Genetic divergence of HIV-1 B subtype in Italy over the years 2003-2016 and impact on CTL escape prevalence.
Ontology highlight
ABSTRACT:
SUBMITTER: Alteri C
PROVIDER: S-EPMC6200748 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
Publications
Genetic divergence of HIV-1 B subtype in Italy over the years 2003-2016 and impact on CTL escape prevalence.
Alteri Claudia C Fabeni Lavinia L Scutari Rossana R Berno Giulia G Di Carlo Domenico D Gori Caterina C Bertoli Ada A Vergori Alessandra A Mastrorosa Ilaria I Bellagamba Rita R Mussini Cristina C Colafigli Manuela M Montella Francesco F Pennica Alfredo A Mastroianni Claudio Maria CM Girardi Enrico E Andreoni Massimo M Antinori Andrea A Svicher Valentina V Ceccherini-Silberstein Francesca F Perno Carlo Federico CF Santoro Maria Mercedes MM
Scientific reports 20181024 1
HIV-1 is characterized by high genetic variability, with implications for spread, and immune-escape selection. Here, the genetic modification of HIV-1 B subtype over time was evaluated on 3,328 pol and 1,152 V3 sequences belonging to B subtype and collected from individuals diagnosed in Italy between 2003 and 2016. Sequences were analyzed for genetic-distance from consensus-B (Tajima-Nei), non-synonymous and synonymous rates (dN and dS), CTL escapes, and intra-host evolution over four time-spans ...[more]
Similar Datasets
Project description:BackgroundThe surveys in this study were carried out at the Graduate Medical Education Division at Oregon Health & Science University (OHSU). OHSU implemented two significant wellness initiatives: a wellness program in 2004, and a policy allowing 4 half-days off each academic year to pursue personal or family health care needs in 2010. This study provides a secondary data analysis of five cross-sectional surveys of career satisfaction of resident and fellow trainees.MethodsAll trainees were surveyed five times over a 10-year period using anonymous, cross-sectional web-based survey instruments. Surveys included questions about career satisfaction, perceived stress, sleep hours, burnout, and related factors.ResultsThis represents 10 years of accumulated responses from over 2,200 residents with results showing continual improvement in their career satisfaction. Response rates ranged from 56% to 72%. During the study period, there was a significant positive change in overall resident career satisfaction, with little change in factors traditionally considered to be predictive of overall career satisfaction such as sleep hours or perceived stress level. In addition, our data support that availability of time for personal tasks could positively impact the overall training experience.ConclusionWe postulate that the improvements in satisfaction relate to two major institutional innovations designed to promote resident wellness.
| S-EPMC5538544 | biostudies-literature
Project description:Universal varicella vaccination in Sicily was introduced in infant population since 2003, with a rapidly increasing coverage. Aim of the present study was to analyze changes in the epidemiology of varicella since the introduction of universal vaccination.The study was performed by analyzing Sicilian administrative/clinical data on varicella case notifications and hospitalizations from 2003 to 2012 (ICD-9-CM discharge diagnosis codes 052 and 052.×). MMR+V and V coverage were also calculated for each birth cohort. Moreover, blood samples drawn in 2013/2014 from general population stratified by age were tested for varicella antibodies.From 2003 to 2012, 15 433 varicella cases were notified with a decreasing temporal trend (1.1/1000 population in 2003 to 0.1/1000 in 2012) (P < 0.001). In the same period, a total of 1145 patients were hospitalized with a diagnosis of varicella, with a 6-fold reduced risk of hospitalization over time (from 4.8 to 0.8/100 000 population per year; P < 0.001). Varicella vaccination coverage rates increased from 40% (2001 birth cohort) to 85% (2010 birth cohort), and inversely correlated with both notification and hospitalization rates (P < 0.001). Finally, 80.0% of subjects enrolled in the seroepidemiological survey were positive for varicella and seroprevalence increased significantly with age in both sexes (P < 0.001).The results show the impact of infant universal varicella vaccination in Sicily. Noteworthy, notifications and hospitalizations for varicella have significantly decreased after the introduction of universal vaccination, confirming the effectiveness of the adopted strategy.
