Project description:Host cells produce interferon (IFN) in response to viral infections. Secreted interferon results in the transcription and production of hundreds of interferon-stimulated genes (ISGs). A genome-wide CRISPR screen using IFN alpha-treated Huh7.5 cells was performed to determine which ISGs were required in order for host cells to suppress yellow fever virus (YFV) infection.
Project description:In this study, we describe a viral suppressor of RNA silencing encoded by the prototype flavivirus, yellow fever virus (YFV). We show that the YFV capsid protein inhibits RNA silencing in the mosquito Aedes aegypti by interfering with Dicer. These results suggest a molecular arms race between vector and pathogen underlies the continued existence of flaviviruses in nature.
Project description:Central questions regarding the origin of memory CD8 T cells, their turnover and longevity in vivo are not well-defined in humans. Here, we have used the highly efficacious live yellow fever virus vaccine (YFV-17D) to address these issues in the context of a primary acute viral infection. We interrogated genome-wide CpG methylation of YFV tetramer-specific CD8 T cells. These findings provide a better understanding of how memory CD8 T cells are formed and maintained in humans.
Project description:Yellow fever (YF) is a life-threatening mosquito-borne disease prevalent in South America and Africa, accounting for up to 60,000 annual deaths. Between December 2016 and May 2018, Brazil reported its worst YF outbreak this century with a fatality rate of 33.6%. While YF vaccines have shown protective capabilities, the genetic profile of those infected with the wild-type YF virus (YFV) remains uncharacterized. Building on recent findings by Kallas et al. (2019), which discerned clinical and immunological determinants of YF mortality, we conducted a comprehensive transcriptional profiling of blood samples from YFV-infected patients. Our investigation integrated omics data with clinical and immunological metrics, contrasting the wild-type YFV acute infection signature against the response triggered by the YF17D vaccine strain and the signature linked to severe COVID-19. Our analyses revealed key molecular mechanisms of YFV infection and determinants of disease severity. Notably, a comparative assessment elucidated distinct gene expression patterns between wild-type YFV infections, YF17D vaccination, and severe COVID-19. This study offers pivotal insights into the molecular underpinnings of YFV infection and its severity, potentially enhancing our comprehension of viral infections at large.
Project description:Aedes aegypti mosquitoes infect hundreds of millions of people each year with dangerous viral pathogens including dengue, yellow fever, Zika, and chikungunya. Progress in understanding the biology of this insect, and developing tools to fight it, depends on the availablity of a high-quality genome assembly. Here we use DNA proximity ligaton (Hi-C) and Pacific Biosciences long reads to create AaegL5 - a highly contiguous A. aegypti reference.