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1.
Immunology ; 167(3): 287-302, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35971810

RESUMEN

The COVID-19 pandemic has represented an unprecedented challenge for the humanity, and scientists around the world provided a huge effort to elucidate critical aspects in the fight against the pathogen, useful in designing public health strategies, vaccines and therapeutic approaches. One of the first pieces of evidence characterizing the SARS-CoV-2 infection has been its breadth of clinical presentation, ranging from asymptomatic to severe/deadly disease, and the indication of the key role played by the immune response in influencing disease severity. This review is aimed at summarizing what the SARS-CoV-2 infection taught us about the immune response, highlighting its features of a double-edged sword mediating both protective and pathogenic processes. We will discuss the protective role of soluble and cellular innate immunity and the detrimental power of a hyper-inflammation-shaped immune response, resulting in tissue injury and immunothrombotic events. We will review the importance of B- and T-cell immunity in reducing the clinical severity and their ability to cross-recognize viral variants.


Asunto(s)
COVID-19 , Humanos , Inmunidad , Inflamación , Pandemias , SARS-CoV-2
2.
Clin Infect Dis ; 71(16): 2272-2275, 2020 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-32407466

RESUMEN

Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.


Asunto(s)
COVID-19/inmunología , Inflamación/sangre , Células Asesinas Naturales/inmunología , Perforina/inmunología , Linfocitos T Citotóxicos/inmunología , Anciano , COVID-19/sangre , Citocinas/inmunología , Femenino , Humanos , Inflamación/complicaciones , Inflamación/inmunología , Unidades de Cuidados Intensivos/estadística & datos numéricos , Italia , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , SARS-CoV-2
3.
J Antimicrob Chemother ; 75(10): 2977-2980, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32607555

RESUMEN

BACKGROUND: Remdesivir is a prodrug of the nucleoside analogue GS-441524 and is under evaluation for treatment of SARS-CoV-2-infected patients. OBJECTIVES: To evaluate the pharmacokinetics of remdesivir and GS-441524 in plasma, bronchoalveolar aspirate (BAS) and CSF in two critically ill COVID-19 patients. METHODS: Remdesivir was administered at 200 mg loading dose on the first day followed by 12 days of 100 mg in two critically ill patients. Blood samples were collected immediately after (C0) and at 1 (C1) and 24 h (C24) after intravenous administration on day 3 until day 9. BAS samples were collected on Days 4, 7 and 9 from both patients while one CSF on Day 7 was obtained in one patient. Remdesivir and GS-441524 concentrations were measured in these samples using a validated UHPLC-MS/MS method. RESULTS: We observed higher concentrations of remdesivir at C0 (6- to 7-fold higher than EC50 from in vitro studies) and a notable decay at C1. GS-441524 plasma concentrations reached a peak at C1 and persisted until the next administration. Higher concentrations of GS-441524 were observed in the patient with mild renal dysfunction. Mean BAS/plasma concentration ratios of GS-441524 were 2.3% and 6.4% in Patient 1 and Patient 2, respectively. The CSF concentration found in Patient 2 was 25.7% with respect to plasma. GS-441524 levels in lung and CNS suggest compartmental differences in drug exposure. CONCLUSIONS: We report the first pharmacokinetic evaluation of remdesivir and GS-441524 in recovered COVID-19 patients. Further study of the pharmacokinetic profile of remdesivir, GS-441524 and the intracellular triphosphate form are required.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Adenosina Trifosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/farmacocinética , Betacoronavirus , Infecciones por Coronavirus/metabolismo , Enfermedad Crítica/terapia , Neumonía Viral/metabolismo , Adenosina Monofosfato/farmacocinética , Adenosina Monofosfato/uso terapéutico , Adenosina Trifosfato/farmacocinética , Adenosina Trifosfato/uso terapéutico , Anciano , Alanina/farmacocinética , Alanina/uso terapéutico , Antivirales/uso terapéutico , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Femenino , Humanos , Masculino , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , SARS-CoV-2
4.
J Transl Med ; 18(1): 233, 2020 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-32522207

RESUMEN

BACKGROUND: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. METHODS: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. RESULTS: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. CONCLUSIONS: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets.


Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/virología , Redes Reguladoras de Genes , Interacciones Huésped-Patógeno , Modelos Biológicos , Neumonía Viral/genética , Neumonía Viral/virología , Mapeo de Interacción de Proteínas , COVID-19 , Humanos , Glicoproteínas de Membrana/metabolismo , Pandemias , SARS-CoV-2 , Transducción de Señal/genética , Proteínas del Envoltorio Viral
5.
Emerg Infect Dis ; 24(1)2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29076806

RESUMEN

We report partial molecular characterization of isolates from an autochthonous chikungunya virus cluster in Latium Region. E1 sequences from 3 patients differ substantially from sequences from the 2007 outbreak in Italy and lack the A226V substitution associated with increased viral fitness in the Aedes albopictus mosquito vector.


Asunto(s)
Fiebre Chikungunya/epidemiología , Virus Chikungunya , Aedes/virología , Animales , Fiebre Chikungunya/transmisión , Virus Chikungunya/genética , Preescolar , Brotes de Enfermedades/estadística & datos numéricos , Femenino , Humanos , Italia/epidemiología , Masculino , Filogenia , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADN
6.
J Med Virol ; 90(7): 1264-1271, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29611880

RESUMEN

Predictive factors of HCV relapse after treatment with DAAs are poorly understood. In this study, we aimed to assess whether the residual viral load positivity observed during or at the end of treatment (EOT) has an impact on viral outcome. Blood samples were collected from 337 patients with genotypes (GT) 1a, 1b, 2, 3, and 4 HCV chronic infection, treated with DAAs to determine HCV RNA load by the Abbott RealTime HCV (ART) assay at treatment week (W) 4, at EOT, and 4, 12, 24 weeks after discontinuation. EOT and other samples with "detected <12/mL" (DNQ) were retested by an ultrasensitive protocol (USP) to confirm the result. Frequency of DNQ was analyzed in subgroups of patients and clinical conditions to assess potential correlations. At W4, 22% and 30.9% of the samples were undetectable and DNQ by ART assay, respectively, but no correlation for achieving SVR was found. In contrast, an HCV RNA cut-off of ≥50/mL at W4 was a significant predictor of therapy failure (P = 0.036, univariate analysis). At EOT, DNQ was associated to 12W treatment duration (P < 0.001) and GT1a infection (P = 0.036). Overall, 20/41 (48.8%) of DNQ samples at EOT or post-treatment W4, were confirmed by USP but only in a single case the patient experienced viral relapse. HCV RNA at W4 can predict SVR, irrespective to genotype or DAA regimen. HCV RNA DNQ at EOT is associated to shorter treatment duration and to GT1a, but is not a predictor of therapy failure.


Asunto(s)
Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , ARN Viral/sangre , Respuesta Virológica Sostenida , Carga Viral , Monitoreo de Drogas , Femenino , Humanos , Masculino , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
7.
Liver Int ; 38(10): 1741-1750, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29359389

RESUMEN

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is known to cause major alterations in the cross-talk between hepatic and immune cells thus contributing to the liver disease pathogenesis. Extracellular vesicles have been proved to act as major players in cell-cell communication, and their cargo changes in relation to pathophysiological states. The aim of this study was to evaluate the effects of chronic HCV infection and direct-acting antivirals (DAA) on exosome-delivered microRNAs and on their ability to modulate the innate immune response. METHODS: Exosomes isolated from the plasma of healthy donors and naïve, viremic HCV patients before and after DAA treatment have been compared for their microRNAs cargo by quantitative polymerase chain reaction. Functional assays with peripheral blood cells from healthy donors were performed to assess exosome-mediated immune responses. RESULTS: MicroRNAs associated with HCV-related immunopathogenesis which were found to be enriched in exosomes of HCV viremic patients (in particular, miR-122-5p, miR-222-3p, miR-146a, miR-150-5p, miR-30c, miR-378a-3p and miR-20a-5p) were markedly reduced by DAA therapy. This exosome-microRNA cargo modulation parallels changes in their immunomodulatory properties in ex vivo experiments. Exosomes from HCV patients inhibit NK degranulation activity and this effect correlates with miR-122-5p or miR-222-3p levels. CONCLUSIONS: Enrichment of immunomodulatory microRNAs in exosomes of HCV patients was correlated with their inhibitory activity on innate immune cells function. Direct-acting antivirals (DAA) treatment was observed to revert both microRNA content and functional profiles of systemic exosomes towards those of healthy donors. Exosome-associated microRNAs may provide valuable biomarkers to monitor immune response recovery.


