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1.
Rev Med Virol ; 33(4): e2452, 2023 07.
Article in English | MEDLINE | ID: mdl-37119022

ABSTRACT

Fibroblast growth factors (FGFs) are a family of proteins that play a crucial role in the development and maintenance of various tissues in the body. There are three function-al groups of FGFs: canonical FGFs (cFGFs), intracellularly retained FGFs, and metabolic (also called endocrine) FGFs. cFGFs are secreted and act in an autocrine/paracrine fashion to regulate differentiation during foetal development, as well as tissue repair in adults. Recent studies have also begun to unravel the role of cFGFs during viral infections, suggesting that FGF-2 and other canonical FGFs may have an important virus-specific role, also by the regulation of the immune response. Because dysregulation in the FGF pathways is pivotal in cancer development, FGFs are the target of many anticancer drugs. These drugs may be repurposed to treat viral infection, since dysregulation of FGF signalling has been implicated in the pathogenesis of viral infections, such as hepatitis C. Overall, the role of cFGFs during viral infection is an underrepresented area of current research. This review focuses on overviewing the effects of canonical FGFs during infection by different viruses. Many studies highlight that the effects of FGFs during viral infection may be complex and context-dependent. While there is evidence to suggest that FGFs may have a beneficial impact on the immune response and tissue repair during viral infection, further studies are needed to fully understand the mechanisms underlying these effects and to determine in what cases FGFs could be targeted as a therapeutic approach for viral infection.


Subject(s)
Antineoplastic Agents , Neoplasms , Virus Diseases , Humans , Fibroblast Growth Factors/metabolism , Neoplasms/metabolism
2.
Phytochem Rev ; : 1-79, 2023 Mar 12.
Article in English | MEDLINE | ID: mdl-37359711

ABSTRACT

Viral infections have always been the main global health challenge, as several potentially lethal viruses, including the hepatitis virus, herpes virus, and influenza virus, have affected human health for decades. Unfortunately, most licensed antiviral drugs are characterized by many adverse reactions and, in the long-term therapy, also develop viral resistance; for these reasons, researchers have focused their attention on investigating potential antiviral molecules from plants. Natural resources indeed offer a variety of specialized therapeutic metabolites that have been demonstrated to inhibit viral entry into the host cells and replication through the regulation of viral absorption, cell receptor binding, and competition for the activation of intracellular signaling pathways. Many active phytochemicals, including flavonoids, lignans, terpenoids, coumarins, saponins, alkaloids, etc., have been identified as potential candidates for preventing and treating viral infections. Using a systematic approach, this review summarises the knowledge obtained to date on the in vivo antiviral activity of specialized metabolites extracted from plant matrices by focusing on their mechanism of action.

3.
J Virol ; 95(23): e0135821, 2021 11 09.
Article in English | MEDLINE | ID: mdl-34549986

ABSTRACT

Gene editing may be used to excise the human immunodeficiency virus type 1 (HIV-1) provirus from the host cell genome, possibly eradicating the infection. Here, using cells acutely or latently infected by HIV-1 and treated with long terminal repeat (LTR)-targeting CRISPR/Cas9, we show that the excised HIV-1 provirus persists for a few weeks and may rearrange in circular molecules. Although circular proviral DNA is naturally formed during HIV-1 replication, we observed that gene editing might increase proviral DNA circles with restored LTRs. These extrachromosomal elements were recovered and probed for residual activity through their transfection in uninfected cells. We discovered that they can be transcriptionally active in the presence of Tat and Rev. Although confirming that gene editing is a powerful tool to eradicate HIV-1 infection, this work highlights that, to achieve this goal, the LTRs must be cleaved in several pieces to avoid residual activity and minimize the risk of reintegration in the context of genomic instability, possibly caused by the off-target activity of Cas9. IMPORTANCE The excision of HIV-1 provirus from the host cell genome has proven feasible in vitro and, to some extent, in vivo. Among the different approaches, CRISPR/Cas9 is the most promising tool for gene editing. The present study underlines the remarkable effectiveness of CRISPR/Cas9 in removing the HIV-1 provirus from infected cells and investigates the fate of the excised HIV-1 genome. This study demonstrates that the free provirus may persist in the cell after editing and in appropriate circumstances may reactivate. As an episome, it might be transcriptionally active, especially in the presence of Tat and Rev. The persistence of the HIV-1 episome was strongly decreased by gene editing with multiple targets. Although gene editing has the potential to eradicate HIV-1 infection, this work highlights a potential issue that warrants further investigation.


