scholarly journals Function of Membrane Rafts in Viral Lifecycles and Host Cellular Response

2011 ◽  
Vol 2011 ◽  
pp. 1-23 ◽  
Author(s):  
Tadanobu Takahashi ◽  
Takashi Suzuki
Keyword(s):  
Cellular Response ◽  
Viral Infections ◽  
Early Stage ◽  
Rna Virus ◽  
Membrane Rafts ◽  
Dna Virus ◽  
Cellular Processes ◽  
Viral Virulence ◽  
Cellular Signal ◽  
Induced Signal

Membrane rafts are small (10–200 nm) sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts play an important role in viral infection cycles and viral virulence. Viruses are divided into four main classes, enveloped DNA virus, enveloped RNA virus, nonenveloped DNA virus, and nonenveloped RNA virus. General virus infection cycle is also classified into two sections, the early stage (entry process) and the late stage (assembly, budding, and release processes of virus particles). In the viral cycle, membrane rafts act as a scaffold of many cellular signal transductions, which are associated with symptoms caused by viral infections. In this paper, we describe the functions of membrane rafts in viral lifecycles and host cellular response according to each virus classification, each stage of the virus lifecycle, and each virus-induced signal transduction.

scholarly journals THE EFFECT OF INDUCED CHRONIC VIRAL INFECTIONS ON THE IMMUNOLOGIC DISEASES OF NEW ZEALAND MICE

1970 ◽  
Vol 132 (1) ◽  
pp. 89-109 ◽  
Author(s):  
Giorgio Tonietti ◽  
Michael B. A. Oldstone ◽  
Frank J. Dixon
Keyword(s):  
New Zealand ◽  
Autoimmune Hemolytic Anemia ◽  
Viral Infections ◽  
Rna Virus ◽  
Red Cell ◽  
Chronic Infections ◽  
Dna Virus ◽  
Chronic Viral Infections ◽  
Immunologic Diseases ◽  
Capillary Walls

Chronic infections induced at birth with either LCM, an RNA virus, or polyoma, a DNA virus, in NZB, NZW, and NZB x W mice enhance ANA formation, aggravate the immune complex glomerulonephritis, and increase the associated mortality. The ANA titer was increased without apparent change in specificity of the antibodies involved in all three types of mice. Glomerulonephritis, while more severe in infected mice, was of the same type as occurred spontaneously and was characterized by a granular to lumpy accumulation of host IgG and C3 in the mesangia and along the capillary walls of the glomeruli. Of the LCM infected mice of all three types over 50% had died of glomerulonephritis by 6 months and over 85% by 9 months. Of the polyoma infected mice of all three types approximately 20% had died of glomerulonephritis by 6 months and over 40% by 9 months. Of the uninfected controls of all three types less than 10% had died by 6 months and less than 20% at 9 months except for the NZB x W females which had a 67% mortality at 9 months as a result of their spontaneous glomerulonephritis. The two viral infections had significant effect on the incidence of anti-red cell antibodies or the severity of autoimmune hemolytic anemia in any of the three NZ mice.

scholarly journals Quantitative conversion of biomass in giant DNA virus infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mikael Kördel ◽  
Martin Svenda ◽  
Hemanth K. N. Reddy ◽  
Emelie Fogelqvist ◽  
Komang G. Y. Arsana ◽  
...  
Keyword(s):  
Cellular Response ◽  
Chemical Engineering ◽  
Viral Infections ◽  
Morphological Changes ◽  
Burst Size ◽  
Gravimetric Analysis ◽  
Dna Virus ◽  
X Ray ◽  
Large Size ◽  
Viral Factory

AbstractBioconversion of organic materials is the foundation of many applications in chemical engineering, microbiology and biochemistry. Herein, we introduce a new methodology to quantitatively determine conversion of biomass in viral infections while simultaneously imaging morphological changes of the host cell. As proof of concept, the viral replication of an unidentified giant DNA virus and the cellular response of an amoebal host are studied using soft X-ray microscopy, titration dilution measurements and thermal gravimetric analysis. We find that virions produced inside the cell are visible from 18 h post infection and their numbers increase gradually to a burst size of 280–660 virions. Due to the large size of the virion and its strong X-ray absorption contrast, we estimate that the burst size corresponds to a conversion of 6–12% of carbonaceous biomass from amoebal host to virus. The occurrence of virion production correlates with the appearance of a possible viral factory and morphological changes in the phagosomes and contractile vacuole complex of the amoeba, whereas the nucleus and nucleolus appear unaffected throughout most of the replication cycle.

