FF - CiênciaVitae - Faculdade de Farmácia
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- Evaluation of the clinical sensitivities of three viral load assays with plasma samples from a pediatric population predominantly infected with human immunodeficiency virus type 1 subtype G and BG recombinant formsPublication . Antunes, Rute; Figueiredo, Sofia; Bártolo, Inês; Pinheiro, Manuel; Rosado, Lino; Soares, Isabel; Lourenço, Helena; Taveira, NunoThe viral load assays AMPLICOR HIV-1 Monitor Test 1.5, Nuclisens HIV-1 QT, and Quantiplex HIV RNA 3.0 (bDNA) were evaluated for their abilities to quantify human immunodeficiency virus type 1 (HIV-1) RNA in 64 plasma samples from 21 children infected in Portugal. The children were infected with HIV-1 subtypes A1, B, F1, G, and BG recombinant virus. AMPLICOR v1.5 and Quantiplex v3.0 detected all samples, and there was a good correlation of results between the two kits. Thirty-eight specimens containing HIV-1 subtype B, G, or recombinant BG, could not be detected by Nuclisens HIV-1 QT. We also evaluated the new Retina HIV-1 assay on 21 samples that were HIV-1 positive; Retina HIV-1 failed to detect 5 of 11 subtype G specimens. AMPLICOR v1.5 and Quantiplex v3.0 assays may be used for HIV-1 RNA quantification in Portugal, whereas an improvement in sensitivity for subtype G and recombinant BG is required for Nuclisens HIV-1 QT and Retina HIV-1.
- Um caso de SIDA seronegativoPublication . Cardoso, Ana Rita; Gonçalves, Cristina; Pascoalinho, Dulce; Gil, Carla; Ferreira, António Fernandes; Bártolo, Inês; Taveira, NunoOs A.A. descrevem o caso de uma jovem que se apresenta com um quadro clínico de SIDA e com testes serológicos para o VIH repetidamente negativos. O diagnóstico da infecção pelo VIH-1 foi feito por determinação do Ag p24 e da carga viral por reacção de polimerização enzimática em cadeia (PCR). O parceiro sexual da doente era seropositivo para o VIH-1 e ambos estavam infectados pelo mesmo vírus, um recombinante entre os subtipos A e D. As disparidades encontradas entre este casal sugerem a existência de um defeito imunológico específico que impossibilita o desenvolvimento de anticorpos.
- Seronegative infection and AIDS caused by an A2 subsubtype HIV-1Publication . Cardoso, Ana Rita; Gonçalves, Cristina; Pascoalinho, Dulce; Gil, Catarina; Ferreira, António Fernandes; Bártolo, Inês; Taveira, NunoThe study of true seronegative HIV-1 infections may have important implications for the diagnosis and prevention of HIV-1 infection. The case of an AIDS patient with persistently negative HIV serology is described. Genetic and phylogenetic analysis indicated that she was infected with an A2 subsubtype HIV-1 transmitted by her seropositive and asymptomatic sexual partner. The clinical and serological discordant results suggest the presence of an immunological deficiency that prevents the formation of HIV-1-specific antibodies.
- High genetic diversity of human immunodeficiency virus type 1 in AngolaPublication . Bártolo, Inês; Epalanga, Marta; Bartolomeu, José; Fonseca, Marlene; Mendes, Ana; Gama, António; Taveira, NunoTo investigate which HIV-1 genetic forms are circulating in Angola, we have determined the gag and/or env genotypes of 48 isolates from patients living in Cabinda and Luanda provinces. The following subtypes were identified: A1 (18 samples, 38%), C (7, 15%), H (5, 10%), J (3, 6%), G (2, 4%), A2 (2, 4%), F1 (1, 2%), and D (1, 2%). The env gene fragment was untypable in one sample. Discordant subtype classifications in the gag and env genes were found in eight (17%) samples. There were six different recombination patterns (gag/env): A1/H (3, 6%), A1/G (1, 2%), C/A2 (1, 2%), F1/B (1, 2%), G/B (1, 2%), and G/H (1, 2%). The A1/H recombinant may represent a new circulating recombinant form. The marked genetic heterogeneity of HIV-1 in Angola has important implications for vaccine development.