Subject(s)
CRISPR-Cas Systems , DNA, Circular , HIV-1/genetics , Proviruses/genetics , Terminal Repeat Sequences , CRISPR-Associated Protein 9 , Gene Editing , Gene Expression Regulation, Viral , Genetic Therapy , HEK293 Cells , HIV Infections/virology , Humans , RNA, Guide, Kinetoplastida/genetics
4.
New Microbiol ; 44(4): 191-204, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34942015

ABSTRACT

Life implies adaptation. This is one of the fundamental principles that has permitted most living species to survive through ages in an ever-changing environment. Spontaneously occurring events have shaped also virus populations and their fitness. Thanks to their plasticity, viruses have thrived in extremely dissimilar conditions. Unsurprisingly, SARS-CoV-2, the etiological agent of COVID-19, is no exception. Thanks to an unprecedented rate of molecular tracing and sequence scrutiny, the virus was followed in all its changes and shown to evolve in such a way as to possibly determine subsequent waves of infection after the first global and massive outbreak. This review illustrates the major modifications occurred to the virus since its discovery. We describe the potential advantages that these changes conveyed as regards SARS-CoV-2 transmissibility, resistance to host innate and adaptive barriers and molecular diagnosis.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Spike Glycoprotein, Coronavirus
5.
Int J Mol Sci ; 22(6)2021 Mar 23.
Article in English | MEDLINE | ID: mdl-33806766

ABSTRACT

Cutaneous melanoma is often resistant to therapy due to its high plasticity, as well as its ability to metabolise chemotherapeutic drugs. Sphingolipid signalling plays a pivotal role in its progression and metastasis. One of the ways melanoma alters sphingolipid rheostat is via over-expression of lysosomal acid ceramidase (AC), which catalyses the hydrolysis of pro-apoptotic long-chain ceramides into sphingosine and fatty acid. In this report, we examine the role of acid ceramidase in maintaining cellular homeostasis through the regulation of autophagy and mitochondrial activity in melanoma cell lines. We show that under baseline conditions, wild-type melanoma cells had 3-fold higher levels of the autophagy marker, microtubule-associated proteins 1A/1B light chain 3B (LC3 II), compared to AC-null cells. This difference was further magnified after cell starvation. Moreover, we noticed autophagy impairment in A375 AC-null cells, possibly due to local accumulation of non-metabolized ceramides. Nonetheless, we observed that AC-null cells exhibited a significant increase in mitochondrial membrane potential compared to control cells. Consistent with this observation, we found that, after total starvation, ~30% of AC-null cells undergo apoptosis compared to ~6% of wild-type cells. As expected, AC transfection restored viability in A375 AC-null cells. Together, these findings suggest that AC-null melanoma cells change and adapt their metabolism to survive in the absence of AC, although in a way that does not allow them to cope with the stress of nutrient deprivation.


