Browsing by Author "Barroso, Helena"
Now showing 1 - 10 of 19
Results Per Page
Sort Options
- An ancestral HIV-2/simian immunodeficiency virus peptide with potent HIV-1 and HIV-2 fusion inhibitor activityPublication . Borrego, Pedro; Calado, Rita; Marcelino, José M.; Pereira, Patrícia; Quintas, Alexandre; Barroso, Helena; Taveira, Nuno"Objectives: To produce new fusion inhibitor peptides for HIV-1 and HIV-2 based on ancestral envelope sequences. Methods: HIV-2/simian immunodeficiency virus (SIV) ancestral transmembrane protein sequences were reconstructed and ancestral peptides were derived from the helical region 2 (HR2). The activity of one ancestral peptide (named P3) was examined against a panel of HIV-1 and HIV-2 primary isolates in TZM-bl cells and peripheral blood mononuclear cells and compared to T-20. Peptide secondary structure was analyzed by circular dichroism. Resistant viruses were selected and resistance mutations were identified by sequencing the env gene. Results: P3 has 34 residues and overlaps the N-terminal pocket-binding region and heptad repeat core of HR2. In contrast to T-20, P3 forms a typical a-helical structure in solution, binds strongly to the transmembrane protein, and potently inhibits both HIV-2 (mean IC50, 63.8 nmol/l) and HIV-1 (11 nmol/l) infection, including T-20-resistant isolates. The N43K mutation in the HR1 region of HIV-1 leads to 120-fold resistance to P3 indicating that the HR1 region in transmembrane glycoprotein is the target of P3. No HIV-2-resistant mutations could be selected by P3 suggesting that the genetic barrier to resistance is higher in HIV-2 than in HIV-1. HIV-1-infected patients presented significantly lower P3-specific antibody reactivity compared to T-20. Conclusion: P3 is an HIV-2/SIV ancestral peptide with low antigenicity, high stability, and potent activity against both HIV-1, including variants resistant to T-20, and HIV-2. Similar evolutionary biology strategies should be explored to enhance the production of antiviral peptide drugs, microbicides, and vaccines."
- Baseline susceptibility of primary HIV-2 to entry inhibitorsPublication . Borrego, Pedro; Calado, Rita; Marcelino, José M; Bártolo, Inês; Rocha, Cheila; Cavaco-Silva, Patrícia; Doroana, Manuela; Antunes, Francisco; Maltez, Fernando; Caixas, Umbelina; Barroso, Helena; Taveira, NunoBackground: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown.
- Beach sand and the potential for infectious disease transmission: observations and recommendationsPublication . Solo-Gabriele, Helena M.; Harwood, Valerie J.; Kay, David; Fujioka, Roger S.; Sadowsky, Michael J.; Whitman, Richard L.; Wither, Andrew; Caniça, Manuela; Fonseca, Rita Carvalho da; Duarte, Aida; Edge, Thomas A.; Gargaté, Maria J.; Gunde-Cimerman, Nina; Hagen, Ferry; McLellan, Sandra L.; Silva, Alexandra Nogueira da; Babič, Monika Novak; Prada, Susana; Rodrigues, Raquel; Romão, Daniela; Sabino, Raquel; Samson, Robert A.; Segal, Esther; Staley, Christopher; Taylor, Huw D.; Veríssimo, Cristina; Viegas, Carla; Barroso, Helena; Brandão, João C."Recent studies suggest that sand can serve as a vehicle for exposure of humans to pathogens at beach sites, resulting in increased health risks. Sampling for microorganisms in sand should therefore be considered for inclusion in regulatory programmes aimed at protecting recreational beach users from infectious disease. Here, we review the literature on pathogen levels in beach sand, and their potential for affecting human health. In an effort to provide specific recommendations for sand sampling programmes, we outline published guidelines for beach monitoring programmes, which are currently focused exclusively on measuring microbial levels in water. We also provide background on spatial distribution and temporal characteristics of microbes in sand, as these factors influence sampling programmes. First steps toward establishing a sand sampling programme include identifying appropriate beach sites and use of initial sanitary assessments to refine site selection. A tiered approach is recommended for monitoring. This approach would include the analysis of samples from many sites for faecal indicator organisms and other conventional analytes, while testing for specific pathogens and unconventional indicators is reserved for high-risk sites. Given the diversity of microbes found in sand, studies are urgently needed to identify the most significant aetiological agent of disease and to relate microbial measurements in sand to human health risk."
