus (ZIKV) infection. However, how ZIKV-PIM1 interactions affect viral are not fully understood.
Язык: Английский
Cell Biochemistry and Function, Год журнала: 2024, Номер 42(8)
Опубликована: Окт. 25, 2024
ABSTRACT The endothelial semipermeable monolayers ensure tissue homeostasis, are subjected to a plethora of stimuli, and their function depends on cytoskeletal integrity remodeling. permeability those membranes can fluctuate maintain organ homeostasis. In cases severe injury, inflammation or disease, barrier hyperpermeability cause irreparable damage endothelium‐dependent issues, eventually death. Elucidation the signaling regulating structure promotes development targeted pharmacotherapies towards disorders related impaired endothelium (e.g., acute respiratory distress syndrome, sepsis). Recent reports investigate role unfolded protein response in function. Herein we review components, function; interrelations health disorder. Moreover, emphasize modulators, since they ameliorate illness leak.
Язык: Английский
Процитировано
2
FEBS Letters, Год журнала: 2023, Номер 597(23), С. 2908 - 2930
Опубликована: Ноя. 20, 2023
Several human diseases including viral infections activate the unfolded protein response (UPR) due to abnormal accumulation of unfolded/misfolded proteins. However, UPR modulation and its functional relevance in HIV‐1 infection lack comprehensive elucidation. This study reveals that activates IRE1, PERK, ATF6 signaling pathways UPR. The knockdown PERK reduces long terminal repeat (LTR)‐driven gene expression, whereas endoplasmic reticulum (ER) chaperone HSPA5 prevents proteasomal degradation p24 through activity. Interestingly, overstimulation by a chemical inducer leads anti‐HIV activity an enhanced type‐1 interferon response. Also, treatment with ER stress inhibitor replication. These findings suggest optimal activation is crucial for effective replication, as either overstimulating or inhibiting suppression.
Язык: Английский
Процитировано
4
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Март 1, 2024
Abstract AMP-activated protein kinase (AMPK) plays a central role in regulating cell energy balance. When activated, AMPK supresses energy-consuming pathways such as lipid and synthesis while increasing nutrient availability through the activation of autophagy. These downstream contribute to SARS-CoV-2 infection, which hijacks autophagy accumulates droplets viral factories support replication. Here, we assessed antiviral activity direct pan-AMPK allosteric activator MK-8722 vitro. efficiently inhibited infection Alpha Omicron variants Vero76 human bronchial epithelial Calu-3 cells at micromolar concentration. This inhibition relied on restoring autophagic flux, redirected newly synthesized proteins for degradation, reduction metabolism, affected factories. Furthermore, treatment increased type I interferon (IFN-I) response. Post-infection with was enough inhibit replication restore IFN-I Finally, did not alter SARS-CoV-2-specific CD8 + T response mounted upon Spike vaccination. Overall, by activating AMPK, acts an effective against even when applied post-exposure, paving way preclinical tests aimed inhibiting improving patients’ symptoms. Graphical abstract Highlights exerts post-exposure induces decrease cellular content promotes increase flux components restoration is compatible virus-specific responses
Язык: Английский
Процитировано
1
International Journal of Biological Macromolecules, Год журнала: 2024, Номер 268, С. 131734 - 131734
Опубликована: Апрель 21, 2024
Язык: Английский
Процитировано
1
npj Viruses, Год журнала: 2024, Номер 2(1)
Опубликована: Дек. 17, 2024
Positive-sense single-stranded RNA (+ssRNA) viruses exert a profound influence on cellular organelles and metabolic pathway by usurping host processes to promote their replication. In this review, we present portrait of selected pathways perturbed in SARS-CoV-2 infection: the effect viral translation, replication assembly morphology function ER, remodelling degradative with focus autophagic processes, alterations affecting membranes lipid metabolism. For each these highlight specific factors involved interplay microscopic tug-of-war between pro-viral anti-viral effects that ultimately tip scale toward propagation or resolution infection.