Subject(s)
Acid Ceramidase/genetics , Autophagy/genetics , Melanoma/genetics , Melanoma/metabolism , Mitochondria/genetics , Acid Ceramidase/metabolism , Apoptosis/genetics , Cell Line, Tumor , Fluorescent Antibody Technique , Gene Expression , Humans , Melanoma/pathology , Membrane Potential, Mitochondrial , Microphthalmia-Associated Transcription Factor/genetics , Mitochondria/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics
6.
Int J Mol Sci ; 20(14)2019 Jul 12.
Article in English | MEDLINE | ID: mdl-31336922

ABSTRACT

Melanoma is a malignant tumor deriving from neoplastic transformation of melanocytes. The incidence of melanoma has increased dramatically over the last 50 years. It accounts for most cases of skin cancer deaths. Early diagnosis leads to remission in 90% of cases of melanoma; conversely, for melanoma at more advanced stages, prognosis becomes more unfavorable also because dvanced melanoma is often resistant to pharmacological and radiological therapies due to genetic plasticity, presence of cancer stem cells that regenerate the tumor, and efficient elimination of drugs. This review illustrates the role of autophagy in tumor progression and resistance to therapy, focusing on molecular targets for future drugs.


Subject(s)
Autophagy , Cell Transformation, Neoplastic/metabolism , Ceramides/metabolism , Disease Susceptibility , Melanoma/metabolism , Signal Transduction , Sphingolipids/metabolism , Acid Ceramidase/metabolism , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Autophagy/drug effects , Biomarkers, Tumor , Disease Progression , Drug Resistance, Neoplasm , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Lipid Metabolism , Melanoma/etiology , Melanoma/pathology , Melanoma/therapy , Signal Transduction/drug effects
7.
New Microbiol ; 41(2): 95-105, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29498740

ABSTRACT

Varicella-zoster virus (VZV) is the etiologic agent of varicella (chicken pox), a childhood exanthematic disease that develops as a result of primary infection, and zoster (shingles), caused by reactivation of the virus persisting in a latent form in the dorsal sensory ganglia. Although varicella is generally a mild self-limiting illness, in immunocompromised subjects and adults it can have a serious clinical course that can lead to permanent damage of the central nervous system. In these and in most zoster cases, treatment with anti-herpetic drugs and/or immunotherapy is necessary. Because it is highly contagious, varicella is one of the most common exanthematic diseases. It is preventable by vaccination with an attenuated vaccine administered around the first year of age, and with a boost vaccination in school age. This article briefly describes the natural history and pathophysiology of VZV infection and its current epidemiology and provides an overview of current and future vaccine options to protect against varicella and/or zoster.


Subject(s)
Chickenpox Vaccine/immunology , Chickenpox/prevention & control , Herpes Zoster/prevention & control , Chickenpox/virology , Herpes Zoster/virology , Humans , Vaccination , Vaccines, Attenuated
8.
Cytotherapy ; 18(2): 205-18, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26794713

ABSTRACT

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) modulate the immune response and represent a potential treatment for inflammatory and autoimmune diseases. We hypothesized that this feature could be potentiated by co-administering anti-inflammatory cytokines. In this article, we asked whether engineering of Wharton Jelly-derived human MSCs (WJ-hMSCs) to express an anti-inflammatory cytokine increases cell immunomodulatory properties without altering their native features. METHODS: We used Epstein-Barr virus-derived interleukin-10 (vIL-10), which shares some immunosuppressive properties with human IL-10 but lacks immunostimulatory activity. Engineering was accomplished by transducing WJ-hMSCs with a self-inactivating feline immunodeficiency virus-derived vector co-expressing vIL-10 and herpes simplex virus type-1 thymidine kinase (TK). TK was added to allow future tracking of WJ-hMSC in vivo by positron electron tomography (PET). RESULTS: The results show that (i) expression of TK and/or vIL-10 does not change WJ-hMSC phenotypic and functional properties; (ii) vIL-10 is secreted, biologically active and enhances the immunosuppressing functions of WJ-hMSCs; (iii) v-IL10 and TK can be produced simultaneously by the same cells and do not interfere with each other. DISCUSSION: WJ-hMSCs engineered to secrete vIL-10 could be a powerful tool for adoptive cell therapy of immune-mediated diseases, and therefore, additional studies are warranted to confirm their efficacy in suitable animal disease models.


