West Nile Virus Genetic Diversity is Maintained during Transmission by Culex pipiens quinquefasciatus Mosquitoes

University of Texas Medical Branch, United States of America
PLoS ONE (Impact Factor: 3.23). 09/2011; 6(9):e24466. DOI: 10.1371/journal.pone.0024466
Source: PubMed


Due to error-prone replication, RNA viruses exist within hosts as a heterogeneous population of non-identical, but related viral variants. These populations may undergo bottlenecks during transmission that stochastically reduce variability leading to fitness declines. Such bottlenecks have been documented for several single-host RNA viruses, but their role in the population biology of obligate two-host viruses such as arthropod-borne viruses (arboviruses) in vivo is unclear, but of central importance in understanding arbovirus persistence and emergence. Therefore, we tracked the composition of West Nile virus (WNV; Flaviviridae, Flavivirus) populations during infection of the vector mosquito, Culex pipiens quinquefasciatus to determine whether WNV populations undergo bottlenecks during transmission by this host. Quantitative, qualitative and phylogenetic analyses of WNV sequences in mosquito midguts, hemolymph and saliva failed to document reductions in genetic diversity during mosquito infection. Further, migration analysis of individual viral variants revealed that while there was some evidence of compartmentalization, anatomical barriers do not impose genetic bottlenecks on WNV populations. Together, these data suggest that the complexity of WNV populations are not significantly diminished during the extrinsic incubation period of mosquitoes.

Download full-text


Available from: Eleanor R Deardorff
  • Source
    • "Previous studies suggest that arboviruses in natural systems may have the capacity to utilize complementation to maintain non-viable variants in co-infecting cells [10-12], suggesting that such interactions could also readily occur among variants with more intermediate fitness levels. Experimental studies with VSV have shown that relative fitness is MOI-dependent due to increased levels of strain complementation [13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: RNA viruses including arthropod-borne viruses (arboviruses) exist as highly genetically diverse mutant swarms within individual hosts. A more complete understanding of the phenotypic correlates of these diverse swarms is needed in order to equate RNA swarm breadth and composition to specific adaptive and evolutionary outcomes. Here, we determined clonal fitness landscapes of mosquito cell-adapted West Nile virus (WNV) and assessed how altering the capacity for interactions among variants affects mutant swarm dynamics and swarm fitness. Our results demonstrate that although there is significant mutational robustness in the WNV swarm, genetic diversity also corresponds to substantial phenotypic diversity in terms of relative fitness in vitro. In addition, our data demonstrate that increasing levels of co-infection can lead to widespread strain complementation, which acts to maintain high levels of phenotypic and genetic diversity and potentially slow selection for individual variants. Lastly, we show that cooperative interactions may lead to swarm fitness levels which exceed the relative fitness levels of any individual genotype. These studies demonstrate the profound effects variant interactions can have on arbovirus evolution and adaptation, and provide a baseline by which to study the impact of this phenomenon in natural systems.
    Full-text · Article · Apr 2012 · BMC Evolutionary Biology
  • Source
    • "Conversely, identical non-consensus WNV genomes have been detected in intrahost populations infecting birds in a single transmission focus, suggesting that population bottlenecks may not be as restrictive as had been assumed (Jerzak et al., 2005), and defective DENV genomes appear to perpetuate in transmission cycles through complementation (Aaskov et al., 2006). Supporting this, Brackney et al. recently failed to document significant population bottlenecks during infection of Cx. quinquefasciatus mosquitoes by WNV (Brackney et al., 2011). It may be that the importance of bottlenecks during arbovirus transmission is a function of the specific virus–host system under study, and not consistent across systems. "
    [Show abstract] [Hide abstract]
    ABSTRACT: West Nile virus (WNV) (Flaviviridae: Flavivirus) is transmitted from mosquitoes to birds, but can cause fatal encephalitis in infected humans. Since its introduction into North America in New York in 1999, it has spread throughout the western hemisphere. Multiple outbreaks have also occurred in Europe over the last 20 years. This review highlights recent efforts to understand how host pressures impact viral population genetics, genotypic and phenotypic changes which have occurred in the WNV genome as it adapts to this novel environment, and molecular epidemiology of WNV worldwide. Future research directions are also discussed.
    Full-text · Article · Mar 2012 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
  • Source
    • "Dissemination rate has been correlated with body titers in WNV infected mosquitoes, so a reduction of body titer through resource competition could have led to the reduced dissemination rates observed in mosquitoes exposed to virus containing internally deleted genomes, despite the fact that no internally deleted genomes were detected in disseminated tissues (Anderson et al., 2010). The restriction of this deletion mutant to mosquito midgut may be due to physiological barriers, such as the midgut escape barrier, but other studies have found deleterious mutants in multiple mosquito tissues or multiple vectors and hosts over time (Aaskov et al., 2006; Brackney et al. 2011). Overall these results indicate the internally deleted genomes are able to interfere with the first stage of mosquito infection, which could have a downstream impact on transmission . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Most RNA viruses exist in their hosts as a heterogeneous population of related variants. Due to error prone replication, mutants are constantly generated which may differ in individual fitness from the population as a whole. Here we characterize three WNV isolates that contain, along with full-length genomes, mutants with large internal deletions to structural and nonstructural protein-coding regions. The isolates were all obtained from lorikeets that died from WNV at the Rio Grande Zoo in Albuquerque, NM between 2005 and 2007. The deletions are approximately 2kb, in frame, and result in the elimination of the complete envelope, and portions of the prM and NS-1 proteins. In Vero cell culture, these internally deleted WNV genomes function as defective interfering particles, reducing the production of full-length virus when introduced at high multiplicities of infection. In mosquitoes, the shortened WNV genomes reduced infection and dissemination rates, and virus titers overall, and were not detected in legs or salivary secretions at 14 or 21 days post-infection. In mice, inoculation with internally deleted genomes did not attenuate pathogenesis relative to full-length or infectious clone derived virus, and shortened genomes were not detected in mice at the time of death. These observations provide evidence that large deletions may occur within flavivirus populations more frequently than has generally been appreciated and suggest that they impact population phenotype minimally. Additionally, our findings suggest that highly similar mutants may frequently occur in particular vertebrate hosts.
    Full-text · Article · Feb 2012 · Virology
Show more