Язык: Английский
Процитировано
1
Cells, Год журнала: 2024, Номер 13(9), С. 769 - 769
Опубликована: Апрель 30, 2024
Background: SARS-Co-V2 infection can induce ER stress-associated activation of unfolded protein response (UPR) in host cells, which may contribute to the pathogenesis COVID-19. To understand complex interplay between and UPR signaling, we examined effects acute pre-existing stress on infectivity. Methods: Huh-7 cells were treated with Tunicamycin (TUN) Thapsigargin (THA) prior SARS-CoV-2pp transduction (48 h p.i.) stress. Pseudo-typed particles (SARS-CoV-2pp) entry into was measured by Bright GloTM luciferase assay. Cell viability assessed cell titer Glo® luminescent The mRNA expression evaluated RT-qPCR Western Blot. Results: TUN (5 µg/mL) THA (1 µM) efficiently inhibited without any cytotoxic effect. THA’s attenuation virus associated differential modulation ACE2 expression. Both significantly reduced stress-inducible chaperone GRP78/BiP transduced cells. In contrast, IRE1-XBP1s PERK-eIF2α-ATF4-CHOP signaling pathways downregulated treatment, but not Insulin-mediated glucose uptake phosphorylation Ser307 IRS-1 downstream p-AKT enhanced Furthermore, differentially affected lipid metabolism apoptotic pathways. Conclusions: These findings suggest that short-term induces a specific capable counteracting elements thereby depriving essential components for replication. Pharmacological manipulation might provide new therapeutic strategies alleviate SARS-CoV-2 infection.
Язык: Английский
Процитировано
0
Viruses, Год журнала: 2024, Номер 16(6), С. 859 - 859
Опубликована: Май 28, 2024
The human hepatitis delta virus (HDV) is a satellite RNA that depends on B (HBV) surface proteins (HBsAg) to assemble into infectious virions targeting the same organ (liver) as HBV. Until recently, evolutionary origin of HDV remained largely unknown. application bioinformatics whole sequence databases lead discoveries HDV-like agents (DLA) and shed light HDV’s evolution, expanding our understanding biology. DLA were identified in heterogeneous groups vertebrates invertebrates, highlighting evolution HDV, represented by eight distinct genotypes, broader more complex than previously foreseen. In this study, we focused characterization three mammalian discovered woodchuck (Marmota monax), white-tailed deer (Odocoileus virginianus), lesser dog-like bat (Peropteryx macrotis) terms replication, cell-type permissiveness, spreading pathways. We generated replication-competent constructs expressing 1.1-fold over-length antigenomic each DLA. Replication was initiated transfecting cDNAs (HuH7, HeLa, HEK293T, A549) non-human (Vero E6, CHO, PaKi, LMH) cell lines. Upon transfection replication establishment, none expressed large antigen. A division-mediated viral amplification assay demonstrated capability replicate propagate hepatic non-hepatic tissues, without requirement envelope from helper virus. Remarkably L-HDAg but not S-HDAg can artificially mediate envelopment WoDV DeDV ribonucleoproteins (RNPs) HBsAg form particles, co-transfection HuH7 cells with respective expression plasmid encoding HBV proteins. These chimeric viruses are sensitive entry inhibitors allow synchronized infections for comparative studies. Our results provide detailed molecular biology, virus–host interaction unique group animal viroid-like relation HDV.
Язык: Английский
Процитировано
0
Heliyon, Год журнала: 2024, Номер 10(13), С. e34127 - e34127
Опубликована: Июль 1, 2024
Язык: Английский
Процитировано
0
Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14
Опубликована: Ноя. 29, 2024
Viral infection usually stimulates a variety of host cell factors to modulate the life cycle virus. PIM1, serine/threonine protein kinase widely involved in proliferation, survival, differentiation and apoptosis, was recently reported be upregulated by Zika virus (ZIKV) infection. However, how ZIKV-PIM1 interactions affect viral are not fully understood.
Язык: Английский
Процитировано
0