Subject(s)
Interleukin-10/metabolism , Thymidine Kinase/metabolism , Wharton Jelly/cytology , Animals , Cell Line , HEK293 Cells , Herpesvirus 4, Human/genetics , Humans , Immunodeficiency Virus, Feline/genetics , Immunosuppression Therapy , Immunosuppressive Agents , Immunotherapy, Adoptive/methods , Interleukin-10/genetics , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/immunology , Thymidine Kinase/genetics , Wharton Jelly/metabolism
9.
Methods ; 61(1): 30-8, 2013 May 15.
Article in English | MEDLINE | ID: mdl-23583887

ABSTRACT

Intracellular cytokine staining is a flow cytometric technique consisting of culturing stimulated cytokine-producing cells in the presence of a protein secretion inhibitor, followed by fixation, permeabilization and staining of intracellular cytokines and cell markers (surface or cytoplasmic) with fluorescent antibodies. Up to 18 different colors can be detected by modern flow cytometers, making it the only immunological technique allowing simultaneous determination of antigen-specific T cell function and phenotype. In addition, cell proliferation and viability can be also measured. For this reason, it is probably the most popular method to measure antigenicity during vaccine trials and in the study of infectious diseases, along with ELISPOT. In this review, we will summarize its features, provide the protocol used by most laboratories and review its most recent applications.


Subject(s)
Cytokines/analysis , Cytosol/chemistry , Flow Cytometry/methods , T-Lymphocytes/immunology , Antigens, Bacterial/pharmacology , Cell Proliferation/drug effects , Cell Survival/drug effects , Cytokines/biosynthesis , Flow Cytometry/instrumentation , Fluorescent Antibody Technique , Humans , Immunophenotyping , Lipopolysaccharides/pharmacology , Lymphocyte Activation/drug effects , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , Tissue Fixation
10.
J Virol ; 86(12): 6563-74, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22491465

ABSTRACT

Genital herpes is caused by herpes simplex virus 1 (HSV-1) and HSV-2, and its incidence is constantly increasing in the human population. Regardless of the clinical manifestation, HSV-1 and HSV-2 infections are highly transmissible to sexual partners and enhance susceptibility to other sexually transmitted infections. An effective vaccine is not yet available. Here, HSV-1 glycoprotein B (gB1) was delivered by a feline immunodeficiency virus (FIV) vector and tested against HSV-1 and HSV-2 vaginal challenges in C57BL/6 mice. The gB1 vaccine elicited cross-neutralizing antibodies and cell-mediated responses that protected 100 and 75% animals from HSV-1- and HSV-2-associated severe disease, respectively. Two of the eight fully protected vaccinees underwent subclinical HSV-2 infection, as demonstrated by deep immunosuppression and other analyses. Finally, vaccination prevented death in 83% of the animals challenged with a HSV-2 dose that killed 78 and 100% naive and mock-vaccinated controls, respectively. Since this FIV vector can accommodate two or more HSV immunogens, this vaccine has ample potential for improvement and may become a candidate for the development of a truly effective vaccine against genital herpes.


Subject(s)
Cross Protection , Herpes Genitalis/immunology , Herpes Simplex Virus Vaccines/immunology , Herpesvirus 1, Human/physiology , Herpesvirus 2, Human/physiology , Viral Envelope Proteins/immunology , Animals , Female , Genetic Vectors/genetics , Genetic Vectors/metabolism , Herpes Genitalis/prevention & control , Herpes Genitalis/virology , Herpes Simplex Virus Vaccines/administration & dosage , Herpes Simplex Virus Vaccines/genetics , Herpesvirus 1, Human/genetics , Herpesvirus 1, Human/immunology , Herpesvirus 2, Human/genetics , Herpesvirus 2, Human/immunology , Humans , Immunity, Cellular , Immunodeficiency Virus, Feline/genetics , Immunodeficiency Virus, Feline/metabolism , Mice , Mice, Inbred C57BL , Vaccination , Viral Envelope Proteins/administration & dosage , Viral Envelope Proteins/genetics
11.
Infect Agent Cancer ; 18(1): 45, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37496079

