RESUMO
SARS-CoV-2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN-I) response in children and adolescents with LC symptoms (LC; n = 28). This was compared with age-matched SARS-CoV-2 recovered participants without LC symptoms (MC; n = 28) and healthy controls (HC; n = 18). We measured the mRNA expression of IFN-I (IFN-α/ß/ε/ω), IFN-I receptor (IFNAR1/2), and ISGs (ISG15, ISG56, MxA, IFI27, BST2, LY6E, OAS1, OAS2, OAS3, and MDA5) in PBMCs collected 3-6 months after COVID-19. LC adolescents (12-17 years) had higher transcript levels of IFN-ß, IFN-ε, and IFN-ω than HC, whereas LC children (6-11 years) had lower levels than HC. In adolescents, increased levels of IFN-α, IFN-ß, and IFN-ω mRNAs were found in the LC group compared with MC, while lower levels were observed in LC children than MC. Adolescents with neurological symptoms had higher IFN-α/ß mRNA levels than MC. LC and MC participants showed decreased expression of ISGs and IFNAR1, but increased expression of IFNAR2, than HC. Our results show age-related changes in the expression of transcripts involved in the IFN-I signaling pathway in children and adolescents with LC.
Assuntos
COVID-19 , Interferon Tipo I , SARS-CoV-2 , Transdução de Sinais , Humanos , Criança , Adolescente , Interferon Tipo I/metabolismo , Interferon Tipo I/imunologia , Interferon Tipo I/genética , Masculino , COVID-19/imunologia , Feminino , Transdução de Sinais/imunologia , SARS-CoV-2/imunologia , Imunidade Inata , Fatores Etários , Síndrome de COVID-19 Pós-Aguda , RNA Mensageiro/genéticaRESUMO
Knowledge of Human Polyomavirus (HPyV) infection in the anal area and its association with sexually transmitted infections such as Human Papillomavirus (HPV) and Human Immunodeficiency Virus (HIV) remains limited. Therefore, anal specimens from 150 individuals of both sexes were analyzed for screening purposes. HPV DNA was found in 50.7% of cases, with a predominance of high-risk (HR) genotypes. HPyV DNA was found in 39.3% of samples, with Merkel Cell Polyomavirus (MCPyV) being the most common, with a higher viral load than JCPyV and BKPyV. In addition, MCPyV viral load increased in people living with HIV (PLWH) with HPV infection (p < 0.0001).
Assuntos
Coinfecção , Infecções por HIV , Poliomavírus das Células de Merkel , Infecções por Papillomavirus , Infecções por Polyomavirus , Carga Viral , Humanos , Masculino , Feminino , Infecções por HIV/virologia , Infecções por HIV/complicações , Infecções por Papillomavirus/virologia , Adulto , Pessoa de Meia-Idade , Coinfecção/virologia , Coinfecção/epidemiologia , Poliomavírus das Células de Merkel/genética , Poliomavírus das Células de Merkel/isolamento & purificação , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/epidemiologia , DNA Viral/genética , Genótipo , Canal Anal/virologia , Canal Anal/patologia , Idoso , Adulto Jovem , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Papillomaviridae/classificação , Infecções Tumorais por Vírus/virologia , Infecções Tumorais por Vírus/epidemiologia , PrevalênciaRESUMO
Ultraviolet-C (UVC) has been used to cause virus inactivation. The virucidal activity of three UV light lamps [UVC high frequencies (HF), UVC+B LED and UVC+A LED] was evaluated against the enveloped feline coronavirus (FCoVII), a surrogate model of SARS-CoV-2, the enveloped vesicular stomatitis virus (VSV), and the naked encephalomyocarditis virus (EMCV). Virucidal assays were performed at different time points of UV-light exposure (i.e., 5, 30 minutes and 1, 6, and 8 hours), placing each virus 180 cm below the perpendicular irradiation of the lamp and 1 and 2 meters from the perpendicular axis. We found that the UVC HF lamp had virucidal effects (≥96.8% of virus inactivation) against FCoVII, VSV and EMCV after 5 minutes of irradiation at each distance analyzed. Moreover, the UVC+B LED lamp had the highest inhibitory effects on FCoVII and VSV infectivity (≥99% of virus inactivation) when these viruses were settled below the perpendicular axis of the lamp for 5 minutes. Conversely, the UVC+A LED lamp was the least effective, achieving ≥85.9% inactivation of enveloped RNA viruses after 8 hours of UV exposure. Overall, UV light lamps, and in particular UVC HF and UVC+B LED ones, had a rapid and strong virucidal activity against distinct RNA viruses, including coronaviruses.
