host alternation is necessary to maintain the genome stability of rift valley fever virus主机变更必须维持基因组稳定的裂谷热的病毒.pdfVIP

Host Alternation Is Necessary to Maintain the Genome Stability of Rift Valley Fever Virus 1¤ 2 3 ´ 3 2 Sara Moutailler , Benjamin Roche , Jean-Michel Thiberge , Valerie Caro , Franc¸ois Rougeon , Anna- Bella Failloux1* 1 Molecular Genetics of Bunyavirus, Department of Virology, Institut Pasteur, Paris, France, 2 Developmental Genetics and Biochemistry, Department of Immunology, Institut Pasteur, Paris, France, 3 Genotyping of Pathogens and Public Health, Department of Infection and Epidemiology, Institut Pasteur, Paris, France Abstract Background: Most arthropod-borne viruses (arboviruses) are RNA viruses, which are maintained in nature by replication cycles that alternate between arthropod and vertebrate hosts. Arboviruses appear to experience lower rates of evolution than RNA viruses that replicate in a single host. This genetic stability is assumed to result from a fitness trade-off imposed by host alternation, which constrains arbovirus genome evolution. To test this hypothesis, we used Rift Valley fever virus (RVFV), an arbovirus that can be transmitted either directly (between vertebrates during the manipulation of infected tissues, and between mosquitoes by vertical transmission) or indirectly (from one vertebrate to another by mosquito-borne transmission). Methodology/Principal Findings: RVFV was serially passaged in BHK21 (hamster) or Aag2 (Aedes aegypti) cells, or in alternation between the two cell types. After 30 passages, these single host-passaged viruses lost their virulence and induced protective effects against a challenge with a virulent virus. Large deletions in the NSs gene that encodes the virulence factor were dete