- A new algorithm for cluster analysis of genomic methylation: the Helicobacter pylori casePublication . Vale, Filipa F.; Encarnação, P.; Vítor, Jorge M. B.Motivation: The genomic methylation analysis is useful to type bacteria that have a high number of expressed type II methyltransferases. Methyltransferases are usually committed to Restriction and Modification (R-M) systems, in which the restriction endonuclease imposes high pressure on the expression of the cognate methyltransferase that hinder R-M system loss. Conventional cluster methods do not reflect this tendency. An algorithm was developed for dendrogram construction reflecting the propensity for conservation of R-M Type II systems. Results: The new algorithm was applied to 52 Helicobacter pylori strains from different geographical regions and compared with conventional clustering methods. The algorithm works by first grouping strains that share a common minimum set of R-M systems and gradually adds strains according to the number of the R-M systems acquired. Dendrograms revealed a cluster of African strains, which suggest that R-M systems are present in H.pylori genome since its human host migrates from Africa. Availability: The software files are available at http://www.ff.ul.pt/paginas/jvitor/Bioinformatics/MCRM_algorithm.zip Supplementary information: Supplementary data are available at Bioinformatics online.
- Antiretroviral drug resistance surveillance among treatment-naive human immunodeficiency virus type 1-infected individuals in Angola: Evidence for low level of transmitted drug resistancePublication . Bártolo, Inês; Rocha, Cheila; Bartolomeu, José; Gama, António; Fonseca, Marlene; Mendes, Ana; Cristina, Filipa; Thamm, Sven; Epalanga, Marta; Silva, Patrícia Cavaco; Taveira, NunoThe prevalence of transmitted human immunodeficiency virus type 1 drug resistance in Angola in 2001 in 196 untreated patients was investigated. All subtypes were detected, along with unclassifiable and complex recombinant strains. Numerous new polymorphisms were identified in the reverse transcriptase and protease. Two (1.6%) unrelated patients harbored nucleoside reverse transcriptase inhibitor- and nonnucleoside reverse transcriptase inhibitor-resistant viruses (mutations: M41L, D67N, M184V, L210W, T215Y or T215F, and K103N). Continued surveillance of drug resistance is required for maximization of ART efficacy in Angola.
- HIV-1 genetic diversity and transmitted drug resistance in health care settings in Maputo, MozambiquePublication . Bártolo, Inês; Casanovas, José; Bastos, Rui; Rocha, Cheila; Abecasis, Ana B.; Folgosa, Elena; Mondlane, José; Manuel, Rolanda; Taveira, NunoObjectives: To characterize HIV-1 diversity and transmitted drug resistance in persons with access to care and treatment in Maputo, Mozambique. Methods: Samples were collected in 2002-2004 from 144 drug-naive patients attending public hospitals and private clinics. Plasma viremia, CD4, and CD8 cell counts were determined for each patient. The Stanford Algorithm was used for resistance genotyping on pol sequences. Subtyping was done by phylogenetic analysis. Results: Most patients had high viral load (mean, 5.0 log copies/mL) and low CD4 cell counts (median, 260 CD4 cells/μL). Protease and/or reverse transcriptase sequences were obtained from 104 (72%) samples. Patients harbored subtypes C (80.8%), G (3.8%), CRF37_cpx (6.7%), untypable (U) (1.0%), and recombinant strains (7.7%) comprising the A, C, D, F, and U clades. There were no major protease inhibitor resistance mutations. Mutations conferring resistance to the nucleoside/nucleotide reverse transcriptase inhibitors and/or nonnucleoside reverse transcriptase inhibitors were found in 4 (4/68; 5.9%) patients. Phylogenetic analysis suggested an imported origin for 2 resistant variants. Conclusions: The HIV-1 epidemic in Maputo is evolving rapidly in genetic complexity due to the recent introduction of all major subtypes and recombinant forms. Continued surveillance of drug resistance in treated and untreated populations is needed to prevent further transmission of HIV drug-resistant variants and maximize the efficacy of antiretroviral therapy in Maputo.
- Rapid clinical progression to AIDS and death in a persistently seronegative HIV-1 infected heterosexual young manPublication . Bártolo, Inês; Camacho, Ricardo; Barroso, Helena; Bezerra, Victor; Taveira, NunoSeronegative HIV-1 infection has important implications for diagnosis and prevention. We describe a case of HIV-1 infection without seroconversion and fast progression to AIDS and death. Genetic and phylogenetic analysis indicated that the patient was infected with a CRF14_BG-like strain selectively transmitted by his seropositive sexual partner. The results suggest a massive infection with a highly aggressive CRF14_BG-like strain and/or the presence of an unidentified immunological deficiency that has prevented the formation of HIV-1-specific antibodies.
