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Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice
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| Zeitschriftentitel: | Journal of Virology |
|---|---|
| Personen und Körperschaften: | , |
| In: | Journal of Virology, 86, 2012, 6, S. 3327-3336 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
|
| Schlagwörter: |
| author_facet |
Long, Brian R. Stoddart, Cheryl A. Long, Brian R. Stoddart, Cheryl A. |
|---|---|
| author |
Long, Brian R. Stoddart, Cheryl A. |
| spellingShingle |
Long, Brian R. Stoddart, Cheryl A. Journal of Virology Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice Virology Insect Science Immunology Microbiology |
| author_sort |
long, brian r. |
| spelling |
Long, Brian R. Stoddart, Cheryl A. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.06676-11 <jats:title>ABSTRACT</jats:title> <jats:p> The development of small animal models for the study of HIV transmission is important for evaluation of HIV prophylaxis and disease pathogenesis. In humanized bone marrow-liver-thymus (BLT) mice, hematopoiesis is reconstituted by implantation of human fetal liver and thymus tissue (Thy/Liv) plus intravenous injection of autologous liver-derived hematopoietic stem progenitor cells (HSPC). This results in reconstitution of human leukocytes in the mouse peripheral blood, lymphoid organs, and mucosal sites. NOD- <jats:italic>scid</jats:italic> interleukin-2 receptor-negative (IL-2Rγ <jats:sup>−/−</jats:sup> ) (NSG)-BLT mice were inoculated intravaginally with HIV and were monitored for plasma viremia by a branched DNA assay 4 weeks later. T-cell activation was determined by expression of CD38 and HLA-DR on human CD4 <jats:sup>+</jats:sup> and CD8 <jats:sup>+</jats:sup> T cells in mouse peripheral blood at the time of inoculation and 4 weeks later. Additional BLT mice were treated with human alpha interferon 2b (IFN-α2b) (intron A) and assessed for T-cell activation. Productive HIV infection in BLT mice was associated with T-cell activation (increases in CD38 mean fluorescence intensity and both the frequency and absolute number of CD38 <jats:sup>+</jats:sup> HLA-DR <jats:sup>+</jats:sup> T cells) that correlated strongly with plasma viral load and was most pronounced in the CD8 <jats:sup>+</jats:sup> T-cell compartment. This T-cell activation phenotype was recapitulated in NSG-BLT mice treated with intron A. HIV susceptibility correlated with the number of HSPC injected, yet a number of mice receiving the Thy/Liv implant alone, with no HSPC injection, were also susceptible to intravaginal HIV. These results are consistent with studies linking T-cell activation to progressive disease in humans and lend support for the use of NSG-BLT mice in studies of HIV pathogenesis. </jats:p> Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice Journal of Virology |
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| title |
Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_unstemmed |
Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_full |
Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_fullStr |
Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_full_unstemmed |
Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_short |
Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_sort |
alpha interferon and hiv infection cause activation of human t cells in nsg-blt mice |
| topic |
Virology Insect Science Immunology Microbiology |
| url |
http://dx.doi.org/10.1128/jvi.06676-11 |
| publishDate |
2012 |
| physical |
3327-3336 |
| description |
<jats:title>ABSTRACT</jats:title>
<jats:p>
The development of small animal models for the study of HIV transmission is important for evaluation of HIV prophylaxis and disease pathogenesis. In humanized bone marrow-liver-thymus (BLT) mice, hematopoiesis is reconstituted by implantation of human fetal liver and thymus tissue (Thy/Liv) plus intravenous injection of autologous liver-derived hematopoietic stem progenitor cells (HSPC). This results in reconstitution of human leukocytes in the mouse peripheral blood, lymphoid organs, and mucosal sites. NOD-
<jats:italic>scid</jats:italic>
interleukin-2 receptor-negative (IL-2Rγ
<jats:sup>−/−</jats:sup>
) (NSG)-BLT mice were inoculated intravaginally with HIV and were monitored for plasma viremia by a branched DNA assay 4 weeks later. T-cell activation was determined by expression of CD38 and HLA-DR on human CD4
<jats:sup>+</jats:sup>
and CD8
<jats:sup>+</jats:sup>
T cells in mouse peripheral blood at the time of inoculation and 4 weeks later. Additional BLT mice were treated with human alpha interferon 2b (IFN-α2b) (intron A) and assessed for T-cell activation. Productive HIV infection in BLT mice was associated with T-cell activation (increases in CD38 mean fluorescence intensity and both the frequency and absolute number of CD38
<jats:sup>+</jats:sup>
HLA-DR
<jats:sup>+</jats:sup>
T cells) that correlated strongly with plasma viral load and was most pronounced in the CD8
<jats:sup>+</jats:sup>
T-cell compartment. This T-cell activation phenotype was recapitulated in NSG-BLT mice treated with intron A. HIV susceptibility correlated with the number of HSPC injected, yet a number of mice receiving the Thy/Liv implant alone, with no HSPC injection, were also susceptible to intravaginal HIV. These results are consistent with studies linking T-cell activation to progressive disease in humans and lend support for the use of NSG-BLT mice in studies of HIV pathogenesis.
