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Comparative Study
. 2008 May;22(4):503-16.
doi: 10.1016/j.bbi.2007.10.005. Epub 2007 Nov 28.

Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats

Michele F Hannah  1 , Vladimir B Bajic, Sabra L Klein
Affiliations
Comparative Study

Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats

Michele F Hannah et al. Brain Behav Immun. 2008 May.

Abstract

Among rodents that carry hantaviruses, more males are infected than females. Male rats also have elevated copies of Seoul virus RNA and reduced transcription of immune-related genes in the lungs than females. To further characterize sex differences in antiviral defenses and whether these differences are mediated by gonadal hormones, we examined viral RNA in the lungs, virus shedding in saliva, and antiviral defenses among male and female rats that were intact, gonadectomized neonatally, or gonadectomized in adulthood. Following inoculation with Seoul virus, high amounts viral RNA persisted longer in lungs from intact males than intact females. Removal of the gonads in males reduced the amount of viral RNA to levels comparable with intact females at 40 days post-inoculation (p.i.). Intact males shed more virus in saliva than intact females 15 days p.i.; removal of the gonads during either the neonatal period or in adulthood increased virus shedding in females and decreased virus shedding in males. Induction of pattern recognition receptors (PRRs; Tlr7 and Rig-I), expression of antiviral genes (Myd88, Visa, Jun, Irf7, Ifnbeta, Ifnar1, Jak2, Stat3, and Mx2), and production of Mx protein was elevated in the lungs of intact females compared with intact males. Gonadectomy had more robust effects on the induction of PRRs than on downstream IFNbeta or Mx2 expression. Putative androgen and estrogen response elements are present in the promoters of several of these antiviral genes, suggesting the propensity for sex steroids to directly affect dimorphic antiviral responses against Seoul virus infection.

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Figures

Figure 1
Figure 1
Numbers of genomic Seoul virus RNA copies (± SEM) in lung tissue collected 0, 1, 3, 15, 30, or 40 days after inoculation with Seoul virus from intact males (IM), adult gonadectomized males (AGM), neonatally gonadectomized males (NGM), intact females (IF), adult gonadectomized females (AGF), or neonatally gonadectomized females (NGF). * IM > IF, † IF > IM, ‡ IM > AGM and NGM, p < 0.05, two-way ANOVAs (A–C).
Figure 2
Figure 2
Numbers of genomic Seoul virus RNA copies (± SEM) shed in saliva collected 0, 1, 3, 15, 30, or 40 days after inoculation with Seoul virus from intact males (IM), adult gonadectomized males (AGM), neonatally gonadectomized males (NGM), intact females (IF), adult gonadectomized females (AGF), or neonatally gonadectomized females (NGF). * IM > IF, ‡ IM > AGM and NGM, † IF < AGF and/or NGF, p < 0.05, two-way ANOVAs.
Figure 3
Figure 3
Expression of TLR7 (A–C), TLR3 (D–F), and RIG-I (G–I) mRNA in the lungs of intact males (IM), adult gonadectomized males (AGM), neonatally gonadectomized males (NGM), intact females (IF), adult gonadectomized females (AGF), and neonatally gonadectomized females (NGF) collected 0, 1, 3, 15, 30, or 40 days after inoculation with Seoul virus. * IF > IM, # IM > IF, ‡ IM < AGM, § IM > AGM and NGM, † IF > AGF and NGF, p < 0.05, two-way ANOVAs.
Figure 4
Figure 4
Expression of IFNβ (A–C) and Mx2 (D–F) mRNA (± SEM) in the lungs of intact males (IM), adult gonadectomized males (AGM), neonatally gonadectomized males (NGM), intact females (IF), adult gonadectomized females (AGF), and neonatally gonadectomized females (NGF) collected 0, 1, 3, 15, 30, or 40 days after inoculation with Seoul virus. * IF > IM, ‡ IM < AGM and/or NGM, † IF > AGF and/or NGF, # IF < AGF, p < 0.05, two-way ANOVAs.
Figure 5
Figure 5
Mx protein production in lung tissues collected 0, 3, 15, or 40 days after inoculation with Seoul virus. Semiquantitative scoring (± SEM) of Seoul virus nucleocapsid protein (SEOV NP; A) and Mx protein (B) examined by IHC. Scores: 0 = no cells present; 1 = 1 cell/visual field; 2 = 2–3 cells/visual field; 3 = 4–10 cells/visual field; 4 = 10+ cells/visual field. Each data point represents the average score from 3 animals/time point and each individual score represents the mean cell count from 4 randomly selected visual fields. Colocalization of SEOV NP and Mx protein in the lungs of intact male (IM) and intact female (IF) rats collected 40 days p.i. (C). Western blot analyses of protein extracts from lung tissues collected 0, 3, 15, or 40 days p.i. or from uninfected rats injected with rIFNα (positive control [+]) incubated with antibody against human MxA, that cross-reacts with rat Mx2 and Mx3 (M143), or β actin (D); results are representative of 3 independent experiments. See Materials and Methods for additional details. * IM > IF, † IF > IM, p < 0.05, two-way ANOVAs (A–B).
Figure 6
Figure 6
TLR and RIG-I-mediated responses are upregulated in female rats during Seoul virus infection based on integration of microarray and real-time RT-PCR data analyses using GenMAPP 2.1 pathway analysis software, two-way ANOVAs, p < 0.05. Numbers to the right of each gene are fold-change expression in females relative to males during the acute phase of infection (Days 3–15 p.i.). Genes shaded pink are upregulated in females, genes colored blue are upregulated in males, genes shaded gray are not differentially expressed between the sexes, and genes that are white either have raw expression values < 200 units or are not arrayed on the RAE230A GeneChip (Affymetrix; see text for details).
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References

    1. Alff PJ, Gavrilovskaya IN, Gorbunova E, Endriss K, Chong Y, Geimonen E, Sen N, Reich NC, Mackow ER. The pathogenic NY-1 hantavirus G1 cytoplasmic tail inhibits RIG-I- and TBK-1-directed interferon responses. J Virol. 2006;80:9676–9686. - PMC - PubMed
    1. Allen LJ, McCormack RK, Jonsson CB. Mathematical models for hantavirus infection in rodents. Bull Math Biol. 2006;68:511–524. - PMC - PubMed
    1. Arnold AP, Breedlove SM. Organizational and activational effects of sex steroids on brain and behavior: a reanalysis. Horm Behav. 1985;19:469–498. - PubMed
    1. Botten J, Mirowsky K, Kusewitt D, Ye C, Gottlieb K, Prescott J, Hjelle B. Persistent Sin Nombre virus infection in the deer mouse (Peromyscus maniculatus) model: sites of replication and strand-specific expression. J Virol. 2003;77:1540–1550. - PMC - PubMed
    1. Brabin L. Interactions of the female hormonal environment, susceptibility to viral infections, and disease progression. AIDS Patient Care STDS. 2002;16:211–221. - PubMed

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