Assuntos
COVID-19 , Vírus , Humanos , Raios Ultravioleta , SARS-CoV-2 , DesinfecçãoRESUMO
Merkel cell polyomavirus (MCPyV) has been detected in respiratory specimens including those from Cystic Fibrosis (CF) patients, raising questions about its immunological and clinical relevance in the respiratory tract. MCPyV might promote an inappropriate antiviral response contributing to a chronic inflammatory response and resulting in detrimental effects in CF. Respiratory samples (n = 1138) were randomly collected from respiratory tract of CF patients (n = 539) during July 2018-October 2019. MCPyV-DNA detection was performed by real time PCR and positive samples were characterized by sequencing of the NCCR genomic region. The transcript levels of Toll-like receptor 9 (TLR9) and type I interferon (IFN-I) genes (IFNα, IFNß and IFNε) were examined by real-time RT-PCR assays. MCPyV-DNA was detected in 268 out of 1138 respiratory specimens (23.5%) without any difference in the prevalence of MCPyV-DNA according to age, gender or bacteriological status of CF individuals. Thirteen out of 137 CF patients remained positive for MCPyV-DNA over the time (a median follow-up period of 8.8 months). Detection of MCPyV-DNA in respiratory specimens was not associated with the occurrence of exacerbation events. Both MCPyV positive adolescents (11-24 years) and adults (≥25 years) had lower mRNA levels of TLR9, IFNß, IFNε and IFNα than the negative patients of the same age group, while MCPyV positive children produced increased levels of TLR9 and IFN-I genes (p < 0.05 for TLR9, IFNß, IFNε) with respect to the negative ones. There were significant differences in TLR9 levels (p < 0.01), but not in those of IFNs, between MCPyV-DNA positive and negative patients with S. aureus, P. aeruginosa or both. Overall, these results indicate that MCPyV-DNA is frequently detected in the respiratory samples of CF patients and might influence the expression levels of IFN-related genes in an age dependent manner. The concomitant detection of MCPyV together with S. aureus and/or P. aeruginosa correlated with alterations in TLR9 levels suggesting that virus-bacteria coinfections might contribute to affect antiviral immunity in CF patients.
Assuntos
Fibrose Cística , Poliomavírus das Células de Merkel , Infecções por Polyomavirus , Adolescente , Adulto , Antivirais , Criança , Fibrose Cística/complicações , DNA Viral/análise , DNA Viral/genética , Humanos , Poliomavírus das Células de Merkel/genética , Infecções por Polyomavirus/epidemiologia , Prevalência , Pseudomonas aeruginosa/genética , Staphylococcus aureus/genética , Receptor Toll-Like 9/genéticaRESUMO
In recent decades, increases in temperature and tropical rainfall have facilitated the spread of mosquito species into temperate zones. Mosquitoes are vectors for many viruses, including West Nile virus (WNV) and dengue virus (DENV), and pose a serious threat to public health. This review covers most of the current knowledge on the mosquito species associated with the transmission of WNV and DENV and their geographical distribution and discusses the main vertebrate hosts involved in the cycles of WNV or DENV. It also describes virological and pathogenic aspects of WNV or DENV infection, including emerging concepts linking WNV and DENV to the reproductive system. Furthermore, it provides an epidemiological analysis of the human cases of WNV and DENV reported in Europe, from 1 January 2018 to 31 December 2023, with a particular focus on Italy. The first autochthonous cases of DENV infection, with the most likely vector being Aedes albopictus, have been observed in several European countries in recent years, with a high incidence in Italy in 2023. The lack of treatments and effective vaccines is a serious challenge. Currently, the primary strategy to prevent the spread of WNV and DENV infections in humans remains to limit the spread of mosquitoes.