| S-EPMC4514146 | biostudies-other
Project description:The existence of viral variants that escape from the selection pressures imposed by cytotoxic T-lymphocytes (CTLs) in HIV-1 infection is well documented, but it is unclear when they arise, with reported measures of the time to escape in individuals ranging from days to years. A study of participants enrolled in the SPARTAC (Short Pulse Anti-Retroviral Therapy at HIV Seroconversion) clinical trial allowed direct observation of the evolution of CTL escape variants in 125 adults with primary HIV-1 infection observed for up to three years. Patient HLA-type, longitudinal CD8+ T-cell responses measured by IFN-? ELISpot and longitudinal HIV-1 gag, pol, and nef sequence data were used to study the timing and prevalence of CTL escape in the participants whilst untreated. Results showed that sequence variation within CTL epitopes at the first time point (within six months of the estimated date of seroconversion) was consistent with most mutations being transmitted in the infecting viral strain rather than with escape arising within the first few weeks of infection. Escape arose throughout the first three years of infection, but slowly and steadily. Approximately one third of patients did not drive any new escape in an HLA-restricted epitope in just under two years. Patients driving several escape mutations during these two years were rare and the median and modal numbers of new escape events in each patient were one and zero respectively. Survival analysis of time to escape found that possession of a protective HLA type significantly reduced time to first escape in a patient (p = 0.01), and epitopes escaped faster in the face of a measurable CD8+ ELISpot response (p = 0.001). However, even in an HLA matched host who mounted a measurable, specific, CD8+ response the average time before the targeted epitope evolved an escape mutation was longer than two years.
| S-EPMC4333731 | biostudies-literature
Project description:BackgroundFew data are available about temporal trends of antibiotic use in hospitalized children. The aim of the current study was to investigate the pattern and trends of antibiotic use over the years 2008-2016 in the largest children's hospital in Italy.MethodsAnnual point prevalence surveys of antibiotic use were conducted by reviewing medical charts of 0-17 year-old children hospitalized for ≥48 h. Prevalence of antibiotic use was computed by year, type of ward and indication. Trends in prevalence over time were evaluated using the Cochrane-Armitage test. Possibile determinants of antibiotic use were assessed at univariate analysis and through a logistic regression model.ResultsOut of 3015 children, 1516 (50.3%) received antibiotics, 58.1% of which for medical/surgical prophylaxis. Prevalence of antibiotic use increased from 42.0% in 2008 to 56.2% in 2016 (p = 0.001). The prevalence of patients receiving antibiotics for medical prophylaxis increased from 6.1% in 2008 to 24.2% in 2016 (p < 0.001), whereas the prevalence of patients receiving antibiotics for surgical prophylaxis significantly decreased (from 13.7 to 11.8%; p = 0.04); no significant temporal trends were found in antibiotic use for treating infections. The administration of third-generation cephalosporins for surgical and medical prophylaxis significantly decreased over time, while the proportion of antibiotics prescribed to treat infections after microbiological investigations significantly increased. Year (ORadj: 1.8 in 2016 compared to 2008, p < 0.001), age (ORadj ≥1.5 in children ≥1 year, compared to infants ≤2 months, p < 0.001), length of stay (LOS) (ORadj: 1.4 in case of LOS between 8 and 30 days compared to LOS ≤ 7 days, p < 0.001), and type of ward (ORadj: ≥1.3 in intensive-care, surgical and medical-subspecialty units compared to medical units, p < 0.001) were significantly and independently associated with antibiotic use.ConclusionsComparing prevalence rates of antibiotic use among hospitals and over time should consider differences in patient characteristics, such as age, ward of hospitalization and length of stay. Over the years, we documented an improvement in the choice of antibiotics prescribed for medical and surgical prophylaxis. However, further efforts are needed to avoid antibiotic misuse for medical prophylaxis, and to reduce the empirical use of broad spectrum antibiotics.
| S-EPMC6528368 | biostudies-literature
Project description:The Rakai Community Cohort Study in south central Uganda has surveyed people aged 15-49 since 1994. Antiretroviral therapy (ART) was introduced in 2004. HIV p24 and gp41 subtype distribution and viral diversity were studied from blood samples collected at three surveys in 1994-1995, 2002-2003, and 2008-2009, which were compared with a new survey round from 2011 to 2012. These included 1364 HIV+ individuals. For both p24 and gp41 domains, the genetic diversity within subtypes A and D was significantly increasing in the pre-ART era and decreased between the last two survey rounds in the ART era (p < .01). This study suggests that despite ongoing mixing of viral subtypes, an association with the introduction of ART to a reduction of intra-subtype viral genomic diversity may be occurring, which can be explored in ongoing studies.