Asunto(s)
Antivirales/farmacología , Exosomas/inmunología , Hepatitis C Crónica/tratamiento farmacológico , MicroARNs/inmunología , Adulto , Anciano , Biomarcadores , Estudios de Casos y Controles , Comunicación Celular , Femenino , Perfilación de la Expresión Génica , Hepacivirus/genética , Humanos , Inmunidad Innata , Masculino , Persona de Mediana Edad
9.
Euro Surveill ; 22(34)2017 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-28857045

RESUMEN

We describe the dynamics of dengue virus (DENV) infection in a woman in her mid-30s who developed fever after returning from Sri Lanka to Italy in April 2017. Laboratory testing demonstrated detectable DENV-RNA in plasma, urine, saliva, vaginal secretion. Persistent shedding of DENV-RNA was demonstrated in vaginal secretion, and DENV-RNA was detectable in the pelleted fraction up to 18 days from symptom onset. These findings give new insights into DENV vaginal shedding and vertical transmission.


Asunto(s)
Virus del Dengue/genética , Dengue/diagnóstico , Fiebre/etiología , Viaje , Esparcimiento de Virus , Virus del Dengue/aislamiento & purificación , Femenino , Fiebre/virología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Italia , Reacción en Cadena en Tiempo Real de la Polimerasa , Sri Lanka
10.
Liver Int ; 36(3): 410-7, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26264452

RESUMEN

BACKGROUND AND AIMS: In patients with hepatitis C virus (HCV), recurrence of infection after liver transplant (LT) is universal and associated with worst survival. We present the results of an Italian cohort to compare the 3-year outcome of HCV-Ab-positive and HCV-Ab-negative LT recipients and to assess the potential interaction between HCV-Ab sero-status and other risk factors for LT failure. METHODS: The study is a multicentre cohort including a sample of liver transplant centres. Participant's information was collected at the local level. The best functional form of variables was decided according to the objective methods based on information theory. Association between transplant failure and potential risk factors was assessed in univariate and multivariate Poisson regression model with random intercept. RESULTS: Between June 2007 and May 2009, 1164 LT recipients were enrolled in 16 Italian transplant centres, of them 275 (23.63%) experienced LT failure. Incidence rates of LT failure was 0.32 and 0.23 per 1000 person-days in HCV-Ab-positive and HCV-Ab-negative recipients respectively (P = 0.003). Inferential models according to Akaike information criterion indicated that donor-recipient age difference and donor-recipient sex matching were more informative to predict LT failure than the age and the sex as separate variables. Multivariate analysis provided evidence that HCV-Ab sero-status, time after LT, donor-recipient age difference, donor-recipient sex matching and recipient's MELD score were significantly associated with LT failure. Moreover, the effect of HCV-Ab sero-status on LT failure was modified by the simultaneous action of time after LT and donor-recipient age difference. No interaction was found between recipient's HCV-Ab sero-status and either recipient's MELD or donor-recipient sex matching. CONCLUSION: In view of the imminent introduction of new anti-HCV therapies, our study provides information to assess which LT recipients should be prioritized for receiving these highly effective, but expensive, new treatments. This is particularly relevant for those clinical settings where healthcare prioritization is endorsed by national authorities.


Asunto(s)
Antivirales/uso terapéutico , Enfermedad Hepática en Estado Terminal/cirugía , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Selección de Paciente , Activación Viral , Biomarcadores/sangre , Estudios de Cohortes , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/virología , Femenino , Prioridades en Salud , Hepacivirus/inmunología , Hepacivirus/patogenicidad , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/mortalidad , Anticuerpos contra la Hepatitis C/sangre , Humanos , Italia , Trasplante de Hígado/mortalidad , Masculino , Análisis Multivariante , Factores de Riesgo , Factores de Tiempo , Insuficiencia del Tratamiento
11.
Euro Surveill ; 21(32)2016 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-27541989

RESUMEN

A man in his early 30s reported in January 2016 a history of fever, asthenia and erythematous rash during a stay in Haiti. On his return to Italy, ZIKV RNA was detected in his urine and saliva 91 days after symptom onset, and in his semen on day 188, six months after symptom onset. Our findings support the possibility of sexual transmission of ZIKV and highlight the importance of continuing to investigate non-vector-borne ZIKV infection.