</jats:p> |
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| description | <jats:title>ABSTRACT</jats:title> <jats:p> The development of small animal models for the study of HIV transmission is important for evaluation of HIV prophylaxis and disease pathogenesis. In humanized bone marrow-liver-thymus (BLT) mice, hematopoiesis is reconstituted by implantation of human fetal liver and thymus tissue (Thy/Liv) plus intravenous injection of autologous liver-derived hematopoietic stem progenitor cells (HSPC). This results in reconstitution of human leukocytes in the mouse peripheral blood, lymphoid organs, and mucosal sites. NOD- <jats:italic>scid</jats:italic> interleukin-2 receptor-negative (IL-2Rγ <jats:sup>−/−</jats:sup> ) (NSG)-BLT mice were inoculated intravaginally with HIV and were monitored for plasma viremia by a branched DNA assay 4 weeks later. T-cell activation was determined by expression of CD38 and HLA-DR on human CD4 <jats:sup>+</jats:sup> and CD8 <jats:sup>+</jats:sup> T cells in mouse peripheral blood at the time of inoculation and 4 weeks later. Additional BLT mice were treated with human alpha interferon 2b (IFN-α2b) (intron A) and assessed for T-cell activation. Productive HIV infection in BLT mice was associated with T-cell activation (increases in CD38 mean fluorescence intensity and both the frequency and absolute number of CD38 <jats:sup>+</jats:sup> HLA-DR <jats:sup>+</jats:sup> T cells) that correlated strongly with plasma viral load and was most pronounced in the CD8 <jats:sup>+</jats:sup> T-cell compartment. This T-cell activation phenotype was recapitulated in NSG-BLT mice treated with intron A. HIV susceptibility correlated with the number of HSPC injected, yet a number of mice receiving the Thy/Liv implant alone, with no HSPC injection, were also susceptible to intravaginal HIV. These results are consistent with studies linking T-cell activation to progressive disease in humans and lend support for the use of NSG-BLT mice in studies of HIV pathogenesis. </jats:p> |
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| spelling | Long, Brian R. Stoddart, Cheryl A. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.06676-11 <jats:title>ABSTRACT</jats:title> <jats:p> The development of small animal models for the study of HIV transmission is important for evaluation of HIV prophylaxis and disease pathogenesis. In humanized bone marrow-liver-thymus (BLT) mice, hematopoiesis is reconstituted by implantation of human fetal liver and thymus tissue (Thy/Liv) plus intravenous injection of autologous liver-derived hematopoietic stem progenitor cells (HSPC). This results in reconstitution of human leukocytes in the mouse peripheral blood, lymphoid organs, and mucosal sites. NOD- <jats:italic>scid</jats:italic> interleukin-2 receptor-negative (IL-2Rγ <jats:sup>−/−</jats:sup> ) (NSG)-BLT mice were inoculated intravaginally with HIV and were monitored for plasma viremia by a branched DNA assay 4 weeks later. T-cell activation was determined by expression of CD38 and HLA-DR on human CD4 <jats:sup>+</jats:sup> and CD8 <jats:sup>+</jats:sup> T cells in mouse peripheral blood at the time of inoculation and 4 weeks later. Additional BLT mice were treated with human alpha interferon 2b (IFN-α2b) (intron A) and assessed for T-cell activation. Productive HIV infection in BLT mice was associated with T-cell activation (increases in CD38 mean fluorescence intensity and both the frequency and absolute number of CD38 <jats:sup>+</jats:sup> HLA-DR <jats:sup>+</jats:sup> T cells) that correlated strongly with plasma viral load and was most pronounced in the CD8 <jats:sup>+</jats:sup> T-cell compartment. This T-cell activation phenotype was recapitulated in NSG-BLT mice treated with intron A. HIV susceptibility correlated with the number of HSPC injected, yet a number of mice receiving the Thy/Liv implant alone, with no HSPC injection, were also susceptible to intravaginal HIV. These results are consistent with studies linking T-cell activation to progressive disease in humans and lend support for the use of NSG-BLT mice in studies of HIV pathogenesis. </jats:p> Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice Journal of Virology |
| spellingShingle | Long, Brian R., Stoddart, Cheryl A., Journal of Virology, Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice, Virology, Insect Science, Immunology, Microbiology |
| title | Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_full | Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_fullStr | Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_full_unstemmed | Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_short | Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| title_sort | alpha interferon and hiv infection cause activation of human t cells in nsg-blt mice |
| title_unstemmed | Alpha Interferon and HIV Infection Cause Activation of Human T Cells in NSG-BLT Mice |
| topic | Virology, Insect Science, Immunology, Microbiology |
| url | http://dx.doi.org/10.1128/jvi.06676-11 |