| S-EPMC7476391 | biostudies-literature
Project description:ObjectiveTo evaluate cancer risk among individuals with connective tissue disease (CTD) in Friuli Venezia Giulia, northern Italy.MethodsA population-based cohort study was conducted based on data from health records available in the regional healthcare database. Demographic characteristics, hospital discharges, exemption from medical charges, drug prescriptions, were individually matched with data from the population-based cancer registry. Cancer risk was assessed in people diagnosed with the following diseases: systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), systemic sclerosis (SSc), polymyositis (PM), and dermatomyositis (DM).ResultsIn all, 2504 patients were followed for a total of 18,006 person-years (median follow-up: 6.8 years). After 5 and 10 years of follow-up, the cumulative cancer incidence was 2.6% and 8.5%, respectively. The most common cancers were breast (n = 34), lung (n = 24), colon-rectum-anus (n = 20), and non-Hodgkin lymphomas (NHL) (n = 20). Overall, no excess cancer risk was noted (SIR = 0.87), whereas the number of observed NHL cases was more than two-fold significantly higher than expected (SIR = 2.52). The subgroup analysis showed a higher risk of NHL among SS patients (SIR = 3.84) and SLE patients (SIR = 2.69). Conversely, the study population showed a decreased risk for breast cancers (SIR = 0.61) and corpus uteri (SIR = 0.21).ConclusionsThe incidence of NHL was higher among patients with SS and SLE. Careful surveillance for hematological malignancies in these patients is recommended.
| S-EPMC9332163 | biostudies-literature
Project description:INTRODUCTION: Information on temporal trends can identify groups of people at risk for any particular condition; however information on temporal trends on migraine headache at population levels is scarce. Our aim was to estimate the time trends in the prevalence of migraine from 2003 to 2012 in Spain. METHODS: A population-based national study was conducted. We analyzed data using individualized information taken from national surveys conducted in 2003/4, 2006/7, 2009/10 and 2011/12. A total of 94,158 Spanish adults participated. We considered the presence of self-rated and diagnosed migraine, and we analyzed socio-demographic features, lifestyle habits, self-rated health status, and comorbid diseases using logistic regressions. RESULTS: The prevalence of migraine increased from 6.54% in 2003 to 9.69% in 2012 with significant time trends (adj. OR 1.65; 95%CI 1.50-1.81). The probability of women of suffering migraine was 3 times higher than for men (adj.OR 3.08; 2.82-3.37). There was a declining trend in migraine prevalence as age increased (adj.OR 0.42; 0.35-0.51). Demographic variables associated with migraine were lower educational level (adj.OR 1.32; 1.13-1.54) and not being an immigrant (adj.OR 1.37; 1.15-1.64). A worse self-reported health status was related to higher prevalence of migraine (adj.OR 2.83; 2.59-3.09). The prevalence of migraine also increased as the number of comorbid conditions increased (adj.OR 2.42; 2.05-2.86). CONCLUSION: The prevalence of migraine has increased in the first decade of the 21st century in Spain. Migraine was associated with being female, mid-age, low educational level, not being an immigrant, worse self-rated health status and presence of comorbid conditions.
| S-EPMC4208769 | biostudies-other
Project description:Cytotoxic CD8+ T cells (CTLs) play a critical role in controlling viral infections. HIV-infected individuals develop CTL responses against epitopes derived from viral proteins, but also against cryptic epitopes encoded by viral alternative reading frames (ARF). We studied here the mechanisms of HIV-1 escape from CTLs targeting one such cryptic epitope, Q9VF, encoded by an HIVgag ARF and presented by HLA-B*07. Using PBMCs of HIV-infected patients, we first cloned and sequenced proviral DNA encoding for Q9VF. We identified several polymorphisms with a minority of proviruses encoding at position 5 an aspartic acid (Q9VF/5D) and a majority encoding an asparagine (Q9VF/5N). We compared the prevalence of each variant in PBMCs of HLA-B*07+ and HLA-B*07- patients. Proviruses encoding Q9VF/5D were significantly less represented in HLA-B*07+ than in HLA-B*07- patients, suggesting that Q9FV/5D encoding viruses might be under selective pressure in HLA-B*07+ individuals. We thus analyzed ex vivo CTL responses directed against Q9VF/5D and Q9VF/5N. Around 16% of HLA-B*07+ patients exhibited CTL responses targeting Q9VF epitopes. The frequency and the magnitude of CTL responses induced with Q9VF/5D or Q9VF/5N peptides were almost equal indicating a possible cross-reactivity of the same CTLs on the two peptides. We then dissected the cellular mechanisms involved in the presentation of Q9VF variants. As expected, cells infected with HIV strains encoding for Q9VF/5D were recognized by Q9VF/5D-specific CTLs. In contrast, Q9VF/5N-encoding strains were neither recognized by Q9VF/5N- nor by Q9VF/5D-specific CTLs. Using in vitro proteasomal digestions and MS/MS analysis, we demonstrate that the 5N variation introduces a strong proteasomal cleavage site within the epitope, leading to a dramatic reduction of Q9VF epitope production. Our results strongly suggest that HIV-1 escapes CTL surveillance by introducing mutations leading to HIV ARF-epitope destruction by proteasomes.
