Viral paratransgenesis in the malaria vector Anopheles gambiae

Xiaoxia Ren, Egbert Hoiczyk, Jason L. Rasgon

Research output: Contribution to journalArticle

Abstract

Paratransgenesis, the genetic manipulation of insect symbiotic microorganisms, is being considered as a potential method to control vector-borne diseases such as malaria. The feasibility of paratransgenic malaria control has been hampered by the lack of candidate symbiotic microorganisms for the major vector Anopheles gambiae. In other systems, densonucleosis viruses (DNVs) are attractive agents for viral paratransgenesis because they infect important vector insects, can be genetically manipulated and are transmitted to subsequent generations. However, An. gambiae has been shown to be refractory to DNV dissemination. We discovered, cloned and characterized the first known DNV (AgDNV) capable of infection and dissemination in An. gambiae. We developed a flexible AgDNV-based expression vector to express any gene of interest in An. gambiae using a two-plasmid helper-transducer system. To demonstrate proof-of-concept of the viral paratransgenesis strategy, we used this system to transduce expression of an exogenous gene (enhanced green fluorescent protein; EGFP) in An. gambiae mosquitoes. Wild-type and EGFP-transducing AgDNV virions were highly infectious to An. gambiae larvae, disseminated to and expressed EGFP in epidemiologically relevant adult tissues such as midgut, fat body and ovaries and were transmitted to subsequent mosquito generations. These proof-of-principle data suggest that AgDNV could be used as part of a paratransgenic malaria control strategy by transduction of anti-Plasmodium peptides or insect-specific toxins in Anopheles mosquitoes. AgDNV will also be extremely valuable as an effective and easy-to-use laboratory tool for transient gene expression or RNAi in An. gambiae.

Original languageEnglish (US)
Article numbere1000135
JournalPLoS Pathogens
Volume4
Issue number8
DOIs
StatePublished - Aug 2008

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Anopheles gambiae
Malaria
Culicidae
Viruses
Insects
Insect Vectors
Gene Expression
Disease Vectors
Anopheles
Fat Body
Plasmodium
RNA Interference
Transducers
Virion
Larva
Ovary
Plasmids
Peptides
Infection

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Viral paratransgenesis in the malaria vector Anopheles gambiae. / Ren, Xiaoxia; Hoiczyk, Egbert; Rasgon, Jason L.

In: PLoS Pathogens, Vol. 4, No. 8, e1000135, 08.2008.

Research output: Contribution to journalArticle

Ren, Xiaoxia ; Hoiczyk, Egbert ; Rasgon, Jason L. / Viral paratransgenesis in the malaria vector Anopheles gambiae. In: PLoS Pathogens. 2008 ; Vol. 4, No. 8.
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