Examinando por Autor "Retamal-Diaz, Angello"

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    HSV-1 alters lipid metabolism and induces lipid droplet accumulation in functionally impaired mouse dendritic cells
    (Cell Press, 2025) Farias, Monica A; Cancino, Felipe A; Navarro, Areli J; Duarte, Luisa F; Soto, Abel A; Tognarelli, Eduardo I; Ramm, Maximiliano J; Alarcon-Zapata, Barbara N; Cordero, Jose; Martin, Sergio San; Agurto-Munoz, Cristian; Retamal-Diaz, Angello; Riedel, Claudia A; Barrera, Nelson P; Bustamante, Luis; Bueno, Susan M; Kalergis, Alexis M; Gonzalez, Pablo A
    Herpes simplex virus type 1 (HSV-1) significantly impairs dendritic cell (DC) function, ultimately eliciting the death of these cells. Here, we sought to assess whether HSV-1 modulates lipid metabolism in mouse DCs as a mechanism of immune evasion. For this, we performed RT-qPCR gene arrays with ingenuity pathway analysis (IPA), RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA), confocal microscopy, transmission electron microscopy, ultra-high-performance liquid chromatography-quadrupole time-of-flight (UHPLC-QTOF) analysis, pharmacological inhibition of eight lipid-metabolism-related enzymes in HSV-1-infected DCs, co-cultures between virus-specific transgenic CD4+ and CD8+ T cells and HSV-1-infected DCs, and in vivo assays with mice. We found that HSV-1 significantly alters lipid metabolism in DCs and induces lipid droplet (LD) accumulation in these cells. Pharmacological inhibition of two particular lipid metabolism enzymes was found to partially restore DC function. Overall, these results suggest that lipid metabolism plays an important role in the impairment of DC function by HSV-1.
  • Miniatura
    Ítem
    Role of human herpesvirus homologs of infected cell protein 27 (ICP27) in the biogenesis, processing, and maturation of mRNAs
    (American Society for Microbiology, 2025) Soto-Machuca, Abel A; Ortiz, Gerardo E; Carbone-Schellman, Javier; Pasten-Ferrada, Ignacio A; Retamal-Diaz, Angello; Kalergis, Alexis M; Gonzalez, Pablo A
    Herpesviruses are enveloped viruses with large double-stranded DNAgenomes that are highly prevalent in the human population and elicit numeroustypes of clinical manifestations, from mild to severe. These viruses are classified intothree subfamilies: alpha-, beta-, and gammaherpesvirinae, all capable of establishinglife-long persistent infections in the host. As strict intracellular parasites, these viruseshave evolved molecular determinants to support and modulate viral and host genetranscription processes during infection and the translation of messenger RNAs (mRNAs)to synthesize proteins that participate in cellular pathways promoting their replicationcycles and virion formation. Notably, some of these proteins have functional RNA-binding domains consisting of arginine-glycine-glycine (RGG) amino acid (aa) sequencesthat, when methylated, regulate their nucleic acid-binding capacities and can influencethe export of mRNAs lacking introns from the nucleus into the cytoplasm. Additionaldomains and motifs in these proteins mediate their interactions with regulatory proteinsrelated to RNA splicing, either promoting or repressing mRNA processing. Notably, allhuman herpesviruses (HHVs) encode in their genomes proteins that share homologywith infected cell protein 27 (ICP27) of herpes simplex virus type 1 (HSV-1), which cansignificantly impact the biogenesis of mRNAs and their processing during infection. Here,we review and discuss the roles of ICP27 and the corresponding homologs encoded indifferent human herpesviruses, focusing on their similarities and differences in structureand function. A more profound knowledge of the role of key viral factors requiredfor effective herpesvirus replication could aid in the design and identification of novelantivirals to treat the diseases produced by these viruses.