ABSTRACT

Parasite infection is one of the many environmental factors that can significantly contribute to carcinogenesis and is already known to be associated with a variety of malignancies in both human and veterinary medicine. However, the actual number of cancerogenic parasites and their relationship to tumor development is far from being fully understood, especially in veterinary medicine. Thus, the aim of this review is to investigate parasite-related cancers in domestic and wild animals and their burden in veterinary oncology. Spontaneous neoplasia with ascertained or putative parasite etiology in domestic and wild animals will be reviewed, and the multifarious mechanisms of protozoan and metazoan cancer induction will be discussed.

12.
Infect Agent Cancer ; 18(1): 40, 2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37386451

ABSTRACT

Currently, it is estimated that 15% of human neoplasms globally are caused by infectious agents, with new evidence emerging continuously. Multiple agents have been implicated in various forms of neoplasia, with viruses as the most frequent. In recent years, investigation on viral mechanisms underlying tumoral transformation in cancer development and progression are in the spotlight, both in human and veterinary oncology. Oncogenic viruses in veterinary medicine are of primary importance not only as original pathogens of pets, but also in the view of pets as models of human malignancies. Hence, this work will provide an overview of the main oncogenic viruses of companion animals, with brief notes of comparative medicine.

13.
Antiviral Res ; 216: 105664, 2023 08.
Article in English | MEDLINE | ID: mdl-37414288

ABSTRACT

Recent evidence suggests that lipids play a crucial role in viral infections beyond their traditional functions of supplying envelope and energy, and creating protected niches for viral replication. In the case of Zika virus (ZIKV), it alters host lipids by enhancing lipogenesis and suppressing ß-oxidation to generate viral factories at the endoplasmic reticulum (ER) interface. This discovery prompted us to hypothesize that interference with lipogenesis could serve as a dual antiviral and anti-inflammatory strategy to combat the replication of positive sense single-stranded RNA (ssRNA+) viruses. To test this hypothesis, we examined the impact of inhibiting N-Acylethanolamine acid amidase (NAAA) on ZIKV-infected human Neural Stem Cells. NAAA is responsible for the hydrolysis of palmitoylethanolamide (PEA) in lysosomes and endolysosomes. Inhibition of NAAA results in PEA accumulation, which activates peroxisome proliferator-activated receptor-α (PPAR-α), directing ß-oxidation and preventing inflammation. Our findings indicate that inhibiting NAAA through gene-editing or drugs moderately reduces ZIKV replication by approximately one log10 in Human Neural Stem Cells, while also releasing immature virions that have lost their infectivity. This inhibition impairs furin-mediated prM cleavage, ultimately blocking ZIKV maturation. In summary, our study highlights NAAA as a host target for ZIKV infection.


Subject(s)
Zika Virus Infection , Zika Virus , Humans , Amidohydrolases/antagonists & inhibitors , Amidohydrolases/metabolism , Anti-Inflammatory Agents/pharmacology , Inflammation/drug therapy , Zika Virus Infection/drug therapy
14.
BMC Public Health ; 12: 472, 2012 Jun 21.
Article in English | MEDLINE | ID: mdl-22897910

