Biology subjects

Delatorre, E.

Publications and source records attributed to Delatorre, E..

6 recordsLinked to original sources

bioRxiv2021

A potential SARS-CoV-2 variant of interest (VOI) harboring mutation E484K in the Spike protein was identified within lineage B.1.1.33 circulating in Brazil

The SARS-CoV-2 epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. Two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved within lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North and Northeast regions.

microbiology↗

bioRxiv2020

Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil

Despite all efforts to control the COVID-19 spread, the SARS-CoV-2 reached South America within three months after its first detection in China, and Brazil became one of the hotspots of COVID-19 in the world. Several SARS-CoV-2 lineages have been identified and some local clusters have been described in this early pandemic phase in Western countries. Here we investigated the genetic diversity of SARS-CoV-2 during the early phase (late February to late April) of the epidemic in Brazil. Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. This SARS-CoV-2 Brazilian lineage was probably established during February 2020 and rapidly spread through the country, reaching different Brazilian regions by the middle of March 2020. Our study also supports occasional exportations of this Brazilian B.1.1 lineage to neighboring South American countries and to more distant countries before the implementation of international air travels restrictions in Brazil.

evolutionary biology↗

bioRxiv2019

HIV-1 controllers exhibit an enhanced antiviral state characterized by overexpression of p21 and MCPIP1

Some multifunctional cellular proteins, as the monocyte chemotactic protein-induced protein 1 (MCPIP1) and the cyclin-dependent kinase inhibitor p21, have also shown to be able to modulate the cellular susceptibility to the human immunodeficiency virus type 1 (HIV-1). Several studies described that p21 is expressed at high levels ex vivo in cells from individuals who naturally control HIV-1 replication (HIC). The expression level of MCPIP1 in HIC was never described before, but a recent study in a model of renal carcinoma cells showed that MCPIP1 overexpression was associated with an increase of both p21 transcripts and proteins levels. Here, we explored the potential associations between MCPIP1 and p21 expression, as well as with cellular activation in HIC, sustaining undetectable (elite controllers - EC) or low (viremic controllers - VC) viral loads. We found a selective upregulation of MCPIP1 and p21 mRNA levels in PBMC from HIC compared with both ART- suppressed and HIV-negative control groups (P [≤] 0.02) and a strong positive correlation (r [≥] 0.57; P [≤] 0.014) between expressions of both transcripts independently of the VL, treatment condition and HIV status. The mRNA levels of p21, but not of MCPIP1, were positively correlated with activated CD4+ T cells levels in HIC and EC (r [≥] 0.53; P [≤] 0.017). In relation to the monocyte activation, the mRNA levels of both p21 (r = 0.74; P = 0.005) and MCPIP1 (r = 0.58; P = 0.040) were positively correlated with plasmatic levels of sCD14 only in EC. Multivariate analysis confirmed the association between MCPIP1 and p21 mRNA levels, and between the latter with the frequency of activated CD4+ T cells. These data show for the first time the simultaneous overexpression and positive correlation of MCPIP1 and p21 transcripts in the setting of natural suppression of HIV-1 replication in vivo. The positive correlation between MCPIP1 and p21 transcripts supports a common regulatory pathway connecting these multifunctional host factors and a possible synergistic effect on HIV-1 replication control. Pharmacological manipulation of these cellular proteins may open novel therapeutic perspectives to prevent HIV-1 replication and disease progression.

immunology↗

bioRxiv2019

Distinct YFV lineages co-circulated in the Central-Western and Southeastern Brazilian regions from 2015 to 2018

The current outbreak of yellow fever virus (YFV) that is afflicting Brazil since the end of 2016 probably originated from a re-introduction of YFV from endemic areas into the non-endemic Southeastern Brazil. However, the lack of genomic sequences from endemic regions hinders the tracking of YFVs dissemination routes. We assessed the origin and spread of the ongoing YFV Brazilian outbreak analyzing a new set of YFV strains infecting humans, non-human primates (NHP) and mosquitoes sampled across five Brazilian states from endemic and non-endemic regions between 2015 and 2018. We found two YFV sub-clade 1E lineages circulating in NHP from Goias state (GO), resulting from independent viral introductions into the Araguaia tributary river basin: while the strain from 2017 clustered intermingled with Venezuelan YFV strains from 2000, the YFV strain sampled in 2015 clustered with sequences of the current YFV outbreak in the Brazilian Southeastern region (named YFV2015-2018 lineage), displaying the same molecular signature associated to the current YFV outbreak. After its introduction in GO at around mid-2014, the YFV2015-2018 lineage followed two paths of dissemination outside GO, originating two major YFV sub-lineages: 1) the YFVMG/ES/RJ sub-lineage spread sequentially from the eastern area of Minas Gerais state to Espirito Santo and then to Rio de Janeiro states, following the Southeast Atlantic basin; 2) the YFVMG/SP sub-lineage spread from the southwestern area of Minas Gerais to the metropolitan region of Sao Paulo state, following the Parana basin. These results indicate the ongoing YFV outbreak in Southeastern Brazil originated from a dissemination event from GO almost two years before its recognition at the end of 2016. From GO this lineage was introduced in Minas Gerais state at least two times, originating two sub-lineages that followed different routes towards densely populated areas. The spread of YFV outside endemic regions for at least four years stresses the imperative importance of the continuous monitoring of YFV to aid decision-making for effective control policies aiming the increase of vaccination coverage to avoid the YFV transmission in densely populated urban centers.

epidemiology↗

bioRxiv2018

Emergence of the East-Central-South-African genotype of Chikungunya virus in Brazil and the city of Rio de Janeiro may have occurred years before surveillance detection

Brazil, which is hyperendemic for dengue virus (DENV), has had recent Zika (ZIKV) and (CHIKV) Chikungunya virus outbreaks. Since March 2016, CHIKV is the arbovirus infection most frequently diagnosed in Rio de Janeiro. In the analysis of 1835 syndromic patients, screened by real time RT-PCR, 56.4% of the cases were attributed to CHIKV, 29.6% to ZIKV, and 14.1% to DENV-4. Sequence analyses of CHIKV from sixteen samples revealed that the East-Central-South-African (ECSA) genotype of CHIKV has been circulating in Brazil since 2013 [95% bayesian credible interval (BCI): 03/2012-10/2013], almost a year before it was detected by arbovirus surveillance program. Brazilian cases are related to Central African Republic sequences from 1980s. To the best of our knowledge, given the available sequence published here and elsewhere, the ECSA genotype was likely introduced to Rio de Janeiro early on 2014 (02/2014; BCI: 07/2013-08/2014) through a single event, after primary circulation in the Bahia state at the Northestern Brazil in the previous year. The observation that the ECSA genotype of CHIKV was circulating undetected underscores the need for improvements in molecular methods for viral surveillance.

genomics↗

bioRxiv2017

Genome sequencing reveals Zika virus diversity and spread in the Americas

Despite great attention given to the recent Zika virus (ZIKV) epidemic in the Americas, much remains unknown about its epidemiology and evolution, in part due to a lack of genomic data. We applied multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analyzed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental US. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of viral surveillance. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those potentially relevant to the effectiveness of diagnostic tests.

genomics↗