title: Infection and transmission of Rift Valley fever viruses lacking the NSs and/or NSm genes in mosquitoes: potential role for NSm in mosquito infection.
abstract: BACKGROUND
  Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors.
  
  
  RESULTS
  Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus.
  
  
  CONCLUSIONS
  In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes.
authors.affiliation: Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, United States of America. mcrabtree@cdc.gov
authors.forename: Mary B
authors.initials: MB
authors.lastname: Crabtree
authors.forename: Rebekah J
authors.initials: RJ
authors.lastname: Kent Crockett
authors.forename: Brian H
authors.initials: BH
authors.lastname: Bird
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
authors.forename: Bobbie Rae
authors.initials: BR
authors.lastname: Erickson
authors.forename: Brad J
authors.initials: BJ
authors.lastname: Biggerstaff
authors.forename: Kalanthe
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Barry R
authors.initials: BR
authors.lastname: Miller
mesh_terms: D000330:Aedes / Q000821:virology*; D000349:Africa; D000818:Animals; D003465:Culex / Q000821:virology*; D017353:Gene Deletion; D006801:Humans; D012295:Rift Valley Fever / Q000635:transmission* / Q000821:virology*; D012296:Rift Valley fever virus / Q000235:genetics* / Q000302:isolation & purification; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D017361:Viral Nonstructural Proteins; D037521:Virulence Factors