Substantial induction of non-apoptotic CD4 T-cell death during the early phase of HIV-1 infection in a humanized mouse model

Microbes Infect. 2021 Jan-Feb;23(1):104767. doi: 10.1016/j.micinf.2020.10.003. Epub 2020 Oct 10.

Abstract

Several mechanisms underline induction of CD4 T-cell death by human immunodeficiency virus (HIV) infection. For a long time, apoptosis was considered central to cell death involved in the depletion of CD4 T cells during HIV infection. However, which types of cell death are induced during the early phase of HIV infection in vivo remains unclear. In this study, CD4 T-cell death induced in early HIV infection was characterized using humanized mice challenged with CCR5-tropic (R5) or CXCR4-tropic (X4) HIV-1. Results showed that CD4 T-cell death was induced in the spleen 3 days post-challenge with both R5 and X4 HIV-1. Although cell death without caspase-1 and caspase-3/7 activation was preferentially observed, caspase-1+ pyroptosis was also significantly induced within the memory subpopulation by R5 or X4 HIV-1 and the naïve subpopulation by X4 HIV-1. In contrast, caspase-3/7+ apoptosis was not enhanced by either R5 or X4 HIV-1. Furthermore, phosphorylated mixed lineage kinase domain-like protein+ necroptosis was induced by only X4 HIV-1. These findings indicate that various types of non-apoptotic CD4 T-cell death, such as pyroptosis and necroptosis, are induced during the early phase of HIV infection in vivo.

Keywords: Apoptosis; CD4 T cells; HIV; Humanized mice; Necroptosis; Pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 7 / genetics
  • Caspase 7 / metabolism
  • Cell Death*
  • Disease Models, Animal
  • HIV Infections / genetics
  • HIV Infections / metabolism
  • HIV Infections / physiopathology*
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Mice

Substances

  • Caspase 3
  • Caspase 7