- Highly divergent subtypes and new recombinant forms prevail in the HIV/AIDS epidemic in Angola: New insights into the origins of the AIDS pandemicPublication . Bártolo, Inês; Rocha, Cheila; Bartolomeu, José; Gama, António; Marcelino, Rute; Fonseca, Marlene; Mendes, Ana; Epalanga, Marta; Silva, Patrícia Cavaco; Taveira, NunoAngola, located in South-Western Africa, has a remarkably low HIV/AIDS prevalence in the adult population (3.7%). It is bordered in the North by the Democratic Republic of Congo (DRC) and Republic of Congo that are at the origin of human HIV-1 infections. It is, therefore, likely that HIV-1 strains circulating in Angola are genetically diverse and representative of the origin of the HIV/AIDS epidemic. The aim of this work was to investigate in detail the genetic diversity and molecular epidemiology of HIV-1 in Angola. Almost 400 sequences were obtained from the gag (p17), pol (PR and RT) and/or env (C2C3) genes of 159 HIV-1 infected patients living in eight provinces of Angola (Benguela, Cabinda, Cuanza Norte, Luanda, Lunda Norte, Malange, Uíge, and Zaire) and their genotype was determined by phylogenetic analyses. Gene regions representing all HIV-1 group M clades were found as well as unclassifiable sequences. In env and pol (RT), two groups of sequences forming distinct sub-clusters within the subtype A radiation were found and may define new A5 and A6 sub-subtypes. Recombinant forms were found in almost half (47.1%) of the patients of which 36.0% were second-generation recombinants. Fifty-eight different patterns of recombination were found. The A subtype, including CRF02_AG, was represented in most recombinant viruses. Epidemiological data suggests that the AIDS epidemic in Angola has probably started as early as 1961, the major cause being the independence war, and spread to Portugal soon thereafter. The extraordinary degree of HIV-1 group M genetic diversity and evolution in Angola may pose unprecedented challenges to diagnostic, treatment and prevention of HIV-1 infection.
- Evolutionary and structural features of the C2, V3 and C3 envelope regions underlying the differences in HIV-1 and HIV-2 biology and infectionPublication . Barroso, Helena; Borrego, Pedro; Bártolo, Inês; Marcelino, José Maria; Familia, Carlos; Quintas, Alexandre; Taveira, NunoBackground Unlike in HIV-1 infection, the majority of HIV-2 patients produce broadly reactive neutralizing antibodies, control viral replication and survive as elite controllers. The identification of the molecular, structural and evolutionary footprints underlying these very distinct immunological and clinical outcomes may lead to the development of new strategies for the prevention and treatment of HIV infection. Methodology/Principal Findings We performed a side-by-side molecular, evolutionary and structural comparison of the C2, V3 and C3 envelope regions from HIV-1 and HIV-2. These regions contain major antigenic targets and are important for receptor binding. In HIV-2, these regions also have immune modulatory properties. We found that these regions are significantly more variable in HIV-1 than in HIV-2. Within each virus, C3 is the most entropic region followed by either C2 (HIV-2) or V3 (HIV-1). The C3 region is well exposed in the HIV-2 envelope and is under strong diversifying selection suggesting that, like in HIV-1, it may harbour neutralizing epitopes. Notably, however, extreme diversification of C2 and C3 seems to be deleterious for HIV-2 and prevent its transmission. Computer modelling simulations showed that in HIV-2 the V3 loop is much less exposed than C2 and C3 and has a retractile conformation due to a physical interaction with both C2 and C3. The concealed and conserved nature of V3 in the HIV-2 is consistent with its lack of immunodominancy in vivo and with its role in preventing immune activation. In contrast, HIV-1 had an extended and accessible V3 loop that is consistent with its immunodominant and neutralizing nature. Conclusions/Significance We identify significant structural and functional constrains to the diversification and evolution of C2, V3 and C3 in the HIV-2 envelope but not in HIV-1. These studies highlight fundamental differences in the biology and infection of HIV-1 and HIV-2 and in their mode of interaction with the human immune system and may inform new vaccine and therapeutic interventions against these viruses.