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
3 resultados
Resultados de Busca
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- Dengue Virus Serotype 2 Intrahost Diversity in Patients with Different Clinical Outcomes(2021) TORRES, Maria Celeste; MENDONCA, Marcos Cesar Lima de; RODRIGUES, Cintia Damasceno dos Santos; FONSECA, Vagner; RIBEIRO, Mario Sergio; BRANDAO, Ana Paula; CUNHA, Rivaldo Venancio da; DIAS, Ana Isabel; BOAS, Lucy Santos Vilas; FELIX, Alvina Clara; PEREIRA, Maira Alves; PINTO, Luzia Maria de Oliveira; SAKUNTABHAI, Anavaj; FILIPPIS, Ana Maria Bispo deIntrahost genetic diversity is thought to facilitate arbovirus adaptation to changing environments and hosts, and it might also be linked to viral pathogenesis. Dengue virus serotype 2 (DENV-2) has circulated in Brazil since 1990 and is associated with severe disease and explosive outbreaks. Intending to shed light on the viral determinants for severe dengue pathogenesis, we sought to analyze the DENV-2 intrahost genetic diversity in 68 patient cases clinically classified as dengue fever (n = 31), dengue with warning signs (n = 19), and severe dengue (n = 18). Unlike previous DENV intrahost diversity studies whose approaches employed PCR, here we performed viral whole-genome deep sequencing from clinical samples with an amplicon-free approach, representing the real intrahost diversity scenario. Striking differences were detected in the viral population structure between the three clinical categories, which appear to be driven mainly by different infection times and selection pressures, rather than being linked with the clinical outcome itself. Diversity in the NS2B gene, however, showed to be constrained, irrespective of clinical outcome and infection time. Finally, 385 non-synonymous intrahost single-nucleotide variants located along the viral polyprotein, plus variants located in the untranslated regions, were consistently identified among the samples. Of them, 124 were exclusively or highly detected among cases with warning signs and among severe cases. However, there was no variant that by itself appeared to characterize the cases of greater severity, either due to its low intrahost frequency or the conservative effect on amino acid substitution. Although further studies are necessary to determine their real effect on viral proteins, this heightens the possibility of epistatic interactions. The present analysis represents an initial effort to correlate DENV-2 genetic diversity to its pathogenic potential and thus contribute to understanding the virus's dynamics within its human host.
- Phylogenetics, Epidemiology and Temporal Patterns of Dengue Virus in Araraquara, São Paulo State(2024) SOUZA, Caio Santos de; CALEIRO, Giovana Santos; CLARO, Ingra Morales; JESUS, Jaqueline Goes de; COLETTI, Thais Moura; SILVA, Camila Alves Maia da; COSTA, Angela Aparecida; INENAMI, Marta; RIBEIRO, Andreia C.; FELIX, Alvina Clara; PAULA, Anderson Vicente de; FIGUEIREDO, Walter M.; LUNA, Expedito Jose de Albuquerque; SABINO, Ester C.; ROMANO, Camila M.Dengue virus (DENV) is a prominent arbovirus with global spread, causing approximately 390 million infections each year. In Brazil, yearly epidemics follow a well-documented pattern of serotype replacement every three to four years on average. Araraquara, located in the state of Sao Paulo, has faced significant impacts from DENV epidemics since the emergence of DENV-1 in 2010. The municipality then transitioned from low to moderate endemicity in less than 10 years. Yet, there remains an insufficient understanding of virus circulation dynamics, particularly concerning DENV-1, in the region, as well as the genetic characteristics of the virus. To address this, we sequenced 37 complete or partial DENV-1 genomes sampled from 2015 to 2022 in Araraquara. Then, using also Brazilian and worldwide DENV-1 sequences we reconstructed the evolutionary history of DENV-1 in Araraquara and estimated the time to the most recent common ancestor (tMRCA) for serotype 1, for genotype V and its main lineages. Within the last ten years, there have been at least three introductions of genotype V in Araraquara, distributed in two main lineages (L Ia and L Ib, and L II). The tMRCA for the first sampled lineage (2015/2016 epidemics) was approximately 15 years ago (in 2008). Crucially, our analysis challenges existing assumptions regarding the emergence time of the DENV-1 genotypes, suggesting that genotype V might have diverged more recently than previously described. The presence of the two lineages of genotype V in the municipality might have contributed to the extended persistence of DENV-1 in the region.
- Plaque Reduction Neutralization Test (PRNT) in the Congenital Zika Syndrome: Positivity and Associations with Laboratory, Clinical, and Imaging Characteristics(2020) RIBEIRO, Marizelia R. C.; KHOURI, Ricardo; SOUSA, Patricia S.; BRANCO, Maria R. F. C.; BATISTA, Rosangela F. L.; COSTA, Elaine P. F.; ALVES, Maria T. S. S. B.; AMARAL, Glaucio A.; BORGES, Marcella C. R.; TAKAHASI, Eliana H. M.; GOMES, Lillian N.; MENDES, Ana K. T.; CAVALCANTE, Tamires B.; COSTA, Luciana C.; FELIX, Alvina C.; SOUZA, Nathalia C. S.; SILVA, Antonio A. M.The short duration of viremia, low blood viral load, inaccessibility to timely specific diagnostic tests, and cross-reactions with other flaviviruses have hindered laboratory confirmation of Congenital Zika Syndrome (CZS). This study analyzes the positivity of the plaque reduction neutralization test (PRNT) in children with clinical or imaging characteristics of CZS and its association with laboratory, clinical, and imaging characteristics. The 94 clinical cases of CZS submitted to the ZIKV PRNT90 test were followed from 2016 to 2018. The mean age of children at PRNT90 collection was 22 +/- 6 months Standard Deviation. The ZIKV PRNT90 was positive (titer >= 10) in 40 (42.5%) children. ZIKV PRNT90 positivity was associated with severe microcephaly in newborns (p = 0.016), lower head circumference z-score at birth (p = 0.043) and 24 months of age (p = 0.031), and severe reduction of the cerebral parenchyma volume (p = 0.021), expressing greater disease severity. Negative PRNT90 in children with characteristic signs of CZS may be due to false-negative results, indicating that the diagnosis of CZS should be primarily syndromic.