Mosquitoes are pathogen vectors embedded within diverse microbial ecosystems. However, the nature and interactions among their multi-kingdom microbiome remain poorly understood. We conducted a nationwide single-mosquito meta-transcriptomic survey of 5,163 mosquitoes representing 100 species across China, integrating viral discovery with marker-gene profiling of bacteria, archaea, fungi, and other eukaryotic microbes. From this, we identified 1,606 microbial species-level taxa, including extensive novel diversity, and revealed pronounced host species– specific organization of mosquito-associated communities. We detected 34 pathogens or potential pathogens of human or animal relevance, whose prevalence, abundance, host range, and geographic distribution defined distinct epidemiological patterns. Network analysis uncovered pervasive cross-kingdom microbial associations, including candidate antiviral relationships involving Wolbachia and other microbial taxa. Our study establishes a detailed view of the full-spectrum microbiome and provides a resource and conceptual framework for studying vector competence, pathogen emergence, and microbiome-informed mosquito-borne disease control.
Qin-yu Gou, Wei-Chen Wu, Pei-Bo Shi et al.· bioRxiv· 0 citations
Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that regulates diverse cellular responses, including antiviral immunity, through its conjugation to proteins in a process known as ISGylation. Several pathogens, including SARS-CoV-2, subvert ISGylation by encoding deISGylating enzymes. However, the direct targets and physiological consequences of coronaviral deISGylation remain poorly defined. Here, we genetically ablated the deISGylating activity of the SARS-CoV-2-encoded papain-like protease (PLpro) and found that loss of deISGylation boosted innate immune activation, attenuated viral replication, and promoted viral clearance in human cells and mice. Metabolomics, ISGylome proteomics, and functional analyses revealed that PLpro deISGylation relieved metabolic restriction of virus infection by directly regulating the activity of key enzymes controlling glycolysis, the pentose phosphate pathway, and redox homeostasis. These findings provide fundamental insight into how reversible ISGylation regulates immunity and metabolic processes at the molecular level and highlight viral deISGylation as a major strategy to overcome host immunometabolic defenses.
