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 language | English (US) |
|---|---|
| Pages (from-to) | 491-503 |
| Number of pages | 13 |
| Journal | Critical reviews in immunology |
| Volume | 38 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jan 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - The TRAIL
T2 - TRAILshort Axis in HIV Immunopathology
AU - Aboulnasr, Fatma
AU - Paranjape, Geeta
AU - Badley, Andrew David
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85065102088&partnerID=8YFLogxK
U2 - 10.1615/CritRevImmunol.2019029632
DO - 10.1615/CritRevImmunol.2019029632
M3 - Article
C2 - 31002603
AN - SCOPUS:85065102088
VL - 38
SP - 491
EP - 503
JO - Critical Reviews in Immunology
JF - Critical Reviews in Immunology
SN - 1040-8401
IS - 6
ER -