The TRAIL: TRAILshort Axis in HIV Immunopathology

Fatma Aboulnasr, Geeta Paranjape, Andrew David Badley

Research output: Contribution to journalArticle

Abstract

Accelerated loss of HIV-infected and uninfected CD4 T cells is a hallmark of HIV infection that leads to severe immunodeficiency, rendering the host susceptible to opportunistic infections and malignancies. Obstacles to eradicating HIV involve the virus's ability to remain in a quiescent state as latent viral reservoirs and manipulate host defenses to benefit viral survival and persistence of the infected reservoir. Several mechanisms cause CD4 T-cell depletion and recent studies demonstrate the role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in this process. Expression of TRAIL and its receptors is upregulated in response to HIV infection. TRAIL interacts with its receptors to activate apoptotic pathways. We recently demonstrated the presence of TRAILshort, a novel splice variant of full-length TRAIL, in the serum of HIV-infected patients. A unique carboxy-terminus allows TRAILshort to bind to death receptors without inducing apoptosis and prevents TRAIL from binding to its receptors, thereby conferring resistance to TRAIL-mediated death. In this review, we describe how the TRAIL: TRAILshort receptor axis modulates apoptosis of different types of immune cells in the context of HIV infection. We also discuss how TRAIL and TRAILshort contribute to the activation of immune cells involved in host defense against HIV and mechanisms that HIV has evolved to manipulate TRAIL for its survival.

Original languageEnglish (US)
Pages (from-to)491-503
Number of pages13
JournalCritical reviews in immunology
Volume38
Issue number6
DOIs
StatePublished - Jan 1 2018

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HIV
TNF-Related Apoptosis-Inducing Ligand Receptors
HIV Infections
Apoptosis
T-Lymphocytes
Death Domain Receptors
Survival
Opportunistic Infections
Tumor Necrosis Factor-alpha
Ligands
Viruses
Serum
Neoplasms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The TRAIL : TRAILshort Axis in HIV Immunopathology. / Aboulnasr, Fatma; Paranjape, Geeta; Badley, Andrew David.

In: Critical reviews in immunology, Vol. 38, No. 6, 01.01.2018, p. 491-503.

Research output: Contribution to journalArticle

Aboulnasr, Fatma ; Paranjape, Geeta ; Badley, Andrew David. / The TRAIL : TRAILshort Axis in HIV Immunopathology. In: Critical reviews in immunology. 2018 ; Vol. 38, No. 6. pp. 491-503.
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