| S-EPMC3093368 | biostudies-literature
Project description:As human immunodeficiency virus (HIV) begins to replicate within hosts, immune responses are elicited against it. Escape mutations in viral epitopes-immunogenic peptide parts presented on the surface of infected cells-allow HIV to partially evade these responses, and thus rapidly go to fixation. The faster they go to fixation, i.e., the higher their escape rate, the larger the selective pressure exerted by the immune system is assumed to be. This relation underpins the rationale for using escapes to assess the strength of immune responses. However, escape rate estimates are often obtained by employing an aggregation procedure, where several mutations that affect the same epitope are aggregated into a single, composite epitope mutation. The aggregation procedure thus rests upon the assumption that all within-epitope mutations have indistinguishable effects on immune recognition. In this study, we investigate how violation of this assumption affects escape rate estimates. To this end, we extend a previously developed simulation model of HIV that accounts for mutation, selection, and recombination to include different distributions of fitness effects (DFEs) and inter-mutational genomic distances. We use this discrete time Wright-Fisher based model to simulate early within-host evolution of HIV for DFEs and apply standard estimation methods to infer the escape rates. We then compare true with estimated escape rate values. We also compare escape rate values obtained by applying the aggregation procedure with values estimated without use of that procedure. We find that across the DFEs analyzed, the aggregation procedure alters the detectability of escape mutations: large-effect mutations are overrepresented while small-effect mutations are concealed. The effect of the aggregation procedure is similar to extracting the largest-effect mutation appearing within an epitope. Furthermore, the more pronounced the over-exponential decay of the DFEs, the more severely true escape rates are underestimated. We conclude that the aggregation procedure has two main consequences. On the one hand, it leads to a misrepresentation of the DFE of fixed mutations. On the other hand, it conceals within-epitope interactions that may generate irregularities in mutation frequency trajectories that are thus left unexplained.
| S-EPMC5410659 | biostudies-literature
Project description:BACKGROUND/AIMS:In the coming two decades significant increases in the burden of blindness are anticipated unless concerted efforts are made to improve eye care in developing countries. Evidence of changing prevalence rates or numbers of blind people are few. The change in blindness prevalence and the number of blind people in an adult population of Malawi was measured over a 16 year period. METHODS:In 1999 a population based survey of blindness in adults (age 50+) was conducted in Chikwawa district of Malawi. Visual acuity and cause of vision loss were recorded for each eye independently. Blindness was defined as presenting better eye vision of <6/60. Findings from a 1983 survey of blindness in the same district (using similar methods) were re-analysed to be comparable with the survey conducted in 1999. RESULTS:Among 1630 enumerated adults 89% were examined. The age adjusted prevalence of blindness in the adult population was 5.4% and more common in women than men. In each age group the prevalence of blindness was lower in 1999 than in 1983; the overall reduction in blindness was 31%. During this period the 50+ population in Malawi increased almost twofold. Extrapolating the Chikwawa district data to the Malawi population reveals that the number of blind people has increased by 24%; the increase is primarily because of the large increase in the size of the most elderly group, aged 70 and above. CONCLUSION:The majority of blind people in Chikwawa (1983 and 1999) are in the age group 70 and over. This group has had the largest proportional increase in population size in this time. Services in this population have improved in the intervening 16 years and yet there was still an increase in the number of blind people. There was little change in excess blindness in women, suggesting that the same barriers that prevented utilisation of services in 1983 probably persist in 1999. Efforts to reach the most elderly and to reach women are needed to lead to a reduction in blind people in settings such as rural Malawi.
| S-EPMC1771870 | biostudies-literature