scholarly journals Fludarabine Inhibits Infection of Zika Virus, SFTS Phlebovirus, and Enterovirus A71

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 774
Author(s):  
Chengfeng Gao ◽  
Chunxia Wen ◽  
Zhifeng Li ◽  
Shuhan Lin ◽  
Shu Gao ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Zika Virus ◽  
Therapeutic Agent ◽  
Viral Infections ◽  
Rna Virus ◽  
Emerging Viruses ◽  
Enterovirus A71 ◽  
Ic50 Values ◽  
High Doses ◽  
Severe Fever

Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC50 values below 1 μM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.

scholarly journals Redox-Modulating Agents in the Treatment of Viral Infections

2020 ◽  
Vol 21 (11) ◽  
pp. 4084 ◽  
Author(s):  
Paola Checconi ◽  
Marta De Angelis ◽  
Maria Elena Marcocci ◽  
Alessandra Fraternale ◽  
Mauro Magnani ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Redox State ◽  
Viral Infections ◽  
Rna Virus ◽  
Influenza Virus Infection ◽  
Redox Balance ◽  
Physiological Conditions ◽  
Cell Functions ◽  
Enzymatic Systems ◽  
Strong Inflammatory Response

Viruses use cell machinery to replicate their genome and produce viral proteins. For this reason, several intracellular factors, including the redox state, might directly or indirectly affect the progression and outcome of viral infection. In physiological conditions, the redox balance between oxidant and antioxidant species is maintained by enzymatic and non-enzymatic systems, and it finely regulates several cell functions. Different viruses break this equilibrium and induce an oxidative stress that in turn facilitates specific steps of the virus lifecycle and activates an inflammatory response. In this context, many studies highlighted the importance of redox-sensitive pathways as novel cell-based targets for therapies aimed at blocking both viral replication and virus-induced inflammation. In the review, we discuss the most recent findings in this field. In particular, we describe the effects of natural or synthetic redox-modulating molecules in inhibiting DNA or RNA virus replication as well as inflammatory pathways. The importance of the antioxidant transcription factor Nrf2 is also discussed. Most of the data reported here are on influenza virus infection. We believe that this approach could be usefully applied to fight other acute respiratory viral infections characterized by a strong inflammatory response, like COVID-19.

scholarly journals An ultra-sensitive, ultra-fast whole blood monocyte CD169 assay for COVID-19 screening

2020 ◽  
Author(s):  
Moïse Michel ◽  
Fabrice Malergue ◽  
Inès Ait Belkacem ◽  
Pénélope Bourgoin ◽  
Pierre-Emmanuel Morange ◽  
...  
Keyword(s):  
Whole Blood ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Early Stage ◽  
Polymorphonuclear Neutrophil ◽  
Blood Monocyte ◽  
Rt Pcr ◽  
Neutrophil Cd64 ◽  
Asymptomatic Patients ◽  
Hla Dr

AbstractCoVID-19 is an unprecedented epidemic, globally challenging health systems, societies, and economy. Its diagnosis relies on molecular methods, with drawbacks revealed by current use as mass screening. Monocyte CD169 upregulation has been reported as a marker of viral infections, we evaluated a flow cytometry three-color rapid assay of whole blood monocyte CD169 for CoVID-19 screening.Outpatients (n=177) with confirmed CoVID-19 infection, comprising 80 early-stage (≤14 days after symptom onset), 71 late-stage (≥15 days), and 26 asymptomatic patients received whole blood CD169 testing in parallel with SARS-CoV-2 RT-PCR. Upregulation of monocyte CD169 without polymorphonuclear neutrophil CD64 changes was the primary endpoint. Sensitivity was 98% and 100% in early-stage and asymptomatic patients respectively, specificity was 50% and 84%. Rapid whole blood monocyte CD169 evaluation was highly sensitive when compared with RT-PCR, especially in early-stage, asymptomatic patients whose RT-PCR tests were not yet positive.Diagnostic accuracy, easy finger prick sampling and minimal time-to-result (15-30 minutes) rank whole blood monocyte CD169 upregulation as a potential screening and diagnostic support for CoVID-19. Secondary endpoints were neutrophil CD64 upregulation as a marker of bacterial infections and monocyte HLA-DR downregulation as a surrogate of immune fitness, both assisting with adequate and rapid management of non-CoVID cases.

