Influenza A virus remains a major public health problem. Mouse models have been widely used to study influenza infection in mammals. DBA/2J and C57BL/6J represent extremes in terms of susceptibility to influenza A infection among inbred laboratory mouse strains. Several studies focused specifically on the factors responsible for the susceptibility of DBA/2J or the resistance of C57BL/6J and resulted in impressive lists of candidate genes or factors over- or underexpressed in one of the strains. We adopted a different phenotypical approach to identify the critical steps of the infection process accounting for the differences between DBA/2J and C57BL/6J strains. We concluded that both a dysfunction of alveolar macrophages and an increased permissivity of respiratory cells rendered DBA/2J more susceptible to influenza infection.
Get full access to this article
View all access options for this article.
References
1.
AlbertsR, SrivastavaB, WuH, ViegasN, GeffersR, KlawonnF, NovoselovaN, do ValleTZ, PanthierJJ, SchughartK. 2010. Gene expression changes in the host response between resistant and susceptible inbred mouse strains after influenza A infection. Microbes Infect, 12(4):309–318.
2.
AshmanRB, PapadimitrioubJM, FulurijaA, DrysdaleKE, FarahCS, NaidooO, GotjamanosT. 2003. Role of complement C5 and T lymphocytes in pathogenesis of disseminated and mucosal candidiasis in susceptible DBA/2 mice. Microb Pathog, 34(2):103–113.
3.
BlazejewskaP, KoscinskiL, ViegasN, AnhlanD, LudwigS, SchughartK. 2011. Pathogenicity of different PR8 influenza A virus variants in mice is determined by both viral and host factors. Virology, 412(1):36–45.
4.
BoonAC, deBeauchampJ, HollmannA, LukeJ, KotbM, RoweS, FinkelsteinD, NealeG, LuL, WilliamsRW, WebbyRJ. 2009. Host genetic variation affects resistance to infection with a highly pathogenic H5N1 influenza A virus in mice. J Virol, 83(20):10417–10426.
5.
BoonAC, WilliamsRW, SinasacDS, WebbyRJ. 2014. A novel genetic locus linked to pro-inflammatory cytokines after virulent H5N1 virus infection in mice. BMC Genomics, 15(1):1017.
6.
BradleyPP, ChristensenRD, RothsteinG. 1982. Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood, 60(3):618–622.
7.
BrummerE, StevensDA. 1994. Anticryptococcal activity of macrophages: role of mouse strain, C5, contact, phagocytosis, and L-arginine. Cell Immunol, 157(1):1–10.
8.
de GraafM, FouchierRA. 2014. Role of receptor binding specificity in influenza A virus transmission and pathogenesis. EMBO J, 33(8):823–841.
9.
DenglerL, KuhnN, ShinDL, HatesuerB, SchughartK, WilkE. 2014. Cellular changes in blood indicate severe respiratory disease during influenza infections in mice. PLoS One, 9(7):e103149.
10.
DenglerL, MayM, WilkE, BahgatMM, SchughartK. 2012. Immunization with live virus vaccine protects highly susceptible DBA/2J mice from lethal influenza A H1N1 infection. Virol J, 9:212.
11.
DermineM. 2013. Testing candidate effectors contributing to resistance to pneumoviruses. PhD thesis. Department of Morphology and Pathology, Faculty of Veterinary Medicine, University of Liege, Liège, Belgique. http://orbi.ulg.ac.be/handle/2268/160080 (pp 104–105).
12.
EdingerTO, PohlMO, StertzS. 2014. Entry of influenza A virus: host factors and antiviral targets. J Gen Virol, 95 (Pt 2):263–277.
13.
GariglianyMM, CornetA, DesmechtD. 2012. Human/bovine chimeric MxA-like GTPases reveal a contribution of N-terminal domains to the magnitude of anti-influenza A activity. J Interferon Cytokine Res, 32(7):326–331.
14.
GariglianyMM, HabyarimanaA, LambrechtB, Van de PaarE, CornetA, van den BergT, DesmechtD. 2010. Influenza A strain-dependent pathogenesis in fatal H1N1 and H5N1 subtype infections of mice. Emerg Infect Dis, 16(4):595–603.
15.
GlaserL, ConenelloG, PaulsonJ, PaleseP. 2007. Effective replication of human influenza viruses in mice lacking a major alpha2,6 sialyltransferase. Virus Res, 126(1–2):9–18.
HerboldW, MausR, HahnI, DingN, SrivastavaM, ChristmanJW, MackM, ReutershanJ, BrilesDE, PatonJC, WinterC, WelteT, MausUA. 2010. Importance of CXC chemokine receptor 2 in alveolar neutrophil and exudate macrophage recruitment in response to pneumococcal lung infection. Infect Immun, 78(6):2620–2630.
18.
HicksJT, EnnisFA, KimE, VerbonitzM. 1978. The importance of an intact complement pathway in recovery from a primary viral infection: influenza in decomplemented and in C5-deficient mice. J Immunol, 121(4):1437–1445.
