ALVINA CLARA FELIX
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
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- A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus(2017) MAGNANI, Diogo M.; SILVEIRA, Cassia G. T.; ROSEN, Brandon C.; RICCIARDI, Michael J.; PEDRENO-LOPEZ, Nuria; GUTMAN, Martin J.; BAILEY, Varian K.; MAXWELL, Helen S.; DOMINGUES, Aline; GONZALEZ-NIETO, Lucas; AVELINO-SILVA, Vivian I.; TRINDADE, Mateus; NOGUEIRA, Juliana; OLIVEIRA, Consuelo S.; MAESTRI, Alvino; FELIX, Alvina Clara; LEVI, Jose Eduardo; NOGUEIRA, Mauricio L.; MARTINS, Mauricio A.; MARTINEZ-NAVIO, Jose M.; FUCHS, Sebastian P.; WHITEHEAD, Stephen S.; BURTON, Dennis R.; DESROSIERS, Ronald C.; KALLAS, Esper G.; WATKINS, David I.The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut(50) similar to 2 mu g/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.
- MAIT cells are activated in acute Dengue virus infection and after in vitro Zika virus infection(2018) PAQUIN-PROULX, Dominic; AVELINO-SILVA, Vivian I.; SANTOS, Bianca A. N.; BARSOTTI, Nathalia Silveira; SIROMA, Fabiana; RAMOS, Jessica Fernandes; TONACIO, Adriana Coracini; SONG, Alice; MAESTRI, Alvino; CERQUEIRA, Natalia Barros; FELIX, Alvina Clara; LEVI, Jose Eduardo; GREENSPUN, Benjamin C.; ROUGVIE, Miguel de Mulder; ROSENBERG, Michael G.; NIXON, Douglas F.; KALLAS, Esper G.Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are pre-dominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barre A syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFN gamma response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFN gamma in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.
- Enhanced detection of viral diversity using partial and near full-length genomes of human immunodeficiency virus Type 1 provirus deep sequencing data from recently infected donors at four blood centers in Brazil(2015) PESSOA, Rodrigo; WATANABE, Jaqueline Tomoko; CALABRIA, Paula; ALENCAR, Cecilia Salete; LOUREIRO, Paula; LOPES, Maria Esther; PROETTI, Anna Barbara; FELIX, Alvina Clara; SABINO, Ester C.; BUSCH, Michael P.; SANABANI, Sabri S.BackgroundHere, we report application of high-throughput near full-length genome (NFLG) and partial human immunodeficiency virus Type 1 (HIV-1) proviral genome deep sequencing to characterize HIV in recently infected blood donors at four major blood centers in Brazil. Study Design and MethodsFrom 2007 to 2011, a total of 341 HIV+ blood donors from four blood centers were recruited to participate in a case-control study to identify HIV risk factors and motivations to donate. Forty-seven (17 from SAo Paulo, eight from Minas Gerais, 11 from Pernambuco, and 11 from Rio de Janeiro) were classified as recently infected based on testing by less-sensitive enzyme immunoassays. Five overlapping amplicons spanning the HIV genome were polymerase chain reaction amplified from peripheral blood mononuclear cells. The amplicons were molecularly barcoded, pooled, and sequenced by a paired-end protocol (Illumina). ResultsOf the 47 recently infected donor samples studied, 39 (82.9%) NFLGs and six (12.7%) partial fragments were de novo assembled into contiguous sequences and successfully subtyped. Subtype B was the only nonrecombinant virus identified in this study and accounted for 62.2% (28/45) of samples. The remaining 37.8% (17/45) of samples showed various patterns of subtype discordance in different regions of HIV-1 genomes, indicating two to four circulating recombinant subtypes derived from Clades B, F, and C. Fourteen samples (31.1%) from this study harbored drug resistance mutations, indicating higher rate of drug resistance among Brazilian blood donors. ConclusionOur findings revealed a high proportion of HIV-1 recombinants among recently infected blood donors in Brazil, which has implications for future blood screening, diagnosis, therapy, and vaccine development.
- Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing(2023) CLARO, I. M.; RAMUNDO, M. S.; COLETTI, T. M.; SILVA, C. A. M. da; VALENCA, I. N.; CANDIDO, D. S.; SALES, F. C. S.; MANULI, E. R.; JESUS, J. G. de; PAULA, A. de; FELIX, A. C.; ANDRADE, P. D. S.; PINHO, M. C.; SOUZA, W. M.; AMORIM, M. R.; PROENCA-MODENA, J. L.; KALLAS, E. G.; LEVI, J. E.; FARIA, N. R.; SABINO, E. C.; LOMAN, N. J.; QUICK, J.Emerging and re-emerging viruses are a global health concern. Genome sequencing as an approach for monitoring circulating viruses is currently hampered by complex and expensive methods. Untargeted, metagenomic nanopore sequencing can provide genomic information to identify pathogens, prepare for or even prevent outbreaks. SMART (Switching Mechanism at the 5′ end of RNA Template) is a popular approach for RNA-Seq but most current methods rely on oligo-dT priming to target polyadenylated mRNA molecules. We have developed two random primed SMART-Seq approaches, a sequencing agnostic approach ‘SMART-9N’ and a version compatible rapid adapters available from Oxford Nanopore Technologies ‘Rapid SMART-9N’. The methods were developed using viral isolates, clinical samples, and compared to a gold-standard amplicon-based method. From a Zika virus isolate the SMART-9N approach recovered 10kb of the 10.8kb RNA genome in a single nanopore read. We also obtained full genome coverage at a high depth coverage using the Rapid SMART-9N, which takes only 10 minutes and costs up to 45% less than other methods. We found the limits of detection of these methods to be 6 focus forming units (FFU)/mL with 99.02% and 87.58% genome coverage for SMART-9N and Rapid SMART-9N respectively. Yellow fever virus plasma samples and SARS-CoV-2 nasopharyngeal samples previously confirmed by RT-qPCR with a broad range of Ct-values were selected for validation. Both methods produced greater genome coverage when compared to the multiplex PCR approach and we obtained the longest single read of this study (18.5 kb) with a SARS-CoV-2 clinical sample, 60% of the virus genome using the Rapid SMART-9N method. This work demonstrates that SMART-9N and Rapid SMART-9N are sensitive, low input, and long-read compatible alternatives for RNA virus detection and genome sequencing and Rapid SMART-9N improves the cost, time, and complexity of laboratory work.