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Biomedical subjects

Fernanda Sales Luiz Vianna

Publications and source records attributed to Fernanda Sales Luiz Vianna.

2 recordsLinked to original sources

Oropouche virus infection: clinical spectrum, geographic expansion, and emerging maternal-fetal implications.

Oropouche virus (OROV), an emerging arbovirus of the genus Orthobunyavirus, has become a growing public health concern following its recent expansion across the Americas and its potential to cause severe clinical outcomes in maternal and child health. Although Oropouche fever has classically been described as an acute self-limited febrile illness, accumulating evidence indicates that OROV is associated with meningitis and fatal infection, as well as evidence of vertical transmission associated with adverse fetal outcomes, including microcephaly and other congenital abnormalities, spontaneous abortion, stillbirth, and neuropathological alterations resembling those observed in congenital Zika syndrome. The OROV presents two transmission cycles, namely sylvatic and urban, with Culicoides paraensis as its main vector. The absence of specific vaccines or treatments, together with the wide distribution of competent vectors and the possibility of sexual transmission, underscores the urgent need to strengthen epidemiological surveillance, elucidate the mechanisms of fetal pathogenesis, and develop effective prevention and control strategies to protect vulnerable populations.

Orthobunyavirus

Defective RNA Polymerase III sensing of mitochondrial DNA in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2.

The clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection ranges from asymptomatic cases to critical COVID-19 pneumonia. To investigate the role of host genetics in susceptibility to critical COVID-19 and identify pathophysiological mechanisms and pathways, we analyzed whole-exome and whole-genome sequencing data from the COVID Human Genetic Effort. We identified 10 rare, monoallelic predicted loss-of-function variants in 18 patients in POLR3A and POLR3C encoding two subunits of RNA polymerase III (POL III), a nuclear multisubunit enzyme, which has been implicated in cytosolic DNA sensing. These variants were deleterious for expression of full-length POLR3A and POLR3C proteins. We demonstrate that human pulmonary A549-hACE2 cells with reduced POLR3A or POLR3C expression exhibit impaired type I IFN responses to transfected mitochondrial DNA (mtDNA) or SARS-CoV-2 infection, together with increased viral replication. Mechanistically, we show that SARS-CoV-2 induces cellular mtDNA release via oligomerization of the mitochondrial voltage-dependent anion channel under virus-induced oxidative stress, enabling POL III-mtDNA interaction. These findings establish POL III as a sensor of endogenous mtDNA released during viral infection and indicate that autosomal dominant POL III haploinsufficiency may predispose individuals to critical COVID-19.

Humans