# Insect adaptive immunity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $507,333

## Abstract

SUMMARY
The central goal of this project is to examine antiviral immunity in insects. Insect transmission of arboviruses
causes widespread and debilitating disease across the globe. Viral replication and dissemination in the vector
are critical factors in transmission competence. RNA interference is the insect major antiviral system that
inhibits viral replication and viral dissemination throughout the insect tissues. The mechanisms involved in
developing and effective antiviral immunity are poorly understood.
We propose to study antiviral immunity in the model organism Drosophila melanogaster. We discovered that
immunity involves uptake of viral double stranded RNA by hemocytes, followed by reverse transcription to
generate viral DNAs (vDNAs) that enables amplification of the RNAi response by de novo synthesis of siRNAs
(secondary vsRNAs). Central to Drosophila immunity are macrophage-like cells, hemocytes, which are
responsible for antiviral RNAi amplification by the production of 5’-triphosphorylated secondary vsRNAs. In the
effector face, vsRNAs are incorporated into exosome-like vesicles (ELVs). Haemocyte-derived ELVs mediate
the delivery of antiviral vsRNAs to uninfected tissues and protect flies from infection at distal sites.
In striking parallel to vertebrates, flies also rely on systemic immunity to control viral infection, albeit in this
case the virus-specific signal is nucleic acid-based. We hypothesize that haemocytes take up dsRNA from
infected cells to direct the synthesis of vDNA, which in turn templates secondary vsRNA providing adaptive
immunity. We will examine (i) the mechanisms of vDNA synthesis, (ii) production and regulation of vsRNA
production and (iii) the generation of antiviral ELVs and their function in antiviral immunity.

## Key facts

- **NIH application ID:** 9985740
- **Project number:** 5R01AI137471-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Raul Andino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $507,333
- **Award type:** 5
- **Project period:** 2018-09-14 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985740

## Citation

> US National Institutes of Health, RePORTER application 9985740, Insect adaptive immunity (5R01AI137471-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9985740. Licensed CC0.

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