Related Experiment Video

Updated: Aug 15, 2026

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

The pro-apoptotic human BH3-only peptide harakiri is expressed in cryptococcus-infected perivascular macrophages in

Takashi Shinoe1, Akio Wanaka, Takuya Nikaido

  • 1Department of Neurology, Division of Neuroscience, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan. tshinoe-tky@umin.ac.jp

Neuroscience Letters
|October 19, 2005
PubMed

Insights

The pro-apoptotic protein harakiri (Hrk) is expressed in macrophages within the central nervous system (CNS) of AIDS patients. This suggests Hrk may play a role in eliminating HIV-1 and opportunistic infections in the brain.

Area of Science:

  • Neuroscience
  • Immunology
  • Virology

Background:

  • Human Immunodeficiency Virus type 1 (HIV-1) primarily infects microglia/macrophages in the central nervous system (CNS).
  • Apoptosis (programmed cell death) is implicated in the elimination of infected macrophages and contributes to neuropathology in Acquired Immunodeficiency Syndrome (AIDS).

Purpose of the Study:

  • To investigate the expression of the pro-apoptotic BH3-peptide harakiri (Hrk) in brain tissues of AIDS patients.
  • To determine the cellular localization and association of Hrk expression with HIV-1 and opportunistic infections in the CNS.

Main Methods:

  • Immunohistochemistry was used to detect Hrk expression in brain tissues.
  • Grocott's methenamine silver staining identified fungal elements.
  • Confocal laser microscopy visualized co-localization of Hrk with HIV-1 and Cryptococcus neoformans.
  • In situ hybridization confirmed Hrk messenger RNA (mRNA) expression within macrophages.

Main Results:

  • Hrk immunoreactivity was observed in perivascular macrophages within specific brain lesions.
  • Many Hrk-positive macrophages contained inclusions indicative of opportunistic infections, such as Cryptococcus neoformans.
  • Hrk expression was found to co-localize with both HIV-1 and Cryptococcus neoformans.
  • In situ hybridization confirmed that Hrk mRNA was present in these macrophages, ruling out phagocytosis of the protein.

Conclusions:

  • The pro-apoptotic protein Hrk is expressed in macrophages within the CNS of AIDS patients, particularly in areas with opportunistic infections.
  • Hrk expression in these macrophages suggests a role in the host's immune response, potentially contributing to the elimination of HIV-1 and co-infections.
  • Pro-apoptotic members of the BCL-2 family, including Hrk, may be involved in the delayed hypersensitivity reactions observed in AIDS patients during the clearance of opportunistic pathogens.

More Related Videos

Peptide-based Identification of Functional Motifs and their Binding Partners14:28

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

Related Concept Videos

Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Cryptococcal Meningitis01:27

Cryptococcal Meningitis

Cryptococcal meningitis is a life-threatening opportunistic infection predominantly associated with HIV/AIDS, accounting for over 100,000 deaths annually worldwide. However, it also affects individuals with other forms of immunosuppression, including those undergoing immunosuppressive therapy, organ transplant recipients, patients with innate immunodeficiencies, and individuals with hematological disorders. The infection is caused mainly by Cryptococcus neoformans and Cryptococcus gattii,...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...