title: Dynamic viral dissemination in mice infected with yellow fever virus strain 17D.
abstract: Arboviruses such as yellow fever virus (YFV) are transmitted between arthropod vectors and vertebrate hosts. While barriers limiting arbovirus population diversity have been observed in mosquitoes, whether barriers exist in vertebrate hosts is unclear. To investigate whether arboviruses encounter bottlenecks during dissemination in the vertebrate host, we infected immunocompetent mice and immune-deficient mice lacking alpha/beta interferon (IFN-α/β) receptors (IFNAR⁻/⁻ mice) with a pool of genetically marked viruses to evaluate dissemination and host barriers. We used the live attenuated vaccine strain YFV-17D, which contains many mutations compared with virulent YFV. We found that intramuscularly injected immunocompetent mice did not develop disease and that viral dissemination was restricted. Conversely, 32% of intramuscularly injected IFNAR⁻/⁻ mice developed disease. By following the genetically marked viruses over time, we found broad dissemination in IFNAR⁻/⁻ mice followed by clearance. The patterns of viral dissemination were similar in mice that developed disease and mice that did not develop disease. Unlike our previous results with poliovirus, these results suggest that YFV-17D encounters no major barriers during dissemination within a vertebrate host in the absence of the type I IFN response.
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Erickson
authors.forename: Julie K
authors.initials: JK
authors.lastname: Pfeiffer
mesh_terms: D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000821:virology*; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000502:physiology*; D015996:Survival Rate; D019562:Viral Load; D014766:Viremia / Q000635:transmission* / Q000821:virology; D014779:Virus Replication; D015004:Yellow Fever / Q000235:genetics / Q000401:mortality / Q000821:virology*; D015005:Yellow fever virus / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D053633:Receptor, Interferon alpha-beta
references.citation: PLoS Pathog. 2005 Oct;1(2):e11
references.pmid: 16220146
references.citation: Proc Natl Acad Sci U S A. 1962 Feb;48:160-5
references.pmid: 13900302
references.citation: BMC Evol Biol. 2012 May 22;12:58
references.pmid: 22541042
references.citation: J Gen Virol. 2005 Aug;86(Pt 8):2175-2183
references.pmid: 16033965
references.citation: Infect Genet Evol. 2003 May;3(1):19-28
references.pmid: 12797969
references.citation: J Gen Virol. 1980 Jan;46(1):1-13
references.pmid: 6766176
references.citation: Science. 1930 Apr 4;71(1840):367
references.pmid: 17731835
references.citation: Virus Res. 1998 May;55(1):93-9
references.pmid: 9712515
references.citation: JAMA. 1996 Oct 9;276(14):1157-62
references.pmid: 8827969
references.citation: J Mol Evol. 2002 Feb;54(2):156-65
references.pmid: 11821909
references.citation: Curr Top Microbiol Immunol. 2006;299:285-314
references.pmid: 16568903
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5520-5
references.pmid: 16567621
references.citation: Annu Rev Microbiol. 1997;51:151-78
references.pmid: 9343347
references.citation: Proc Natl Acad Sci U S A. 1931 Jun;17(6):339-43
references.pmid: 16587631
references.citation: J Virol. 2005 Apr;79(7):4460-9
references.pmid: 15767446
references.citation: PLoS Pathog. 2009 Oct;5(10):e1000614
references.pmid: 19816561
references.citation: J Virol. 2008 Jun;82(12):6024-33
references.pmid: 18400851
references.citation: Microb Pathog. 1991 Feb;10(2):93-104
references.pmid: 1716342
references.citation: Virus Genes. 1997;14(3):225-34
references.pmid: 9311567
references.citation: Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):E2294-303
references.pmid: 22853955
references.citation: PLoS Pathog. 2012 Sep;8(9):e1002897
references.pmid: 23028310
references.citation: PLoS Pathog. 2010 Mar 05;6(3):e1000791
references.pmid: 20221252
references.citation: Nature. 2006 Jan 19;439(7074):344-8
references.pmid: 16327776
references.citation: J Exp Med. 1943 Jun 1;77(6):487-506
references.pmid: 19871299
references.citation: Proc Natl Acad Sci U S A. 2008 May 13;105(19):6970-5
references.pmid: 18458341
references.citation: J Immunol. 1971 Jul;107(1):236-43
references.pmid: 4326399
references.citation: Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16038-43
references.pmid: 21896755
references.citation: Virology. 1998 Oct 10;250(1):67-75
references.pmid: 9770421
references.citation: PLoS Pathog. 2008 Jun 06;4(6):e1000082
references.pmid: 18535656
references.citation: Nat Med. 2012 Dec;18(12):1820-6
references.pmid: 23142821
references.citation: Vaccine. 2012 May 2;30(21):3180-7
references.pmid: 22425792
references.citation: J Gen Virol. 1996 Jun;77 ( Pt 6):1277-85
references.pmid: 8683217