ABSTRACT

BACKGROUND: Tuberculosis (TB) surveillance systems have some pitfalls outside of a National Tuberculosis Program and lack of efficient surveillance hampers accurate epidemiological quantification of TB burden.In the present study we assessed the quality of surveillance at the University Hospital in Pisa (UHP), Italy, and TB incidence rates over a ten year period (1999-2008). METHODS: Assessment of underreporting was done by record-linkage from two sources: databases of TB diagnoses performed in the UHP and the Italian Infectious Disease Surveillance (IIDS) system. Two different databases were examined: a) TB diagnoses reported in the Hospital Discharge Records (HDR) from three Units of UHP (Respiratory Pathophysiology, Pulmonology and Infectious Diseases Units) (TB database A); b) TB diagnoses reported in HDR of all Units of UHP plus TB positive cases obtained by the Laboratory Register (LR) of UHP (TB database B). For the TB database A, the accuracy of TB diagnosis in HDR was assessed by direct examination of the Clinical Record Forms of the cases. For the TB database B, clinical and population data were described, as well as the trend of incidence and underreporting over 10 yrs. RESULTS: In the first study 293 patients were found: 80 patients (27%) with a confirmed TB diagnosis were underreported, 39 of them were microbiologically confirmed. Underreporting was related to age (Reported vs Non Reported, mean age: 49.27 ± 20 vs 55 ± 19, p < 0.005 ), diagnosis (smear positive vs negative cases 18.7 vs 81.2%, p = 0.001), microbiological confirmation (49% vs 51%, p < 0.05), X-ray findings (cavitary vs non-cavitary cases: 12.5 vs 87.5%, p = 0.001) but not to nationality.In the second study, 666 patients were found. Mean underreporting rate was 69.4% and decreased over time (68% in 1999, 48% in 2008). Newly diagnosed TB cases were also found to decrease in number whereas immigration rate increased. Underreporting was related to nationality (Immigrants vs Italians: 18% vs 68%, p < 0.001), diagnosis (microbiological confirmation: 25% vs 75%, p < 0.01), kind of hospital regimen (hospitalized patients vs Day Hospital: 70% vs 16%, p < 0.001), and position of TB code in the HDR (TB code in first position vs in the following position: 39,5% vs 45% p < 0.001). CONCLUSIONS: TB is underreported in Pisa, particularly in older patients and those without microbiological confirmation. The TB code in first position of HDR seems fairly accurate in confirming TB diagnosis.


Subject(s)
Disease Notification/standards , Population Surveillance , Tuberculosis, Pulmonary/epidemiology , Hospitals, University , Humans , Italy/epidemiology , Medical Record Linkage
15.
Viruses ; 14(5)2022 05 06.
Article in English | MEDLINE | ID: mdl-35632719

ABSTRACT

Since its discovery as a milk factor, mouse mammary tumor virus (MMTV) has been shown to cause mammary carcinoma and lymphoma in mice. MMTV infection depends upon a viral superantigen (sag)-induced immune response and exploits the immune system to establish infection in mammary epithelial cells when they actively divide. Simultaneously, it avoids immune responses, causing tumors through insertional mutagenesis and clonal expansion. Early studies identified antigens and sequences belonging to a virus homologous to MMTV in human samples. Several pieces of evidence fulfill a criterion for a possible causal role for the MMTV-like virus in human breast cancer (BC), though the controversy about whether this virus was linked to BC has raged for over 40 years in the literature. In this review, the most important issues related to MMTV, from its discovery to the present days, are retraced to fully explore such a controversial issue. Furthermore, the hypothesis of an MMTV-like virus raised the question of a potential zoonotic mouse-man transmission. Several studies investigate the role of an MMTV-like virus in companion animals, suggesting their possible role as mediators. Finally, the possibility of an MMTV-like virus as a cause of human BC opens a new era for prevention and therapy.


Subject(s)
Breast Neoplasms , Retroviridae Infections , Animals , Female , Humans , Mammary Tumor Virus, Mouse/genetics , Mice
16.
Stem Cell Reports ; 17(7): 1683-1698, 2022 07 12.
Article in English | MEDLINE | ID: mdl-35714598

ABSTRACT

Congenital alterations in the levels of the transcription factor Forkhead box g1 (FOXG1) coding gene trigger "FOXG1 syndrome," a spectrum that recapitulates birth defects found in the "congenital Zika syndrome," such as microcephaly and other neurodevelopmental conditions. Here, we report that Zika virus (ZIKV) infection alters FOXG1 nuclear localization and causes its downregulation, thus impairing expression of genes involved in cell replication and apoptosis in several cell models, including human neural progenitor cells. Growth factors, such as EGF and FGF2, and Thr271 residue located in FOXG1 AKT domain, take part in the nuclear displacement and apoptosis protection, respectively. Finally, by progressive deletion of FOXG1 sequence, we identify the C-terminus and the residues 428-481 as critical domains. Collectively, our data suggest a causal mechanism by which ZIKV affects FOXG1, its target genes, cell cycle progression, and survival of human neural progenitors, thus contributing to microcephaly.


