OmniVira

Literature detail

Host serum-circulating flavivirus NS1 co-opts mosquito miRNA processing to suppress early immune defense.

Yifei Li1,2 Chunlai Cui1,2,3 Jinjin Ding1,2,3 Yiguan Wang1,2 Jiaqi Yun1,2 Fang Li1,2 Sibao Wang4,5
Affiliations 5 institutions
  1. New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.
  2. University of Chinese Academy of Sciences, Beijing, China.
  3. Shanghai Institute of Wildlife Epidemics, School of Life Sciences, East China Normal University, Shanghai, China.
  4. New Cornerstone Science Laboratory, Key Laboratory of Insect Developmental and Evolutionary Biology, State Key Laboratory of Plant Trait Design, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China. [email protected].
  5. University of Chinese Academy of Sciences, Beijing, China. [email protected].
PMID 42103722 2026 Nat Commun eng aheadofprint
PubMed DOI Browse context

Article

Publication summary

Flaviviruses pose growing global health threats and are transmitted by Aedes mosquitoes. Yet, how these viruses overcome early mosquito immunity remains unclear. Here, we reveal a cross-host immune evasion strategy in which the flavivirus NS1 protein, abundantly secreted into infected human serum, is taken up by mosquitoes during blood feeding and rapidly internalized into midgut epithelial cells-prior to viral replication. NS1 hijacks the mosquito spliceosome-associated factor Prp19 to promote miR-275-5p maturation, which suppresses the caspase gene CASPS19, blocking apoptosis and enabling early viral replication. Engineered mosquitoes expressing a miR-275 sponge show enhanced resistance to dengue and Zika viruses. These findings uncover a mechanism by which a viral protein presented in infected host blood reprograms vector gene regulation, establishing a paradigm of cross-species immune manipulation by flaviviruses.

Structured evidence records

Evidence records

1 total
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.92
Key finding

Flavivirus NS1 from infected human serum is taken up by Aedes mosquitoes during blood feeding and manipulates mosquito miRNA maturation to suppress apoptosis, enabling early viral replication.

Location
Not specified
Supporting text

‘Flavivirus NS1 protein, abundantly secreted into infected human serum, is taken up by mosquitoes during blood feeding and rapidly internalized into midgut epithelial cells.… NS1 hijacks the mosquito spliceosome-associated factor Prp19 to promote miR-275-5p maturation, which suppresses the caspase gene CASPS19, blocking apoptosis and enabling early viral replication.’

Method
protein uptake assay | gene expression analysis | engineered mosquito model
Sample type
serum | mosquito midgut epithelial cells
Study design
molecular experiment
Transmission direction
animal-to-animal
Event type
cross-species immune evasion mechanism
Genes or proteins
NS1 | Prp19 | miR-275-5p | CASPS19
Host factors
Prp19
Mechanism types
miRNA maturation regulation | apoptosis suppression