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Pathogenesis and Immunity

Lymphocyte and Antibody Responses Reduce Enterovirus 71 Lethality in Mice by Decreasing Tissue Viral Loads

Yu-Wen Lin, Kung-Chao Chang, Chia-Min Kao, Shih-Ping Chang, Yuk-Ying Tung, Shun-Hua Chen
Yu-Wen Lin
1Institute of Biomedical Sciences
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Kung-Chao Chang
2Department of Pathology
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Chia-Min Kao
3Department of Microbiology and Immunology, College of Medicine
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Shih-Ping Chang
3Department of Microbiology and Immunology, College of Medicine
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Yuk-Ying Tung
4Statistical Analysis Laboratory, Institute of Education, College of Social Sciences, National Cheng Kung University, Tainan, Taiwan 701, Republic of China
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Shun-Hua Chen
1Institute of Biomedical Sciences
3Department of Microbiology and Immunology, College of Medicine
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  • For correspondence: shunhua@mail.ncku.edu.tw
DOI: 10.1128/JVI.00434-09
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  • FIG. 1.
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    FIG. 1.

    Presence of virus and lymphocytes in the spinal cord of an EV71-infected patient who died. Sections of the spinal cord specimen from a patient who died were stained with antibody against the EV71 capsid protein, VP1 (A) or human leukocyte antigen, CD20 (C), CD4 (D), or CD8 (E), or hematoxylin and eosin (H&E) (B). The reddish brown color in panel A and panels C to E denotes a positive reaction (original magnification, ×1,000 for panel A and ×400 for panels B to E).

  • FIG. 2.
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    FIG. 2.

    Kinetics of viral replication and lymphocyte infiltration in the brains of EV71-infected mice. (A) The survival of EV71-infected ICR mice (n = 20) is shown. (B) The viral titers in the brains of EV71-infected mice at the indicated times after infection are shown. The data shown are the mean values ± SE values (error bars) for six samples per time point. (C) The numbers of CD4+ T, CD8+ T, and CD19+ B cells in the brains of mock-infected or EV71-infected mice at the indicated times after infection are shown. The data shown are the mean values ± SE values (error bars) from three experiments.

  • FIG. 3.
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    FIG. 3.

    Lymphocytes reduce the lethality of EV71-infected mice by decreasing viral loads in tissues. The disease scores (A) and survival rates (B) of EV71-infected wild-type mice (black squares; n = 12) or mice deficient in CD4 T cells (white triangles; n = 9), CD8 T cells (white circles; n = 7), or B cells (white squares; n = 7) are shown. Disease scores that are significantly different by the Wilcoxon test are indicated as follows: †, P < 0.05; ††, P < 0.01. Survival rates that are significantly different by the log-rank test are indicated as follows: *, P < 0.05; ***, P < 0.001. (C) The viral titers in the indicated tissues of wild-type mice (WT; n = 6) or mice deficient in B cells (B−/−; n = 6), CD4 T cells (CD4−/−; n = 6), or CD8 T cells (CD8−/−; n = 10) 5 days after infection are shown. The data shown are the mean values plus SE values (error bars). Viral titers that are significantly different from those of wild-type mice by the Mann-Whitney U test are indicated as follows: §, P < 0.05; §§, P < 0.01.

  • FIG. 4.
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    FIG. 4.

    Production of EV71-specific antibodies with neutralizing activity. The neutralizing antibody titers in the sera of mock-infected or EV71-infected C57BL/6 mice collected 7 days after infection were determined by neutralization assay. The highest dilution of serum that protected RD cell monolayers from infection was taken as the neutralizing titer. Each symbol on the scatter gram represents an individual sample, and the black horizontal line represents the mean value for the EV71-infected mice.

  • FIG. 5.
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    FIG. 5.

    EV71-specific antibody reduces the lethality of infected mice by decreasing viral loads in tissues. The disease scores (A) and survival rates (B) of EV71-infected, B-cell-deficient mice given control antibody (n = 6) or EV71-specific antibody (n = 6) are shown. Disease scores that are significantly different (P < 0.001) by the Wilcoxon test are indicated (†††). Survival rates that are significantly different (P < 0.01) by the log-rank test are indicated (**). (C) The viral titers in the indicated tissues of infected, B-cell-deficient mice given control antibody (n = 6) or EV71-specific antibody (n = 6) 5 days after infection are shown. The data shown are the mean values plus SE values (error bars). Viral titers that are significantly different (P < 0.01) by the Mann-Whitney U test are indicated (§§).

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Lymphocyte and Antibody Responses Reduce Enterovirus 71 Lethality in Mice by Decreasing Tissue Viral Loads
Yu-Wen Lin, Kung-Chao Chang, Chia-Min Kao, Shih-Ping Chang, Yuk-Ying Tung, Shun-Hua Chen
Journal of Virology Jun 2009, 83 (13) 6477-6483; DOI: 10.1128/JVI.00434-09

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Lymphocyte and Antibody Responses Reduce Enterovirus 71 Lethality in Mice by Decreasing Tissue Viral Loads
Yu-Wen Lin, Kung-Chao Chang, Chia-Min Kao, Shih-Ping Chang, Yuk-Ying Tung, Shun-Hua Chen
Journal of Virology Jun 2009, 83 (13) 6477-6483; DOI: 10.1128/JVI.00434-09
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KEYWORDS

Antibodies, Viral
B-Lymphocytes
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Enterovirus A, Human
Viral Load

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