The SARS-CoV-2 nucleocapsid (N) protein is one of the most highly expressed proteins during infection and plays crucial roles in the protection and packaging of viral RNA, replication, suppression of the immune response and virus assembly. The N gene and the overlapping accessory open reading frame ORF9b have continually evolved throughout the circulation of the virus, likely due to ongoing adaptation to the human host. This genetic variability influences the interplay of the N protein and its interactors. Yet, little is known about how specific mutations within the N/ORF9b locus of Variants of Concern (VOCs) shape the progression and outcome of infection. Here, we use a multi-omics approach to decipher how these genetic alterations reprogram the host cell by creating Wuhan-Hu-1-based recombinant viruses carrying an isogenic backbone with respective N mutations from the VOCs (called rNs) and comparing their effects at the transcriptome and proteome levels. We found that the mutations induce distinct transcriptional and translational alterations: rN-Alpha drives a stealth-like infection characterized by sustained translation efficiency and specific evasion of the 2’-5’-oligoadenylate synthetase (OAS) innate immune sensor, whereas rN-Delta and rN-BA.2 trigger a highly elevated inflammatory response. For rN-Delta, hyperphosphorylation of the N-protein drives cellular stress culminating in necroptotic cell death. Because these viruses differ only within the N/ORF9b locus, N sequence variation emerges as a determinant of infection outcome in its own right, warranting increased surveillance attention.
J. Berger, Jonas Schröder, Timothy K. Soh et al.· bioRxiv· 0 citations
Herpesvirus virions form by remodeling of intracellular virus-host interaction networks into evolutionarily conserved particle architectures. Here, we define a virion-wide spatial and quantitative protein proximity map of herpes simplex virus 1 (HSV-1) by combining cross-linking mass spectrometry with quantitative proteomics. Integration with intracellular interaction maps reveals that maturation acts as a selective filter, transforming broad virus-host associations into an organized virion network. This process depletes biosynthetic and nuclear components while enriching interactions involved in tegument organization and envelope acquisition around the viral protein UL49. Comparison with analogous maps of human cytomegalovirus (HCMV) identifies HSV-1-UL49 and HCMV-UL32 as functionally equivalent network hubs despite lacking evolutionary relatedness. Both hubs converge on shared phosphoregulatory host factors, short linear interaction motifs, and liquid-liquid phase separation. At the virion surface, the host complement regulator CD59 protects particles from complement-mediated inactivation. Together, these findings show how conserved organizational principles shape virus-specific virion interaction networks during herpesvirus maturation.
Lars Mühlberg, Yannick Jensen, Julia Ruta et al.· bioRxiv· 0 citations
The findings show that bacterial virulence can be regulated through environmentally controlled transitions between protein assemblies, identifying membrane accumulation as a promising anti-virulence target.
Sambhasan Banerjee, V. Skoryk, Bader Rayan et al.· bioRxiv· 0 citations
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