Genetic Characterization of Human T-Cell Lymphotropic Virus Type 1 in Mozambique: Transcontinental Lineages Drive the HTLV-1 Endemic

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of Adult T-Cell Leukemia/Lymphoma (ATL), the Tropical Spastic Paraparesis/HTLV-1-associated Myelopathy (TSP/HAM) and other inflammatory diseases, including dermatitis, uveitis, and myositis. It is estimated that 2–8% of the infected persons will develop a HTLV-1-associated disease during their lifetimes, frequently TSP/HAM. Thus far, there is not a specific treatment to this progressive and chronic disease. HTLV-1 has means of three transmission: (i) from mother to child during prolonged breastfeeding, (ii) between sexual partners and (iii) through blood transfusion. HTLV-1 has been characterized in 7 subtypes and the geographical distribution and the clinical impact of this infection is not well known, mainly in African population. HTLV-1 is endemic in sub-Saharan Africa. Mozambique is a country of southeastern Africa where TSP/HAM cases were reported. Recently, our group estimated the HTLV prevalence among Mozambican blood donors as 0.9%. In this work we performed a genetic analysis of HTLV-1 in blood donors and HIV/HTLV co-infected patients from Maputo, Mozambique. Our results showed the presence of three HTLV-1 clusters within the Cosmopolitan/Transcontinental subtype/subgroup. The differential rates of HIV-1/HTLV-1 co-infection in the three HTLV-1 clusters demonstrated the dynamic of the two viruses and the need for implementation of control measures focusing on both retroviruses

Co-infection by human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia virus type 1 (HTLV-1): does immune activation lead to a faster progression to AIDS?

<p>Abstract</p> <p>Background</p> <p>Recent data have shown that HTLV-1 is prevalent among HIV positive patients in Mozambique, although the impact of HTLV-1 infection on HIV disease progression remains controversial. Our aim was to determine the phenotypic profile of T lymphocytes subsets among Mozambican patients co-infected by HIV and HTLV-1.</p> <p>Methods</p> <p>We enrolled 29 patients co-infected by HTLV-1 and HIV (co-infected), 59 patients mono-infected by HIV (HIV) and 16 healthy controls (HC), respectively.</p> <p>For phenotypic analysis, cells were stained with the following fluorochrome-labeled anti-human monoclonal antibodies CD4-APC, CD8-PerCP, CD25-PE, CD62L-FITC, CD45RA-FITC. CD45RO-PE, CD38-PE; being analysed by four-colour flow cytometry.</p> <p>Results</p> <p>We initially found that CD4⁺T cell counts were significantly higher in co-infected, as compared to HIV groups. Moreover, CD4⁺T Lymphocytes from co-infected patients presented significantly higher levels of CD45RO and CD25, but lower levels of CD45RA and CD62L, strongly indicating that CD4⁺T cells are more activated under HTLV-1 plus HIV co-infection.</p> <p>Conclusion</p> <p>Our data indicate that HTLV-1/HIV co-infected patients progress with higher CD4⁺T cell counts and higher levels of activation markers. In this context, it is conceivable that in co-infected individuals, these higher levels of activation may account for a faster progression to AIDS.</p