Subject(s)
Microcephaly , Neural Stem Cells , Zika Virus Infection , Zika Virus , Down-Regulation , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Humans , Microcephaly/genetics , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neural Stem Cells/metabolism , Zika Virus/physiology , Zika Virus Infection/genetics
17.
Infect Agent Cancer ; 17(1): 35, 2022 Jun 23.
Article in English | MEDLINE | ID: mdl-35739602

ABSTRACT

The mouse mammary tumour virus (MMTV) is implicated in the aetiology of murine mammary carcinomas and a variant of it, the type B leukemogenic virus, can cause murine thymic lymphomas. Interestingly, a MMTV-like virus is suspected to be involved in human breast cancer and feline mammary carcinomas. However, to date, no cases of MMTV-like sequence amplifications have been described in lymphoid neoplasms in veterinary literature. The aim of this study was to investigate the presence of env nucleotide sequences and protein 14 (p14) of a MMTV-like virus in fifty-three feline lymphoma samples. Our results show that MMTV-like sequences were detected in 5/53 tumours (9.4%): three gastrointestinal lymphomas (one B-type diffuse large, one B-type small non-cleaved, and one T-type diffuse mixed lymphoma); and two nasal lymphomas (one B-type diffuse small cleaved lymphoma and one B-type diffuse mixed lymphoma). P14 expression was detected in the cytoplasm, and rarely in nuclei, exclusively of neoplastic cells from PCR-positive tumours. The correlation between the presence of the MMTV-env like sequences (MMTVels) and p14 antigen was statistically significant in nasal lymphomas. All cats with MMTVels-positive lymphoma had a history of contact with the outdoor environment and/or catteries, and two deceased subjects shared their environment with cats that also died of lymphoma. In conclusion, this study succeeds in demonstrating the presence of MMTVels and p14 in feline lymphomas. The characterization of the immunophenotype of MMTVels-positive lymphomas could contribute to the understanding of a possible role of a MMTV-like virus in feline tumour aetiology. The significant association between the presence of the viral sequences in lymphoid tumours and their nasal localization, together with the data collected through supplementary anamnesis, should be further analysed in order to understand the epidemiology of the virus.

18.
J Virol Methods ; 299: 114327, 2022 01.
Article in English | MEDLINE | ID: mdl-34644588

ABSTRACT

Mollicutes (Mycoplasma and Acholeplasma) are parasitic bacteria that adhere to cellular surfaces, naturally resistant to many antibiotics and extremely small. They are often found as contaminants in cultured cells, where they go unnoticed. They may be present in viral stocks because they are present in supernatants of cells where cultured viruses are released. The best way to keep laboratories free of Mycoplasma is to discard infected cultures, but, as judged by the very common finding of Mycoplasma-contaminated cultures in many laboratories, this is not done as often as it should be. A possible reason is that most procedures recommended take as long as performing a simple experiment and many laboratories delay testing to save money and time. Indeed, many methods exist to detect Mycoplasma infection of cell lines, but they take at least a couple of hours of hands-on work, if not more. Here we describe a procedure to screen viral stocks and tissue cultures for Mycoplasma presence. It relies on isolation of Mycoplasma on ordinary horse blood agar directly from exhausted tissue culture supernatants and does not require experienced personnel or expensive equipment. It only requires minutes of hands-on work, and, for this, it may be useful for weekly screening of cultures. It yields semiquantitative results in roughly 5 days, which is the time that usually passes between one subculture passage of cells in vitro to another. Because of its simplicity, it may be useful for detecting Mycoplasma in viral stocks and for frequent screening of cultures in research laboratories.