Asunto(s)
Semen/virología , Viaje , Esparcimiento de Virus , Infección por el Virus Zika/diagnóstico , Virus Zika/aislamiento & purificación , Adulto , Astenia/virología , Exantema/virología , Fiebre/virología , Haití , Humanos , Italia , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sexo Seguro , Saliva/virología , Enfermedades Virales de Transmisión Sexual/prevención & control , Esposos , Factores de Tiempo , Orina/virología , Virus Zika/genética , Infección por el Virus Zika/sangre , Infección por el Virus Zika/virología
12.
Int J Mol Sci ; 17(10)2016 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-27739414

RESUMEN

Hepatitis C virus (HCV) is classified into seven phylogenetically distinct genotypes, which are further subdivided into related subtypes. Accurate assignment of genotype/subtype is mandatory in the era of directly acting antivirals. Several molecular methods are available for HCV genotyping; however, a relevant number of samples with indeterminate, mixed, or unspecified subtype results, or even with misclassified genotypes, may occur. Using NS5B direct (DS) and ultra-deep pyrosequencing (UDPS), we have tested 43 samples, which resulted in genotype 1 unsubtyped (n = 17), mixed infection (n = 17), or indeterminate (n = 9) with the Abbott RealTime HCV Genotype II assay. Genotype 1 was confirmed in 14/17 samples (82%): eight resulted in subtype 1b, and five resulted in subtype 1a with both DS and UDPS, while one was classified as subtype 1e by DS and mixed infection (1e + 1a) by UDPS. Three of seventeen genotype 1 samples resulted in genotype 3h with both sequencing approaches. Only one mixed infection was confirmed by UDPS (4d + 1a), while in 88% of cases a single component of the mixture was detected (five genotype 1a, four genotype 1b, two genotype 3a, two genotype 4m, and two genotype 4d); 44% of indeterminate samples resulted genotype 2c by both DS and UDPS, 22% resulted genotype 3a; one indeterminate sample by Abbott resulted in genotype 4d, one resulted in genotype 6n, and one was classified as subtype 3a by DS, and resulted mixed infection (3a + 3h) by UDPS. The concordance between DS and UDPS was 94%, 88%, and 89% for genotype 1, co-infection, and indeterminate results, respectively. UDPS should be considered very useful to resolve ambiguous HCV genotyping results.


Asunto(s)
Hepacivirus/genética , Hepatitis C/virología , Secuenciación de Nucleótidos de Alto Rendimiento , ARN Viral/química , Genotipo , Hepacivirus/metabolismo , Hepatitis C/clasificación , Humanos , Filogenia , ARN Viral/genética , ARN Viral/metabolismo , Juego de Reactivos para Diagnóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Secuencia de ADN , Proteínas no Estructurales Virales/genética
14.
New Microbiol ; 38(4): 565-70, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26485015

RESUMEN

On November 25, 2014, an Italian physician infected by Ebola virus in Sierra Leone was admitted to the "Lazzaro Spallanzani" National Institute for Infectious Diseases in Rome, Italy. He was the first Italian case and was successfully cured in 38 days. The staff responsible for communication had a critical role ensuring that this challenging mission went smoothly. The Institutional Press Office working together with the press offices of the Ministry of Health was able to provide the high level of expertise necessary within both medical and communication contexts. Communication strategy, tools and procedures adopted before and after the arrival of the patient are summarized.


Asunto(s)
Comunicación , Fiebre Hemorrágica Ebola/psicología , Adulto , Ebolavirus/genética , Ebolavirus/aislamiento & purificación , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Fiebre Hemorrágica Ebola/virología , Hospitales , Humanos , Italia , Masculino
15.
New Microbiol ; 38(1): 85-9, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25742151

RESUMEN

Aim of this work was to investigate a possible correlation between the frequency of JCV-specific T-cells and PML occurrence in HIV-infected subjects and in liver transplant recipients. A significant decrease of JCV-specific T-cells was observed in HIV-PML subjects, highlighting a close relation between JCV-specific T-cell immune impairment and PML occurrence in HIV-subjects. Interestingly, liver-transplant recipients (LTR) showed a low frequency of JCV-specific T-cells, similar to HIV-PML subjects. Nevertheless, none of the enrolled LTR developed PML, suggesting the existence of different immunological mechanisms involved in the maintenance of a protective immune response in LTR.


