Biology subjects

Alba, K.

Publications and source records attributed to Alba, K..

3 recordsLinked to original sources

bioRxiv2026

Multi-omics Reveals Divergent Endothelial Molecular Responses to New and Old World Hantaviruses

Hantaviruses cause vascular leakage syndromes that vary in clinical manifestation and severity. Although tissue tropism contributes to these differences, both Old and New World hantaviruses infect endothelial cells, where species-specific disease phenotypes remain poorly understood. Here we integrated time-resolved global RNA sequencing, mass spectrometry proteomics, and phosphoproteomics of human endothelial cells infected with New World Andes virus (ANDV) or Old World Hantaan virus (HTNV). Despite equivalent early viral RNA and protein levels, ANDV elicited a stronger innate immune protein response, preceding its restriction while HTNV replication continued. At later stages of infection, HTNV induced downregulation of cytoskeletal and junctional protein phosphorylation, accompanied by visual disruption of cellular actin architecture. Additionally, ANDV induced heightened activity of ERBB-family kinases, whose chemical inhibition by neratinib and afatinib reduced viral replication. Together, these data define species-specific responses in endothelial cells, identify druggable host targets, and reveal mechanisms with relevance to divergent vascular leakage symptomology.

systems biology↗

bioRxiv2025

HIV-1 latency reversing agents converge on phosphoregulation of nuclear protein complexes

Despite the success of antiretroviral therapy (ART), HIV-1 persists in latently infected cells, posing a central barrier to a cure. "Shock-and-kill" strategies using latency-reversing agents (LRAs) have shown some promise in reactivating viral gene expression ex vivo, but have yielded little clinical efficacy, underscoring the need for deeper insight into the molecular mechanisms that govern reactivation. Here, we performed deep quantitative phosphoproteomics of J-Lat 10.6 cells treated with diverse LRAs: SAHA, PMA, or prostratin. We identified 48,476 confidently localized phosphorylation sites mapping to 6,672 proteins, with SAHA inducing the most extensive changes. Regulated phosphoproteins were enriched in chromatin organization, transcription, RNA processing, nuclear transport, and cytoskeletal remodeling. Although LRAs regulated overlapping pathways, they elicited divergent kinase activities and site-specific phosphorylation patterns. A reproducible core of 3,502 phosphorylation sites on 1,432 proteins mapped to 39 nuclear protein complexes, including the spliceosome, Mediator, NF-{kappa}B, and RNA polymerase II. Remarkably, 20 protein complexes were phosphoregulated by all three LRAs, but at distinct sites, revealing convergence on shared nuclear machinery through distinct mechanisms. This study provides a comprehensive map of protein complex phosphorylation remodeling during HIV-1 reactivation and highlights signaling mechanisms that could guide the rational design of next-generation LRAs with improved efficacy and reduced toxicity.

microbiology↗

bioRxiv2025

Global Landscape of Human Kinase Motifs in Viral Proteomes

Viruses are classically viewed as targets of host sensing, yet whether they also sense and respond to host cues remains largely unexplored. We propose that host-driven post-translational modification of viral proteins allows viruses to dynamically sense host cellular states. We annotated human kinase motifs in 1,505 viral proteomes and discovered an enrichment for stress, inflammation, and cell-cycle kinases. Mapping kinase motifs onto 21,606 viral protein structures and integrating with phosphoproteomics of infected cells revealed surface-accessible residues were preferentially phosphorylated, showed greater kinase specificity, and were under positive selection for stress and immune kinase motifs. Temporal phosphoproteomics of alphavirus-infected cells confirmed stress kinase activation and viral protein phosphorylation, and MAP kinase inhibition reduced alphavirus replication and phosphorylation of ERK and JNK motifs on viral proteins. Our findings suggest that viruses evolved as biosensors of the host signaling state, unveiling new antiviral opportunities aimed at disrupting virus decision-making.

microbiology↗