Subject(s)
Mycoplasma Infections , Mycoplasma hyorhinis , Mycoplasma , Cell Culture Techniques , Cells, Cultured , Humans , Mycoplasma Infections/diagnosis
19.
Viruses ; 14(5)2022 05 17.
Article in English | MEDLINE | ID: mdl-35632821

ABSTRACT

Lipids play a crucial role in the entry and egress of viruses, regardless of whether they are naked or enveloped. Recent evidence shows that lipid involvement in viral infection goes much further. During replication, many viruses rearrange internal lipid membranes to create niches where they replicate and assemble. Because of the close connection between lipids and inflammation, the derangement of lipid metabolism also results in the production of inflammatory stimuli. Due to its pivotal function in the viral life cycle, lipid metabolism has become an area of intense research to understand how viruses seize lipids and to design antiviral drugs targeting lipid pathways. Palmitoylethanolamide (PEA) is a lipid-derived peroxisome proliferator-activated receptor-α (PPAR-α) agonist that also counteracts SARS-CoV-2 entry and its replication. Our work highlights for the first time the antiviral potency of PEA against SARS-CoV-2, exerting its activity by two different mechanisms. First, its binding to the SARS-CoV-2 S protein causes a drop in viral infection of ~70%. We show that this activity is specific for SARS-CoV-2, as it does not prevent infection by VSV or HSV-2, other enveloped viruses that use different glycoproteins and entry receptors to mediate their entry. Second, we show that in infected Huh-7 cells, treatment with PEA dismantles lipid droplets, preventing the usage of these vesicular bodies by SARS-CoV-2 as a source of energy and protection against innate cellular defenses. This is not surprising since PEA activates PPAR-α, a transcription factor that, once activated, generates a cascade of events that leads to the disruption of fatty acid droplets, thereby bringing about lipid droplet degradation through ß-oxidation. In conclusion, the present work demonstrates a novel mechanism of action for PEA as a direct and indirect antiviral agent against SARS-CoV-2. This evidence reinforces the notion that treatment with this compound might significantly impact the course of COVID-19. Indeed, considering that the protective effects of PEA in COVID-19 are the current objectives of two clinical trials (NCT04619706 and NCT04568876) and given the relative lack of toxicity of PEA in humans, further preclinical and clinical tests will be needed to fully consider PEA as a promising adjuvant therapy in the current COVID-19 pandemic or against emerging RNA viruses that share the same route of replication as coronaviruses.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Amides , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Ethanolamines , Humans , Palmitic Acids/pharmacology , Pandemics , Pisum sativum , Peroxisome Proliferator-Activated Receptors , Spike Glycoprotein, Coronavirus
20.
Antiviral Res ; 206: 105398, 2022 10.
Article in English | MEDLINE | ID: mdl-35985406

ABSTRACT

A marked reorganization of internal membranes occurs in the cytoplasm of cells infected by single stranded positive-sense RNA viruses. Most cell compartments change their asset to provide lipids for membrane rearrangement into replication organelles, where to concentrate viral proteins and enzymes while hiding from pathogen pattern recognition molecules. Because the endoplasmic reticulum is a central hub for lipid metabolism, when viruses hijack the organelle to form their replication organelles, a cascade of events change the intracellular environment. This results in a marked increase in lipid consumption, both by lipolysis and lipophagy of lipid droplets. In addition, lipids are used to produce energy for viral replication. At the same time, inflammation is started by signalling lipids, where lysosomal processing plays a relevant role. This review is aimed at providing an overview on what takes place after human class IV viruses have released their genome into the host cell and the consequences on lipid metabolism, including lysosomes.


Subject(s)
Positive-Strand RNA Viruses , RNA Viruses , Endoplasmic Reticulum/metabolism , Humans , Lipids , Lysosomes/metabolism , RNA, Viral/metabolism , Virus Replication
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