Asunto(s)
Infecciones por VIH/inmunología , Interferón gamma/inmunología , Virus JC/inmunología , Leucoencefalopatía Multifocal Progresiva/inmunología , Trasplante de Hígado , Linfocitos T/inmunología , Adulto , Anciano , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/cirugía , Infecciones por VIH/virología , VIH-1/genética , VIH-1/inmunología , Humanos , Interferón gamma/genética , Virus JC/genética , Virus JC/aislamiento & purificación , Leucoencefalopatía Multifocal Progresiva/etiología , Leucoencefalopatía Multifocal Progresiva/virología , Masculino , Persona de Mediana Edad , Linfocitos T/virología , Receptores de Trasplantes
16.
J Clin Microbiol ; 52(6): 2019-26, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24671791

RESUMEN

Concordance between molecular assays may be suboptimal at low HIV-1 viremia levels (<1,000 copies/ml); therefore, it may be difficult to define and compare virologic endpoints for successful and failed therapy. We compared two commercial assays (the Abbott RealTime HIV-1 and the Roche Cobas AmpliPrep/TaqMan HIV-1 version 2.0) for their ability to detect and quantify low viral loads. A comparison was performed using 167 residual clinical samples (with values ranging from "not detected" to 1,000 copies/ml, as measured by the Abbott assay) and the National Institute and Biological Standards and Control (NIBSC) HIV-1 RNA working reagent 1 for nucleic acid amplification techniques (NAT) assays (serially diluted to a range from 1 to 1,000 copies/ml). Quantitative results were compared using Lin's concordance correlation coefficient and a Bland-Altman plot. Concordance with the qualitative results was measured by Cohen's kappa statistic. With clinical samples, the degree of interassay concordance of the qualitative results at a 40-copies/ml HIV-1 RNA threshold was substantial (κ = 0.762); the correlation among the quantified samples was suboptimal (concordance correlation coefficient, 0.728; P < 0.0001); the mean difference of the values between the Roche and Abbott assays was 0.193 log10 copies/ml. Using the HIV-1 RNA working reagent 1 for NAT assays, the results provided by the Roche assay were, on average, 3 times higher than expected, while the Abbott assay showed high accuracy. The Roche assay was highly sensitive, being able to detect a level as low as 3.5 copies/ml HIV-1 RNA with 95% probability. The performance characteristics of each molecular assay should be taken into account when HIV-1 RNA threshold values for "virologic suppression," "virologic failure," "persistent low viral loads," etc., are defined and indicated in the support of clinical decisions.


Asunto(s)
Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Técnicas de Diagnóstico Molecular/métodos , ARN Viral/sangre , Carga Viral/métodos , Humanos , Sensibilidad y Especificidad
17.
J Antimicrob Chemother ; 69(11): 3085-94, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25015667

RESUMEN

OBJECTIVES: Tropism evolution of HIV-1 quasispecies was analysed by ultra-deep pyrosequencing (UDPS) in patients on first-line combination antiretroviral therapy (cART) always suppressed or experiencing virological failure episodes. METHODS: Among ICONA patients, two groups of 20 patients on cART for ≥5 years, matched for baseline viraemia and therapy duration, were analysed [Group I, patients always suppressed; and Group II, patients experiencing episode(s) of virological failure]. Viral tropism was assessed by V3 UDPS on plasma RNA before therapy (T0) and on peripheral blood mononuclear cell proviral DNA before-after therapy (T0-T1), using geno2pheno false positive rate (FPR) (threshold for X4: 5.75). For each sample, quasispecies tropism was assigned according to X4 variant frequency: R5, <0.3% X4; minority X4, 0.3%-19.9% X4; and X4, ≥20% X4. An R5-X4 switch was defined as a change from R5/minority X4 in plasma/proviral genomes at T0 to X4 in provirus at T1. RESULTS: At baseline, mean FPR and %X4 of viral RNA were positively correlated with those of proviral DNA. After therapy, proviral DNA load significantly decreased in Group I; mean FPR of proviral quasispecies significantly decreased and %X4 increased in Group II. An R5-X4 switch was observed in five patients (two in Group I and three in Group II), all harbouring minority X4 variants at T0. CONCLUSIONS: UDPS analysis reveals that the tropism switch is not an 'on-off' phenomenon, but may result from a profound re-shaping of viral quasispecies, even under suppressive cART. However, episodes of virological failure seem to prevent reduction of proviral DNA and to accelerate viral evolution, as suggested by decreased FPR and increased %X4 at T1 in Group II patients.