- Candida spp. colonization among intensive care unit patients : preliminary resultsPublication . Nascimento, Teresa; Inácio, João; Ferreira, Isabel; Diaz, Priscila; Freitas, Paulo; Barroso, HelenaCandida spp. colonization is recognized as a major risk factor for invasive candidiasis. To assess patient colonization, upon admission and during their stay in intensive care units (ICU), a surveillance study has been conducted since January 2020, in the Lisbon area of Portugal. A total of 219 swab samples were obtained from 113 ICU patients. The yeast identification was conducted by microbiological conventional and molecular methods. Upon admission to the ICU, 27% of patients were already colonized, and 17% became colonized during their ICU stay. Candida albicans was the most isolated species. These results may offer an opportunity for prevention of candidemia.
- Children and sand play: screening of potential harmful microorganisms in sandboxes, parks, and beachesPublication . Romão, Daniela; Sabino, Raquel; Veríssimo, Cristina; Viegas, Carla; Barroso, Helena; Duarte, Aida; Solo-Gabriele, Helena; Gunde-Cimerman, Nina; Babič, Monika Novak; Marom, Tal; Brandão, JoãoSand serves as a reservoir for potentially pathogenic microorganisms. Children, a high-risk group, can acquire infections from sand in sandboxes, recreational areas, and beaches. This paper reviews the microbes in sands, with an emphasis on fungi. Recreational areas and beach sands have been found to harbor many types of fungi and microbes. A newly emerging group of fungi of concern include the black yeast-like fungi. After establishing that sand is a reservoir for fungi, clinical manifestations of fungal infections are described with an emphasis on ocular and ear infections. Overall, we recommend environmental studies to develop monitoring strategies for sand and studies to evaluate the link between fungi exposure in sand and human health impacts.
- Estudo da contaminação microbiana em cones de gutta-perchaPublication . Baio, Elisa; Barroso, Helena; Azul, Ana Cristina; Proença, Luís; Mendes, José João
- Evaluation of antifungal susceptibility in clinical isolates of the Candida glabrata complexPublication . Jesus, Filipa; Barroso, Helena; Nascimento, Teresa
- Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in womenPublication . Bártolo, Inês; Diniz, Ana Rita; Borrego, Pedro; Ferreira, João Pedro; Bronze, Maria Rosário; Barroso, Helena; Pinto, Rui; Cardoso, Carlos; Pinto, João F.; Diaz, Rafael Ceña; Broncano, Pilar Garcia; Muñoz-Fernández, Maria Angel; Taveira, NunoMicrobicides are an important strategy for preventing the sexual transmission of HIV but, so far, the most advanced tenofovir-based microbicides have had modest efficacy. This has been related to adherence problems and high prevalence of tenofovir-resistant HIV-1 strains. P3 is a new peptide with potent activity against HIV that may be a good microbicide candidate. In this work P3 was formulated in a gel of hydroxyethyl cellulose and its activity, stability and safety profile in Balb/c mice were evaluated. HIV infection was fully blocked by a 1.5% gel containing P3 at the IC90 (366.4 nM) concentration. The antiviral activity did not change at 4°C during 4 months and at 25, 37 and 65°C for 1 week. P3 was stable and fully functional at acidic pH up to 24h, under different concentrations of hydrogen peroxide and in the presence of genital fluids up to 48h. P3 had no antibacterial activity and did not affect sperm motility and vitality. Finally, P3 didn't cause significant alterations in the vaginal epithelium of Balb/c mice at 0.06 (456.8 μM) and 0.2 mg/day (1522.7 μM) doses. These findings indicate that P3 is an excellent candidate for further development as a microbicide gel for the prevention of HIV transmission in women.
- Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody responsePublication . Rocha, Cheila; Calado, Rita; Borrego, Pedro; Marcelino, José Maria; Bártolo, Inês; Rosado, Lino; Cavaco-Silva, Patrícia; Perpétua, Gomes; Família, Carlos; Quintas, Alexandre; Skar, Helena; Leitner, Thomas; Barroso, Helena; Taveira, Nuno"Background: Differently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth. Results: CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Conclusion: Our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis."
- 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; Família, 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.