The ZIKV NS5 Protein Aberrantly Alters the Tubulin Cytoskeleton, Induces the Accumulation of Autophagic p62 and Affects IFN Production: HDAC6 Has Emerged as an Anti-NS5/ZIKV Factor

• DOI: 10.20944/preprints202402.1747.v1
• Publication Date: 2024-03-06T02:50:00Z
• Authors: Silvia Pérez-Yanes; Iria Lorenzo-Sánchez; Romina Cabrera-Ro...; Jonay García-Luis; Rodrigo Trujillo-...; Judith Estévez-He...; Agustín Valenzuel...
• Keywords: HDAC6

Zika virus (ZIKV) infection and pathogenesis are linked to the disruption of neurogenesis, congenital syndrome microcephaly by affecting neural progenitor cells. Nonstructural protein 5 (NS5) is largest product encoded ZIKV-RNA important for replication immune evasion. Here, we studied potential effects NS5 on microtubules (MTs) autophagy flux, together with interplay histone deacetylase 6 (HDAC6). Fluorescence microscopy, biochemical cell-fractionation combined use HDAC6 mutants, chemical inhibitors RNA interference indicated that accumulates in nuclear structures strongly promotes acetylation MTs aberrantly reorganize nested-like structures. Similarly, p62 protein, an autophagic-flux marker. Therefore, alters events under control autophagic tubulin-deacetylase HDAC6. appears degrade a deacetylase- BUZ domain-dependent manner cytoplasmic expression NS5. Moreover, inhibits RNA-mediated RIG-I interferon (IFN) production, resulting greater activity when inhibited (i.e., effect correlated stability). it conceivable contributes cell toxicity pathogenesis, evading IFN-immune response overcoming functions. has emerged as anti-ZIKV factor targeting