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

Silva‐Filho, João Luiz; Oliveira, Lilian Gomes de; Monteiro, Leonardo Amaral; Parise, Pierina Lorencini; Zanluqui, Nágela Ghabdan; Polonio, Carolina Manganeli; Freitas, Carla; Toledo-Teixeira, Daniel A.; Souza, William Marciel de; Bittencourt, Najara; Amorim, Mariene R.; Forato, Julia; Muraro, Stéfanie Primon; Souza, Gabriela Fabiano de; Martini, Matheus Cavalheiro; Bispos-dos-Santos, Karina; Judice, Carla C.; Costa, Maria Laura; Angerami, Rodrigo Nogueira; Freitas, André Ricardo Ribas; Resende, Mariângela Ribeiro; Garcia, Márcia Teixeira; Moretti, Maria Luíza; Rénia, Laurent; Ng, Lisa F. P.; Rothlin, Carla V.; Costa, Fabio T. M.; Peron, Jean Pierre Schatzmann; Proença-Módena, José Luiz

doi:10.1101/2021.01.27.428402

Cited by 3 publications

(3 citation statements)

References 69 publications

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“…The cells were incubated for 4 days until 70% of cytopathic effect. Subsequently, the cell culture supernatant was collected and viral replication was confirmed through real-time quantitative reverse transcription-PCR (RT-qPCR) 20 and quantified by an FFU assay in Vero cells 21 . This sample was used to assess the performance of all three methods: multiplex PCR, SMART-9N, and Rapid SMART-9N, and the metagenomics approaches, SMART-9N, and Rapid SMART-9N, was tested in different serial ten-fold MEM dilutions up to 1-1,000,000 to assess the limit of detection (Extended data: Tables S1 and S2 22 ).…”

Section: Sample Collectionmentioning

confidence: 99%

Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing

et al. 2021

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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 method 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, ‘SMART-9N’, and a version compatible with barcoded PCR primers available from Oxford Nanopore Technologies, ‘Rapid SMART-9N’, for the detection, characterization, and whole-genome sequencing of RNA viruses. 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 6e00 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.

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Section: Sample Collectionmentioning

confidence: 99%

Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing

et al. 2021

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“…Co-infections with Dengue virus (DENV) or Chikungunya (CHIKV) virus seem to exacerbate the risk and severity of the symptoms [65]. Recent work suggests that patients with neurological complications have high levels of growth arrest-specific 6 (Gas6), which promotes ZIKV infection and downmodulates the type I IFN response [115]. Another member of the Flavivirus family, DENV, is responsible for 400 million estimated infections per year and 100 million clinical manifestations, a growing global burden [116].…”

Section: (+) Ssrna Virusesmentioning

confidence: 99%

Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections

Hirschenberger

Hunszinger

Sparrer

2021

Cells

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Non-persistent viruses classically cause transient, acute infections triggering immune responses aimed at the elimination of the pathogen. Successful viruses evolved strategies to manipulate and evade these anti-viral defenses. Symptoms during the acute phase are often linked to dysregulated immune responses that disappear once the patient recovers. In some patients, however, symptoms persist or new symptoms emerge beyond the acute phase. Conditions resulting from previous transient infection are termed post-acute sequelae (PAS) and were reported for a wide range of non-persistent viruses such as rota-, influenza- or polioviruses. Here we provide an overview of non-persistent viral pathogens reported to be associated with diverse PAS, among them chronic fatigue, auto-immune disorders, or neurological complications and highlight known mechanistic details. Recently, the emergence of post-acute sequelae of COVID-19 (PASC) or long COVID highlighted the impact of PAS. Notably, PAS of non-persistent infections often resemble symptoms of persistent viral infections, defined by chronic inflammation. Inflammation maintained after the acute phase may be a key driver of PAS of non-persistent viruses. Therefore, we explore current insights into aberrant activation of innate immune signaling pathways in the post-acute phase of non-persistent viruses. Finally, conclusions are drawn and future perspectives for treatment and prevention of PAS are discussed.

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“…Genetic differences, mainly related to antiviral immune response and neurodevelopment may directly influence susceptibility to infection [18,19]. Many of these genes code for proteins involved in signaling pathways, as adaptor proteins and transcription factors.…”

Section: Introductionmentioning

confidence: 99%

ZIKV Infection and miRNA Network in Pathogenesis and Immune Response

Polonio

Peron

2021

Viruses

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Over the years, viral infections have caused severe illness in humans. Zika Virus (ZIKV) is a flavivirus transmitted by mosquito vectors that leads to notable neurological impairment, whose most dramatic impact is the Congenital ZIKV Syndrome (CZS). ZIKV targets neuronal precursor cells leading to apoptosis and further impairment of neuronal development, causing microcephaly, lissencephaly, ventriculomegaly, and calcifications. Several regulators of biological processes are involved in CZS development, and in this context, microRNAs (miRNAs) seem to have a fundamental role. miRNAs are important regulators of protein translation, as they form the RISC silencing complex and interact with complementary mRNA target sequences to further post-transcriptional repression. In this context, little is known about their participation in the pathogenesis of viral infections. In this review, we discuss how miRNAs could relate to ZIKV and other flavivirus infections.

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

Cited by 3 publications

References 69 publications

Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing

Rapid viral metagenomics using SMART-9N amplification and nanopore sequencing

Implications of Innate Immunity in Post-Acute Sequelae of Non-Persistent Viral Infections

ZIKV Infection and miRNA Network in Pathogenesis and Immune Response

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