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Virion encapsidated HIV-1 Vpr induces NFAT to prime non-activated T cells for productive infection

(2016) OPEN BIOLOGY. 6(7).
Author
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Abstract
The majority of T cells encountered by HIV-1 are non-activated and do not readily allow productive infection. HIV-1 Vpr is highly abundant in progeny virions, and induces signalling and HIV-1 LTR transcription. We hence hypothesized that Vpr might be a determinant of non-activated T-cell infection. Virion-delivered Vpr activated nuclear factor of activated T cells (NFAT) through Ca2+ influx and interference with the NFAT export kinase GSK3β. This leads to NFAT translocation and accumulation within the nucleus and was required for productive infection of unstimulated primary CD4+ T cells. A mutagenesis approach revealed correlation of Vpr-mediated NFAT activation with its ability to enhance LTR transcription and mediate cell cycle arrest. Upon NFAT inhibition, Vpr did not augment resting T-cell infection, and showed reduced G2/M arrest and LTR transactivation. Altogether, Vpr renders unstimulated T cells more permissive for productive HIV-1 infection and stimulates activation of productively infected as well as virus-exposed T cells. Therefore, it could be involved in the establishment and reactivation of HIV-1 from viral reservoirs and might have an impact on the levels of immune activation, which are determinants of HIV-1 pathogenesis.
Keywords
T cells, HIV-1, Vpr, LTR transcription, NFAT, cell cycle arrest, IMMUNODEFICIENCY-VIRUS TYPE-1, HUMAN LYMPHOID-TISSUE, EX-VIVO, TRANSCRIPTION FACTOR, GENE-EXPRESSION, NUCLEAR-FACTOR, KAPPA-B, MACROPHAGE INFECTION, ACCESSORY PROTEINS, IMMUNE ACTIVATION

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Citation

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MLA
Höhne, Kristin et al. “Virion Encapsidated HIV-1 Vpr Induces NFAT to Prime Non-activated T Cells for Productive Infection.” OPEN BIOLOGY 6.7 (2016): n. pag. Print.
APA
Höhne, K., Businger, R., Van Nuffel, A., Bolduan, S., Koppensteiner, H., Baeyens, A., VERMEIRE, J., et al. (2016). Virion encapsidated HIV-1 Vpr induces NFAT to prime non-activated T cells for productive infection. OPEN BIOLOGY, 6(7).
Chicago author-date
Höhne, Kristin, Ramona Businger, Anouk Van Nuffel, Sebastian Bolduan, Herwig Koppensteiner, Ann Baeyens, JOLIEN VERMEIRE, Eva Malatinková, Bruno Verhasselt, and Michael Schindler. 2016. “Virion Encapsidated HIV-1 Vpr Induces NFAT to Prime Non-activated T Cells for Productive Infection.” Open Biology 6 (7).
Chicago author-date (all authors)
Höhne, Kristin, Ramona Businger, Anouk Van Nuffel, Sebastian Bolduan, Herwig Koppensteiner, Ann Baeyens, JOLIEN VERMEIRE, Eva Malatinková, Bruno Verhasselt, and Michael Schindler. 2016. “Virion Encapsidated HIV-1 Vpr Induces NFAT to Prime Non-activated T Cells for Productive Infection.” Open Biology 6 (7).
Vancouver
1.
Höhne K, Businger R, Van Nuffel A, Bolduan S, Koppensteiner H, Baeyens A, et al. Virion encapsidated HIV-1 Vpr induces NFAT to prime non-activated T cells for productive infection. OPEN BIOLOGY. 2016;6(7).
IEEE
[1]
K. Höhne et al., “Virion encapsidated HIV-1 Vpr induces NFAT to prime non-activated T cells for productive infection,” OPEN BIOLOGY, vol. 6, no. 7, 2016.
@article{8060358,
  abstract     = {The majority of T cells encountered by HIV-1 are non-activated and do not readily allow productive infection. HIV-1 Vpr is highly abundant in progeny virions, and induces signalling and HIV-1 LTR transcription. We hence hypothesized that Vpr might be a determinant of non-activated T-cell infection. Virion-delivered Vpr activated nuclear factor of activated T cells (NFAT) through Ca2+ influx and interference with the NFAT export kinase GSK3β. This leads to NFAT translocation and accumulation within the nucleus and was required for productive infection of unstimulated primary CD4+ T cells. A mutagenesis approach revealed correlation of Vpr-mediated NFAT activation with its ability to enhance LTR transcription and mediate cell cycle arrest. Upon NFAT inhibition, Vpr did not augment resting T-cell infection, and showed reduced G2/M arrest and LTR transactivation. Altogether, Vpr renders unstimulated T cells more permissive for productive HIV-1 infection and stimulates activation of productively infected as well as virus-exposed T cells. Therefore, it could be involved in the establishment and reactivation of HIV-1 from viral reservoirs and might have an impact on the levels of immune activation, which are determinants of HIV-1 pathogenesis.},
  articleno    = {160046},
  author       = {Höhne, Kristin and Businger, Ramona and Van Nuffel, Anouk and Bolduan, Sebastian and Koppensteiner, Herwig and Baeyens, Ann and VERMEIRE, JOLIEN and Malatinková, Eva and Verhasselt, Bruno and Schindler, Michael},
  issn         = {2046-2441},
  journal      = {OPEN BIOLOGY},
  keywords     = {T cells,HIV-1,Vpr,LTR transcription,NFAT,cell cycle arrest,IMMUNODEFICIENCY-VIRUS TYPE-1,HUMAN LYMPHOID-TISSUE,EX-VIVO,TRANSCRIPTION FACTOR,GENE-EXPRESSION,NUCLEAR-FACTOR,KAPPA-B,MACROPHAGE INFECTION,ACCESSORY PROTEINS,IMMUNE ACTIVATION},
  language     = {eng},
  number       = {7},
  pages        = {17},
  title        = {Virion encapsidated HIV-1 Vpr induces NFAT to prime non-activated T cells for productive infection},
  url          = {http://dx.doi.org/10.1098/rsob.160046},
  volume       = {6},
  year         = {2016},
}

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