The West Nile virus mutant spectrum is host-dependant and a determinant of mortality in mice - PubMed (original) (raw)

The West Nile virus mutant spectrum is host-dependant and a determinant of mortality in mice

Greta V S Jerzak et al. Virology. 2007.

Abstract

To define the impact of mosquitoes and birds on intrahost WNV population dynamics, the mutant spectra that arose as a result of 20 serial in vivo passages in Culex pipiens and young chickens were examined. Genetically homogeneous WNV was serially passaged 20 times in each host. Genetic diversity was greater in mosquito-passaged WNV compared to chicken-passaged WNV. Changes in the viral consensus sequence occurred in WNV passaged in mosquitoes earlier and more frequently than in chicken-passaged WNV. Analysis of synonymous and nonsynonymous variation suggested that purifying selection was relaxed during passage in mosquitoes. Mortality in mice was significantly negatively correlated with the size of the WNV mutant spectrum. These studies suggest that mosquitoes serve as sources for WNV genetic diversity, that birds are selective sieves, and that both the consensus sequence and the mutant spectrum contribute to WNV phenotype.

PubMed Disclaimer

Figures

Figure 1.

Mean titer of WNV during sequential passage in mosquitoes (A) and chickens (B). Each of three independent lineages (designated A–F) per host type is shown.

Figure 2.

Host‐dependence of the WNV mutant spectrum. WNV derived from an infectious cDNA clone was passaged 20 times in either chickens or mosquitoes, and the mutant spectrum was characterized at passages 1, 5, 10, 15 and 20. Panels A and C: proportion of nucleotides sequenced that differed from the specimen‐specific consensus sequence in chicken (A) and mosquito (C) passaged WNV. Open symbols indicate values for each of three replicate lineages, designated G, W and R for chickens and A, B, and C for mosquitoes. Solid line indicates background error rate as determined by analysis of clone‐derived WNV, dotted line indicates homologous field‐derived observation (Jerzak, Bernard et al., 2005). Panels B and D: proportion of clones that differed from the specimen‐specific consensus sequence and chicken (B) and mosquito (D) passaged WNV. Open symbols, solid and dotted lines are as above.

Figure 3.

Survival of mice infected with (A) chicken‐ and (B) mosquito‐passed WNV. Groups of eight six‐week‐old female C3H mice were inoculated subcutaneously in the left rear footpad with 102.5 PFU of WNV and survival was monitored. Mock‐inoculated mice (not shown) remained healthy for the duration of the study. Results were obtained from two independent trials, and the survival curve for mice inoculated with the parental (unpassed) WNV is the combined data from both trials. Lineages are designated R, G and W for chick‐passaged and A, B, and C for mosquito‐passaged lineages. (C): percentage mortality at the study conclusion was significantly negatively correlated with overall genetic diversity in the inoculum.

Cited by

Genetic Drift during Systemic Arbovirus Infection of Mosquito Vectors Leads to Decreased Relative Fitness during Host Switching.
Grubaugh ND, Weger-Lucarelli J, Murrieta RA, Fauver JR, Garcia-Luna SM, Prasad AN, Black WC 4th, Ebel GD. Grubaugh ND, et al. Cell Host Microbe. 2016 Apr 13;19(4):481-92. doi: 10.1016/j.chom.2016.03.002. Epub 2016 Mar 31. Cell Host Microbe. 2016. PMID: 27049584 Free PMC article.
Experimental evolution of an RNA virus in wild birds: evidence for host-dependent impacts on population structure and competitive fitness.
Grubaugh ND, Smith DR, Brackney DE, Bosco-Lauth AM, Fauver JR, Campbell CL, Felix TA, Romo H, Duggal NK, Dietrich EA, Eike T, Beane JE, Bowen RA, Black WC, Brault AC, Ebel GD. Grubaugh ND, et al. PLoS Pathog. 2015 May 20;11(5):e1004874. doi: 10.1371/journal.ppat.1004874. eCollection 2015 May. PLoS Pathog. 2015. PMID: 25993022 Free PMC article.
Dengue--quo tu et quo vadis?
Chen R, Vasilakis N. Chen R, et al. Viruses. 2011 Sep;3(9):1562-608. doi: 10.3390/v3091562. Epub 2011 Sep 1. Viruses. 2011. PMID: 21994796 Free PMC article. Review.
Temporal and spatial alterations in mutant swarm size of St. Louis encephalitis virus in mosquito hosts.
Ciota AT, Koch EM, Willsey GG, Davis LJ, Jerzak GV, Ehrbar DJ, Wilke CO, Kramer LD. Ciota AT, et al. Infect Genet Evol. 2011 Mar;11(2):460-8. doi: 10.1016/j.meegid.2010.12.007. Epub 2011 Jan 5. Infect Genet Evol. 2011. PMID: 21215334 Free PMC article.
Vector-virus interactions and transmission dynamics of West Nile virus.
Ciota AT, Kramer LD. Ciota AT, et al. Viruses. 2013 Dec 9;5(12):3021-47. doi: 10.3390/v5123021. Viruses. 2013. PMID: 24351794 Free PMC article. Review.

References

1. Aaskov J, Buzacott K, Thu HM, Lowry K, Holmes EC. Long‐term transmission of defective RNA viruses in humans and Aedes mosquitoes. Science. 2006;311:236–238. - PubMed
1. Beasley DW, Li L, Suderman MT, Barrett AD. Mouse neuroinvasive phenotype of West Nile virus strains varies depending upon virus genotype. Virology. 2002;296:17–23. - PubMed
1. Bonneau KR, Mullens BA, MacLachlan NJ. Occurrence of genetic drift and founder effect during quasispecies evolution of the VP2 and NS3/NS3A genes of bluetongue virus upon passage between sheep, cattle, and Culicoides sonorensis. J Virol. 2001;75:8298–8305. - PMC - PubMed
1. Davis CT, Ebel GD, Lanciotti RS, Brault AC, Guzman H, Siirin M, Lambert A, Parsons RE, Beasley DW, Novak RJ, Elizondo‐Quiroga D, Green EN, Young DS, Stark LM, Drebot MA, Artsob H, Tesh RB, Kramer LD, Barrett AD. Phylogenetic analysis of North American West Nile virus isolates, 2001–2004: evidence for the emergence of a dominant genotype. Virology. 2005;342:252–265. - PubMed
1. Domingo E, Escarmis C, Martinez MA, Martinez‐Salas E, Mateu MG. Foot‐and‐mouth disease virus populations are quasispecies. Curr.Top.Microbiol.Immunol. 1992;176:33–47. - PubMed

The West Nile virus mutant spectrum is host-dependant and a determinant of mortality in mice - PubMed (original) (raw)