scholarly journals Analysis of Porcine RIG-I Like Receptors Revealed the Positive Regulation of RIG-I and MDA5 by LGP2

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuangjie Li ◽  
Jie Yang ◽  
Yuanyuan Zhu ◽  
Hui Wang ◽  
Xingyu Ji ◽  
...  
Keyword(s):  
Cell Activation ◽  
Viral Infections ◽  
Rna Virus ◽  
Gene Knockout ◽  
Constitutive Activity ◽  
Virus Infections ◽  
Positive Regulation ◽  
Dsrna Binding ◽  
Livestock Animal ◽  
Signaling Activity

The RLRs play critical roles in sensing and fighting viral infections especially RNA virus infections. Despite the extensive studies on RLRs in humans and mice, there is a lack of systemic investigation of livestock animal RLRs. In this study, we characterized the porcine RLR members RIG-I, MDA5 and LGP2. Compared with their human counterparts, porcine RIG-I and MDA5 exhibited similar signaling activity to distinct dsRNA and viruses, via similar and cooperative recognitions. Porcine LGP2, without signaling activity, was found to positively regulate porcine RIG-I and MDA5 in transfected porcine alveolar macrophages (PAMs), gene knockout PAMs and PK-15 cells. Mechanistically, LGP2 interacts with RIG-I and MDA5 upon cell activation, and promotes the binding of dsRNA ligand by MDA5 as well as RIG-I. Accordingly, porcine LGP2 exerted broad antiviral functions. Intriguingly, we found that porcine LGP2 mutants with defects in ATPase and/or dsRNA binding present constitutive activity which are likely through RIG-I and MDA5. Our work provided significant insights into porcine innate immunity, species specificity and immune biology.

scholarly journals Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation

2021 ◽  
Vol 11 ◽  
Author(s):  
Kingsley Gideon Kumashie ◽  
Marcin Cebula ◽  
Claudia Hagedorn ◽  
Florian Kreppel ◽  
Marina C. Pils ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Viral Infections ◽  
Cell Formation ◽  
T Cell Response ◽  
Cellular Processes ◽  
Metabolic Functions ◽  
Cpg Oligonucleotide ◽  
Novel Approach

Chronic hepatotropic viral infections are characterized by exhausted CD8+ T cells in the presence of cognate antigen in the liver. The impairment of T cell response limits the control of chronic hepatotropic viruses. Immune-modulatory strategies are attractive options to re-invigorate exhausted T cells. However, in hepatotropic viral infections, the knowledge about immune-modulatory effects on the in-situ regulation of exhausted intrahepatic CD8+ T cells is limited. In this study, we elucidated the functional heterogeneity in the pool of exhausted CD8+ T cells in the liver of mice expressing the model antigen Ova in a fraction of hepatocytes. We found a subpopulation of intrahepatic CXCR5+ Ova-specific CD8+ T cells, which are profoundly cytotoxic, exhibiting efficient metabolic functions as well as improved memory recall and self-maintenance. The intrahepatic Ova-specific CXCR5+ CD8+ T cells are possibly tissue resident cells, which may rely largely on OXPHOS and glycolysis to fuel their cellular processes. Importantly, host conditioning with CpG oligonucleotide reinvigorates and promotes exhausted T cell expansion, facilitating complete antigen eradication. The CpG oligonucleotide-mediated reinvigoration may support resident memory T cell formation and the maintenance of CXCR5+ Ova-specific CD8+ T cells in the liver. These findings suggest that CpG oligodinucleotide may preferentially target CXCR5+ CD8+ T cells for expansion to facilitate the revival of exhausted T cells. Thus, therapeutic strategies aiming to expand CXCR5+ CD8+ T cells might provide a novel approach against chronic liver infection.

Mechanisms of Action of Ribavirin in Antiviral Therapies

2001 ◽  
Vol 12 (5) ◽  
pp. 261-272 ◽  
Author(s):  
Robert C Tam ◽  
Johnson YN Lau ◽  
Zhi Hong
Keyword(s):  
Hepatitis C ◽  
Viral Infections ◽  
Rna Virus ◽  
Lassa Fever ◽  
Biological Properties ◽  
Interferon Α ◽  
Hepatitis C Infection ◽  
Antiviral Activities ◽  
Syncytial Virus