EM TEMPOS GLOBAIS, UM “NOVO” LOCAL: a Ford na Bahia

O artigo analisa a dinâmica da Região Metropolitana de Salvador (RMS) a partir da implantação da Ford, discutindo a perspectiva do ‘lugar’ (a periferia metropolitana), dentro de uma relação assimétrica com os negócios globais na era da flexibilidade. O texto caracteriza o complexo Ford de Camaçari a partir da reestruturação produtiva e das mudanças na organização e funcionamento dos territórios e, na segunda parte, seus impactos sobre a periferia metropolitana de Salvador. Na conclusão demonstra que as mesmas circunstâncias que permitiram a vinda da montadora para Camaçari constrangem as ambições originais de melhor equacionamento entre crescimento econômico e progresso social: a flexibilidade dos novos arranjos, que tornam os espaços periféricos estratégicos, compromete o “enraizamento” do investimento; a “produção enxuta”, exígua de emprego e diligente na sua precarização, inibe os benefícios sociais. PALAVRAS CHAVE: reestruturação produtiva, mercado de trabalho, indústria automobilística, periferia metropolitana, segregação socioespacial. IN GLOBAL TIMES, A “NEW” PLACE: Ford in Bahia Ângela Franco This paper makes an analysis of the dynamics of the Metropolitan Area of Salvador (in Portuguese, RMS) starting from the implantation of Ford, discussing the perspective of the ‘local’ (the metropolitan periphery), inside of an asymmetrical relationship with global businesses in the age of flexibility. The Ford Automotive Compound is caracterized in the first part of the paper from its productive reestructuring and changes in the organization and work of territories, and, in the second part, from its impact on the the metropolitan periphery from Salvador. In its conclusion it demonstrates that the same circumstances that allowed the arrival of the automotive maker in Camaçari constrain the original ambitions of better ratio between economical growth and social progress: the flexibility of the new automotive production methods, making peripheric spaces strategic, compromises on the permanence of the investments; and the “streamlined production”, easy on job production and hard on job flexibilization inhibit social benefits. KEYWORDS: productive restructuring, job market, automobile industry, metropolitan periphery, socioespatial segregation. EN PERIODE DE MONDIALISATION, UN “NOUVEAU” LOCAL: Ford à Bahia Ângela Franco Cet article traite de l’analyse de la dynamique de la Région Métropolitaine de Salvador (RMS), à partir de l’implantation de l’usine Ford. On y discute de la perspective du “lieu” (la périphérie métropolitaine), dans une relation asymétrique avec les affaires globales à une époque de flexibilité. On y caractérise le complexe Ford de Camaçari à partir de la restructuration productive et des changements dans l’organisation et le fonctionnement des territoires. Ses impacts sur la périphérie métropolitaine de Salvador sont présentés dans la deuxième partie. En conclusion, on y démontre que ce sont les mêmes circonstances qui ont permis l’arrivée de l’usine de montage à Camaçari qui représentent une contrainte pour les ambitions qui, à l’origine, voulaient atteindre une meilleure équation entre la croissance économique et le progrès social. La flexibilité de ces nouveaux arrangements, qui rendent les espaces périphériques stratégiques, compromet “l’enracinement” des investissements, la “production exiguë”, l’exiguïté des emplois et la diligence dans leur précarisation, elle inhibe les avantages sociaux. MOTS-CLÉS: restructuration productive, marché du travail, industrie automobile, périphérie métropolitaine, ségrégation sociale et spatiale. Publicação Online do Caderno CRH: http://www.cadernocrh.ufba.b

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).</jats:sec

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

HIV-1 Nef Inhibits Protease Activity and Its Absence Alters Protein Content of Mature Viral Particles

<div><p>Nef is an important player for viral infectivity and AIDS progression, but the mechanisms involved are not completely understood. It was previously demonstrated that Nef interacts with GagPol through p6*-Protease region. Because p6* and Protease are involved in processing, we explored the effect of Nef on viral Protease activity and virion assembly. Using in vitro assays, we observed that Nef is highly capable of inhibiting Protease activity. The IC50 for <i>nef</i>-deficient viruses in drug susceptibility assays were 1.7- to 3.5-fold higher than the wild-type counterpart varying with the type of the Protease inhibitor used. Indicating that, in the absence of Nef, Protease is less sensitive to Protease inhibitors. We compared the protein content between wild-type and <i>nef</i>-deficient mature viral particles by gradient sedimentation and observed up to 2.7-fold reduction in the Integrase levels in <i>nef</i>-deficient mature particles. This difference in levels of Integrase correlated with the difference in infectivity levels of wild type and <i>nef</i>-deficient viral progeny. In addition, an overall decrease in the production of mature particles was detected in <i>nef</i>-deficient viruses. Collectively, our data support the hypothesis that the decreased infectivity typical of <i>nef</i>-deficient viruses is due to an abnormal function of the viral Protease, which is in turn associated with less mature particles being produced and the loss of Integrase content in these particles, and these results may characterize Nef as a regulator of viral Protease activity.</p></div

Impact of Nelfinavir Resistance Mutations on In Vitro Phenotype, Fitness, and Replication Capacity of Human Immunodeficiency Virus Type 1 with Subtype B and C Proteases

Human immunodeficiency virus type 1 subtype B and C proteases were manipulated to contain 90M, 88D, or 89L, and their in vitro biological properties were studied. We showed that D30N has significantly more impact in subtype C than in subtype B counterparts, accounting for the reported low prevalence of this mutation in patients failing nelfinavir-based regimens