Asunto(s)
Antirretrovirales/administración & dosificación , Evolución Molecular , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , VIH-1/genética , Tropismo/genética , Adulto , Estudios de Cohortes , Quimioterapia Combinada , Femenino , VIH-1/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Tropismo/efectos de los fármacos , Carga Viral/efectos de los fármacos , Carga Viral/genética
18.
Emerg Infect Dis ; 19(1): 110-4, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23260079

RESUMEN

During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries.


Asunto(s)
Brotes de Enfermedades , Genotipo , Virus de la Hepatitis E/genética , Hepatitis E/epidemiología , ARN Viral/genética , Adulto , Anciano , China , Hepatitis E/virología , Virus de la Hepatitis E/clasificación , Virus de la Hepatitis E/aislamiento & purificación , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Tipificación Molecular , Filogenia , Filogeografía , ARN Viral/clasificación , ARN Viral/aislamiento & purificación
19.
New Microbiol ; 36(4): 353-61, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24177297

RESUMEN

Identification of recent infections (RI) may contribute to improve the quality of human immunodeficiency virus (HIV) surveillance, monitoring ongoing transmission and planning and evaluating prevention programs. Our study applied an algorithm combining clinical and serological information to identify RI in individuals newly diagnosed with HIV in Rome, during the years 1999-2008, in order to describe the trend and characteristics of recently infected individuals. RI were documented seroconverters, or people with an HIV avidity index (AI)<0.80. Individuals with advanced infection (CD4 count <200 cells/?L or AIDS-defining illness) or with AI ?0.80 were considered long-standing infections. Overall, we observed 2,563 new HIV diagnoses. The algorithm was applied in 2124/2563 (82.9%). Of these, 355 were RI (16.7%). RI was found independently associated with calendar year (adjusted odds ratio [aOR]= 1.06, 95% confidence intervals [CI]=[CI 1.02-1.11], for every year of increase), HIV-risk category (men having sex with men: aOR=1.44, [CI 1.04-1.98]; injecting drug users: aOR=1.58, [CI 1.03-2.42] vs. heterosexuals), country of origin (foreign-born: vs Italians: aOR=0.46, [CI 0.33-0.62]), and recruitment site (inpatient vs outpatient clinic: aOR=0.49, [CI 0.37-0.66]). By the application of our algorithm we could characterize the pattern of ongoing HIV transmission, identifying groups needing more urgent prevention programs.


Asunto(s)
Infecciones por VIH/diagnóstico , VIH-1/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Conducta Sexual , Adulto Joven
20.
J Med Virol ; 84(6): 839-44, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22996031

RESUMEN

Viral quasispecies population dynamics between monocytes and T-lymphocytes were analyzed in patients after highly active antiretroviral therapy (HAART) interruption, during a follow-up of 3-6 months. V3 env region underwent ultra-deep pyrosequencing. Co-receptor usage prediction was performed by Position Specific Score Matrix Analysis. Phylogenetic trees were constructed to evaluate the relationships between the variants. Gene flow was also investigated. Even though at the moment of therapy interruption monocyte-derived HIV-1 genomes presented higher genetic heterogeneity than that of T-lymphocytes, at subsequent times, this difference in genetic heterogeneity disappeared, due to different waves of expansion and reduction of quasispecies variability associated with monocytes and T-lymphocytes. Phylogenetic analysis and gene flow evaluation supported the hypothesis of extensive interchange of variants between cellular compartments of the infection. A spread of proviral X4 lineages hidden in monocytes to T cells was observed, but this was not associated with an overall shift towards CXCR4 using variants during the observation period.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Variación Genética , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Monocitos/virología , Linfocitos T/virología , Esquema de Medicación , Proteína gp120 de Envoltorio del VIH/genética , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/metabolismo , Humanos , Fragmentos de Péptidos/genética , Filogenia , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Análisis de Secuencia de ADN
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