19.
KeletaL, IbricevicA, BovinNV, BrodySL, BrownEG. 2008. Experimental evolution of human influenza virus H3 hemagglutinin in the mouse lung identifies adaptative regions in HA1 and HA2. J Virol, 82(23):11599–11608.
20.
KlepserME. 2014. Socioeconomic impact of seasonal (epidemic) influenza and the role of over-the-counter medicines. Drugs, 74(13):1467–1479.
LiberatiTA, TrammellRA, RandleM, BarrettS, TothLA. 2013. Cytokine and chemokine responses of lung exposed to surrogate viral and bacterial infections. Comp Med, 63(2):114–126.
23.
Mahmutovic-PerssonI, AkbarshahiH, BartlettNW, GlanvilleN, JohnstonSL, BrandeliusA, UllerL. 2014. Inhaled dsRNA and rhinovirus evoke neutrophilic exacerbation and lung expression of thymic stromal lymphopoietin in allergic mice with established experimental asthma. Allergy, 69(3):348–358.
24.
MarquisJF, LacourseR, RyanL, NorthRJ, GrosP. 2009. Genetic and functional characterization of the mouse Trl3 locus in defense against tuberculosis. J Immunol, 182(6):3757–3767.
25.
MurrayCJ, LopezAD, ChinB, FeehanD, HillKH. 2006. Estimation of potential global pandemic influenza mortality on the basis of vital registry data from the 1918–20 pandemic: a quantitative analysis. Lancet, 368(9554):2211–2218.
26.
NedelkoT, KollmusH, KlawonnF, SpijkerS, LuL, HessmanM, AlbertsR, WilliamsRW, SchughartK. 2012. Distinct gene loci control the host response to influenza H1N1 virus infection in a time-dependent manner. BMC Genomics, 13:411.
27.
NingZY, NingZY, LuoMY, QiWB, YuB, JiaoPR, LiaoM. 2007. Detection of expression of influenza virus receptors in tissues of BALB/c mice by histochemistry. 2009. Vet Res Commun, 33(8): 895–903.
28.
PattenCCJr., MylesMH, FranklinCL, LivingstonRS. 2010. Perturbations in cytokine gene expression after inoculation of C57BL/6 mice with Pasteurella pneumotropica. Comp Med, 60(1):18–24.
29.
PreaudE, DurandL, MacabeoB, FarkasN, SloesenB, PalacheA, ShupoF, SamsonSI; Vaccines Europe influenza working group. 2014. Annual public health and economic benefits of seasonal influenza vaccination: a European estimate. BMC Public Health, 14:813.
30.
PreusseM, TantawyMA, KlawonnF, SchughartK, PesslerF. 2013. Infection- and procedure-dependent effects on pulmonary gene expression in the early phase of influenza A virus infection in mice. BMC Microbiol, 13:293.
31.
ShimizuM, YamaguchiM, FujitaS, UtsunomiyaT, YamamotoH, KasaiK. 2013. Interleukin-17/T-helper 17 cells in an atopic dermatitis mouse model aggravate orthodontic root resorption in dental pulp. Eur J Oral Sci, 121(2):101–110.
32.
SmeenkCA, WrightKE, BurnsBF, ThakerAJ, BrownEG. 1996. Mutations in the hemagglutinin and matrix genes of a virulent influenza virus variant, A/FM/1/47-MA, control different stages in pathogenesis. Virus Res, 44(2):79–95.
33.
SrivastavaB, BlazejewskaP, HessmannM, BruderD, GeffersR, MauelS, GruberAD, SchughartK. 2009. Host genetic background strongly influences the response to influenza a virus infections. PLoS One, 4(3):e4857.
34.
TateMD, PickettDL, van RooijenN, BrooksAG, ReadingPC. 2010. Critical role of airway macrophages in modulating disease severity during influenza virus infection of mice. J Virol, 84(15):7569–7580.
35.
TrammellRA, LiberatiTA, TothLA. 2012. Host genetic background and the innate inflammatory response of lung to influenza virus. Microbes Infect, 14(1):50–58.
36.
TrammellRA, TothLA. 2011. Markers for predicting death as an outcome for mice used in infectious disease research. Comp Med, 61(6):492–498.
37.
WangL, JiaoY, CaoY, LiuG, WangY, GuW. 2014. Limitation of number of strains and persistence of false positive loci in QTL mapping using recombinant inbred strains. PLoS One, 9(7):e102307.
38.
WetselRA, FleischerDT, HavilandDL. 1990. Deficiency of the murine fifth complement component (C5). A 2-base pair gene deletion in a 5′-exon. J Biol Chem, 265(5):2435–2440.
39.
World Health Organization (WHO). 2012. Vaccines against influenza WHO position paper–November 2012. Wkly Epidemiol Rec, 47:461–476.
40.
ZaraketH, BridgesOA, RussellCJ. 2013. The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus replication and pathogenesis in mice. J Virol, 87(9):4826–4834.
