Biology subjects

Oliveira, L. G.

Publications and source records attributed to Oliveira, L. G..

3 recordsLinked to original sources

bioRxiv2021

Zika Virus Infection of Murine and Human Neutrophils and their Function as Trojan Horses to the Placenta

ZIKV is a 11Kb positive stranded flavivirus transmitted by infected Aedes aegypti and by sexual intercourse. After a short period of viremia of 5-7 days, the virus is cleared, and infection resolved in 80% of individuals. However, around 27% of the fetuses from pregnant infected mothers may develop several fetal brain and ocular pathology. Here we show that murine and peripheral blood human neutrophils support ZIKV infection and replication both in vitro and in vivo, which may correlate to the facilitation of vertical transmission. ZIKV did not interfere with cell viability, neither induced ROS production nor the release of NETs by infected neutrophils. Also, ZIKV infection of neutrophils did not trigger a pro-inflammatory profile, as evidenced by qPCR and proteomic analysis. Interestingly, ZIKV-infected neutrophils were isolated from the placenta were highly infected. The transference of in vitro ZIKV-infected neutrophils to pregnant female mice favored the transference of viral particles to the fetus. Conversely, neutrophil depletion with monoclonal antibodies reduced fetal viral loads whereas the treatment with recombinant G-CSF has the opposite effect. In summary, although it has already been shown that circulating monocytes harbor ZIKV, to our knowledge, this is the first report demonstrating the role of neutrophils during ZIKV infection, and most important, that it may act as a trojan horse to placental tissue directly impacting the pathogenesis of congenital syndrome.

immunology↗

bioRxiv2021

Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations remain unknown. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate high Gas6 levels in the serum of patients with neurological complications which correlated with downregulation of genes associated with the type I IFN responses as consequence of Socs1 upregulation. Gas6 gamma-carboxylation is essential for ZIKV replication in monocytes, the main source of this protein. Gas6 also facilitates ZIKV replication in adult immunocompetent mice enabled susceptibility to transplacental infection and congenital malformations. Our data thus indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

microbiology↗

bioRxiv2020

Deviation from mendelian transmission of autosomal SNPs can be used to estimate germline mutations in humans exposed to ionizing radiation

We aimed to estimate the rate of germline mutations in the offspring of individuals accidentally exposed to Cesium-137 ionizing radiation. Performed analysis considered two distinct groups: a group males and females accidentally exposed to low doses of ionizing radiation from Cs137, the case group, and a control group of non-exposed participants. The case group included 37 participants (11 couples and 15 children born after the accident). The dose absorbed by exposed participants ranged from 0.2 to 0.5 Gray. The control group included 15 families from the state of Goias, with no history of radiation exposure. DNA samples from peripheral blood were analyzed with the Affymetrix GeneChip(R) CytoScanHD to assess de novo SNP-type mutations. A set of scripts previously developed was used to detect de novo mutations by comparing parent and offspring genotypes in each SNP marker. Overall numbers of observed Mendelian deviations were statistically significant between the exposed and control groups. Offspring from the population accidentally exposed to low IR doses showed [~] 46.5% more de novo Mendelian deviations than the control group. Parent-of-origin and type of nucleotide substitution were also inferred. Estimates of age-adjusted de novo germline mutation rates were obtained and correlated to Cs-137 radiation dose exposure to evaluate the usefulness of the rate of Mendelian deviations observed in polymorphic SNPs as a biomarker for exposure. This proved useful in a retrospective estimation of the rate of de novo germline mutations in a human population accidentally exposed to low doses of radiation from Cs-137. Obtained results suggest that observed burden of germline mutations identified in offspring could potentially be a useful biomarker to estimate levels of parental exposure to ionizing radiation.

genetics↗