Although ribavirin was originally synthesized over 30 years ago and has been used to treat viral infections as monotherapy (respiratory syncytial virus and Lassa fever virus) or with interferon-α (IFN-α) as combination therapy (hepatitis C virus), the precise mechanism of its therapeutic activities remains controversial. In this review we focus on two main biological properties of ribavirin: its indirect and direct antiviral activities (with particular emphasis on its efficacy against chronic hepatitis C infection). Each property could individually or collectively account for its clinical efficacy against viral infections. First, with emphasis on the evidence for indirect activities of ribavirin, we will review the clinical observations that suggest that the immunomodulatory properties of ribavirin can in part account for its antiviral activities in vivo. We will then describe the mode of ribavirin's direct antiviral activities. These direct activities can be ascribed to several possible mechanisms, including the recently described activity as an RNA mutagen, a property that may be important in driving a rapidly mutating RNA virus over the threshold to ‘error catastrophe′.

Mechanosensitive myosin II but not cofilin primarily contributes to cyclic cell stretch-induced selective disassembly of actin stress fibers

2021 ◽  
Author(s):  
Wenjing Huang ◽  
Tsubasa S. Matsui ◽  
Takumi Saito ◽  
Masahiro Kuragano ◽  
Masayuki Takahashi ◽  
...  
Keyword(s):  
Cellular Response ◽  
Early Stage ◽  
Myosin Ii ◽  
Cyclic Stretch ◽  
Stress Fibers ◽  
Lim Kinase ◽  
Lim Kinase 1 ◽  
Chronic Activation ◽  
Selective Disassembly ◽  
Actin Stress Fibers

Cells adapt to applied cyclic stretch (CS) to circumvent chronic activation of proinflammatory signaling. Currently, the molecular mechanism of the selective disassembly of actin stress fibers (SFs) in the stretch direction, which occurs at the early stage of the cellular response to CS, remains controversial. Here we suggest that the mechanosensitive behavior of myosin II, a major cross-linker of SFs, primarily contributes to the directional disassembly of the actomyosin complex SFs in bovine vascular smooth muscle cells and human U2OS osteosarcoma cells. First, we identified that CS with a shortening phase that exceeds in speed the inherent contractile rate of individual SFs leads to the disassembly. To understand the biological basis, we investigated the effect of expressing myosin regulatory light chain mutants and found that SFs with less actomyosin activities disassemble more promptly upon CS. We consequently created a minimal mathematical model that recapitulates the salient features of the direction-selective and threshold-triggered disassembly of SFs to show that disassembly or, more specifically, unbundling of the actomyosin bundle SFs is enhanced with sufficiently fast cell shortening. We further demonstrated that similar disassembly of SFs is inducible in the presence of an active LIM-kinase-1 mutant that deactivates cofilin, suggesting that cofilin is dispensable as opposed to a previously proposed mechanism.

Effect of Radiotherapy After Breast-Conserving Treatment in Women With Breast Cancer and Germline BRCA1/2 Mutations

2000 ◽  
Vol 18 (19) ◽  
pp. 3360-3369 ◽  
Author(s):  
Lori J. Pierce ◽  
Myla Strawderman ◽  
Steven A. Narod ◽  
Ivo Oliviotto ◽  
Andrea Eisen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cellular Response ◽  
Breast Tissue ◽  
Early Stage ◽  
Subcutaneous Tissue ◽  
Conditional Logistic Regression ◽  
Radiation Therapy Oncology Group ◽  
Laboratory Data ◽  
Tumor Control ◽  
European Organization

PURPOSE: Recent laboratory data suggest a role for BRCA1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from BRCA1/2 mutation carriers. Thus the goals of this study were to compare rates of radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA1/2 mutations treated with breast-conserving therapy (BCT) using RT with rates observed in sporadic disease. PATIENTS AND METHODS: Seventy-one women with a BRCA1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used to compare matched cohorts for rates of complications and recurrence. RESULTS: Tumors from women in the genetic cohort were associated with high histologic (P = .0004) and nuclear (P = .009) grade and negative estrogen (P = .0001) and progesterone (P = .002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scoring, there were no significant differences in acute or chronic morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial overall survival, relapse-free survival, and rates of tumor control in the treated breast for the patients in the genetic cohort were 86%, 78%, and 98%, respectively, compared with 91%, 80%, and 96%, respectively, for the sporadic cohort (P = not significant). CONCLUSION: There was no evidence of increased radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA1/2 carriers and controls at 5 years. Although additional follow-up is needed, these data may help in discussing treatment options in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers of a germline BRCA1/2 mutation.

Sign in / Sign up

Export Citation Format

Share Document