RESUMO
The SARS-CoV-2 protease (3CLpro) is one of the key targets for the development of efficacious drugs for COVID-19 treatment due to its essential role in the life cycle of the virus and exhibits high conservation among coronaviruses. Recent studies have shown that flavonoids, which are small natural molecules, have antiviral activity against coronaviruses (CoVs), including SARS-CoV-2. In this study, we identified the docking sites and binding affinity of several natural compounds, similar to flavonoids, and investigated their inhibitory activity towards 3CLpro enzymatic activity. The selected compounds were then tested in vitro for their cytotoxicity, for antiviral activity against SARS-CoV-2, and the replication of other coronaviruses in different cell lines. Our results showed that Baicalein (100 µg/mL) exerted strong 3CLpro activity inhibition (>90%), whereas Hispidulin and Morin displayed partial inhibition. Moreover, Baicalein, up to 25 µg/mL, hindered >50% of SARS-CoV-2 replication in Vero E6 cultures. Lastly, Baicalein displayed antiviral activity against alphacoronavirus (Feline-CoV) and betacoronavirus (Bovine-CoV and HCoV-OC43) in the cell lines. Our study confirmed the antiviral activity of Baicalein against SARS-CoV-2 and demonstrated clear evidence of its pan-coronaviral activity.
RESUMO
Contradictory results have been reported regarding interferon (IFN) lambda (λ1-3) and IFN gamma (γ) production in COVID-19 patients. To gain insight into the roles played by these IFNs in SARS-CoV-2 infection, IFNλ1-3 and IFNγ mRNA expression was evaluated in peripheral blood mononuclear cells (PBMCs) (n = 32) and in cells of paired bronchoalveolar lavages (BALs) (n = 12). Lower IFNλ1-3 values (p < 0.001 for IFNλ1 and 3 and p = 0.013 for IFNλ2) in the PBMCs of severely ill patients were found compared to healthy donors (n = 15). Reduced levels of IFNγ were also detected in patients' PBMCs (p < 0.01) and BALs (p = 0.041) compared to healthy donors. The presence of secondary bacterial infections was associated with decreased IFNλ amounts in PBMCs (p = 0.001, p = 0.015 and p = 0.003, respectively) but increased concentrations of IFNλ3 (p = 0.022) in BALs. Patients with alterations in C-reactive protein, lactate dehydrogenase and D-dimer levels had decreased IFNλ1 and 3 (p = 0.003 and p < 0.001) and increased IFNγ (p = 0.08) in PBMCs. Analyzing Toll-like receptors (TLRs) involved in IFN production, we found that TLR3 was highly expressed (p = 0.033) in patients with bacterial superinfections, while TLR7 and 8 (p = 0.029 and p = 0.049) were reduced in BALs of deceased patients. Overall, severe COVID-19 might be characterized by dysregulation in IFNγ, IFNλ and TLR3, 7 and 8 production.
RESUMO
Type III interferons (IFN-III), also known as IFN-Lambda, have a pivotal role during SARS-CoV-2 infection. IFN-Lambda response among individuals is heterogeneous and its association with COVID-19 symptoms severity needs to be further clarified. We analyzed the genotype frequencies of IFNL4 single nucleotide polymorphism (SNP) rs11322783 in patients with COVID-19 (n = 128), in comparison with a validated data set of European healthy controls (n = 14152). The IFNL4 SNP was also analyzed according to the haematological and clinical parameters of patients with COVID-19. The distributions of IFNL4 genotypes among SARS-CoV-2 positive patients [TT/TT 41.4% (n = 53), TT/ΔG 47.7% (n = 61) and ΔG/ΔG 10.9% (n = 14)] and healthy controls were comparable. Different levels of white blood cells (p = 0.036) and neutrophils (p = 0.042) were found in the IFNL4 different genotypes in patients with COVID-19; the ΔG/ΔG genotype was more represented in the groups with low white blood cells and neutrophils. There were no differences in major inflammation parameters (C-reactive protein, D-dimer, Albumin, and Lactate-dehydrogenase (LDH)] and survival rate according to the IFNL4 genotypes. In conclusion, although patients with COVID-19 did not exhibit a different distribution of the IFNL4 SNP, the ΔG/ΔG genotype was associated with a lower count of immune cell populations. These findings need to be confirmed in larger groups of patients with COVID-19 and the role of IFNL4 SNP needs to be also investigated in other respiratory viral infections.