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Abstract
The deoxynucleoside triphosphate triphosphohydrolase and 3'-> 5' exonuclease SAMHD1 restricts HIV-1 infection in noncycling hematopoietic cells in vitro, and SAMHD1 mutations are associated with AGS. Little is known about the in vivo expression and functional regulation of this cellular factor. Here, we first assessed the SAMHD1 protein expression profile on a microarray of 25 human tissues from >210 donors and in purified primary cell populations. In vivo, SAMHD1 was expressed in the majority of nucleated cells of hematopoietic origin, including tissue-resident macrophages, DCs, pDCs, all developmental stages of thymic T cells, monocytes, NK cells, as well as at lower levels in B cells. Of note, SAMHD1 was abundantly expressed in HIV target cells residing in the anogenital mucosa, providing a basis for its evaluation as a cellular factor that may impact the efficiency of HIV transmission. Next, we examined the effect of the activation status and proinflammatory cytokine treatment of cells on expression and phosphorylation of SAMHD1. Activated, HIV-susceptible CD4(+) T cells carried pSAMHD1(T592), whereas resting CD4(+) T cells and macrophages expressed the unphosphorylated protein with HIV-restrictive activity. Surprisingly, stimulation of these primary cells with IFN-alpha, IFN-gamma, IL-4, IL-6, IL-12, IL-18, IL-27, or TNF-alpha affected neither SAMHD1 expression levels nor threonine 592 phosphorylation. Only IL-1 beta moderately down-regulated SAMHD1 in activated CD4(+) T cells. Taken together, this study establishes the first cross-sectional protein expression profile of SAMHD1 in human tissues and provides insight into its cell cycle-dependent phosphorylation and unresponsiveness to multiple proinflammatory cytokines.
Keywords
innate immunity, restriction factor, HIV, HSV, AICARDI-GOUTIERES-SYNDROME, RESTRICTION FACTOR SAMHD1, IMMUNODEFICIENCY-VIRUS TYPE-1, NUCLEIC-ACID METABOLISM, GAMMA-INDUCED PROTEIN, HIV-1 RESTRICTION, DENDRITIC CELLS, IN-VIVO, REPLICATION, INFECTION

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Citation

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MLA
Schmidt, Sarah et al. “SAMHD1’s Protein Expression Profile in Humans.” JOURNAL OF LEUKOCYTE BIOLOGY 98.1 (2015): 5–14. Print.
APA
Schmidt, S., Schenkova, K., Adam, T., Erikson, E., Lehmann-Koch, J., Sertel, S., Verhasselt, B., et al. (2015). SAMHD1’s protein expression profile in humans. JOURNAL OF LEUKOCYTE BIOLOGY, 98(1), 5–14.
Chicago author-date
Schmidt, Sarah, Kristina Schenkova, Tarek Adam, Elina Erikson, Judith Lehmann-Koch, Serkan Sertel, Bruno Verhasselt, Oliver T Fackler, Felix Lasitschka, and Oliver T Keppler. 2015. “SAMHD1’s Protein Expression Profile in Humans.” Journal of Leukocyte Biology 98 (1): 5–14.
Chicago author-date (all authors)
Schmidt, Sarah, Kristina Schenkova, Tarek Adam, Elina Erikson, Judith Lehmann-Koch, Serkan Sertel, Bruno Verhasselt, Oliver T Fackler, Felix Lasitschka, and Oliver T Keppler. 2015. “SAMHD1’s Protein Expression Profile in Humans.” Journal of Leukocyte Biology 98 (1): 5–14.
Vancouver
1.
Schmidt S, Schenkova K, Adam T, Erikson E, Lehmann-Koch J, Sertel S, et al. SAMHD1’s protein expression profile in humans. JOURNAL OF LEUKOCYTE BIOLOGY. 2015;98(1):5–14.
IEEE
[1]
S. Schmidt et al., “SAMHD1’s protein expression profile in humans,” JOURNAL OF LEUKOCYTE BIOLOGY, vol. 98, no. 1, pp. 5–14, 2015.
@article{6905573,
  abstract     = {The deoxynucleoside triphosphate triphosphohydrolase and 3'-> 5' exonuclease SAMHD1 restricts HIV-1 infection in noncycling hematopoietic cells in vitro, and SAMHD1 mutations are associated with AGS. Little is known about the in vivo expression and functional regulation of this cellular factor. Here, we first assessed the SAMHD1 protein expression profile on a microarray of 25 human tissues from >210 donors and in purified primary cell populations. In vivo, SAMHD1 was expressed in the majority of nucleated cells of hematopoietic origin, including tissue-resident macrophages, DCs, pDCs, all developmental stages of thymic T cells, monocytes, NK cells, as well as at lower levels in B cells. Of note, SAMHD1 was abundantly expressed in HIV target cells residing in the anogenital mucosa, providing a basis for its evaluation as a cellular factor that may impact the efficiency of HIV transmission. Next, we examined the effect of the activation status and proinflammatory cytokine treatment of cells on expression and phosphorylation of SAMHD1. Activated, HIV-susceptible CD4(+) T cells carried pSAMHD1(T592), whereas resting CD4(+) T cells and macrophages expressed the unphosphorylated protein with HIV-restrictive activity. Surprisingly, stimulation of these primary cells with IFN-alpha, IFN-gamma, IL-4, IL-6, IL-12, IL-18, IL-27, or TNF-alpha affected neither SAMHD1 expression levels nor threonine 592 phosphorylation. Only IL-1 beta moderately down-regulated SAMHD1 in activated CD4(+) T cells. Taken together, this study establishes the first cross-sectional protein expression profile of SAMHD1 in human tissues and provides insight into its cell cycle-dependent phosphorylation and unresponsiveness to multiple proinflammatory cytokines.},
  author       = {Schmidt, Sarah and Schenkova, Kristina and Adam, Tarek and Erikson, Elina and Lehmann-Koch, Judith and Sertel, Serkan and Verhasselt, Bruno and Fackler, Oliver T and Lasitschka, Felix and Keppler, Oliver T},
  issn         = {0741-5400},
  journal      = {JOURNAL OF LEUKOCYTE BIOLOGY},
  keywords     = {innate immunity,restriction factor,HIV,HSV,AICARDI-GOUTIERES-SYNDROME,RESTRICTION FACTOR SAMHD1,IMMUNODEFICIENCY-VIRUS TYPE-1,NUCLEIC-ACID METABOLISM,GAMMA-INDUCED PROTEIN,HIV-1 RESTRICTION,DENDRITIC CELLS,IN-VIVO,REPLICATION,INFECTION},
  language     = {eng},
  number       = {1},
  pages        = {5--14},
  title        = {SAMHD1's protein expression profile in humans},
  url          = {http://dx.doi.org/10.1189/jlb.4HI0714-338RR},
  volume       = {98},
  year         = {2015},
}

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