Substance P enhances HIV-1 infection in human fetal brain cell cultures expressing full-length neurokinin-1 receptor

Schwartz, Lynnae; Spitsin, Sergei; Meshki, John; Tuluc, Florin; Douglas, Steven D.; Wolfe, John H.

doi:10.1007/s13365-013-0166-x

Cited by 7 publications

(5 citation statements)

References 40 publications

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“…The inability to trigger NK-1R decreases bacterial clearance and increases death rates in mouse models of infection (Verdrengh and Tarkowski, 2008). SP and/or NK-1R have been linked to disease caused by infectious agents (Douglas et al, 2001; Schwartz et al, 2013), autoimmune disorders (Mantyh et al, 1988), psychological disturbances (Fehder et al, 1997; Herpfer and Lieb, 2005; McLean, 2005; Ebner and Singewald, 2006; Carpenter et al, 2008), cancer (Esteban et al, 2006), atopic dermatitis (Toyoda et al, 2002), and cell proliferation (Goode et al, 2003). EF-Tu from S. aureus, S. epidermidis , and B. cereus has been shown to bind SP, with an associated increase in virulence and biofilm formation (Mijouin et al, 2013; N’Diaye et al, 2016).…”

Section: Moonlighting Proteins In Bacteriamentioning

confidence: 99%

The Diverse Functional Roles of Elongation Factor Tu (EF-Tu) in Microbial Pathogenesis

Harvey

Jarocki

Charles³

et al. 2019

Front. Microbiol.

151

103

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Elongation factor thermal unstable Tu (EF-Tu) is a G protein that catalyzes the binding of aminoacyl-tRNA to the A-site of the ribosome inside living cells. Structural and biochemical studies have described the complex interactions needed to effect canonical function. However, EF-Tu has evolved the capacity to execute diverse functions on the extracellular surface of both eukaryote and prokaryote cells. EF-Tu can traffic to, and is retained on, cell surfaces where can interact with membrane receptors and with extracellular matrix on the surface of plant and animal cells. Our structural studies indicate that short linear motifs (SLiMs) in surface exposed, non-conserved regions of the molecule may play a key role in the moonlighting functions ascribed to this ancient, highly abundant protein. Here we explore the diverse moonlighting functions relating to pathogenesis of EF-Tu in bacteria and examine putative SLiMs on surface-exposed regions of the molecule.

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Section: Moonlighting Proteins In Bacteriamentioning

confidence: 99%

The Diverse Functional Roles of Elongation Factor Tu (EF-Tu) in Microbial Pathogenesis

Harvey

Jarocki

Charles³

et al. 2019

Front. Microbiol.

151

103

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“…Viral levels correlate with the amount of substance P released by immune cells and it has been suggested that this neuropeptide may facilitate viral replication by increasing the expression of receptors including CCR5 that are required for HIV infection of host cells (Bost, 2004a; Manak et al, 2010). In the CNS, human fetal brain cells have been shown to express NK-1R and interactions between this receptor and substance P appear to exacerbate HIV-1 infection (Schwartz et al, 2013). …”

Section: Evidence For the Involvement Of Substance P In Cns Disordersmentioning

confidence: 99%

The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders

Johnson

Young

Marriott

2017

Front. Cell. Neurosci.

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The inflammatory responses of resident central nervous system (CNS) cells are now known to play a critical role in the initiation and progression of an array of infectious and sterile neuroinflammatory disorders such as meningitis, encephalitis, Parkinson’s disease, Alzheimer’s disease and multiple sclerosis (MS). Regulating glial inflammatory responses in a timely manner is therefore critical in preserving normal CNS functions. The neuropeptide substance P is produced at high levels within the CNS and its selective receptor, the neurokinin 1 receptor (NK-1R), is abundantly expressed by neurons and is present on glial cell types including microglia and astrocytes. In addition to its functions as a neurotransmitter in the perception of pain and its essential role in gut motility, this tachykinin is widely recognized to exacerbate inflammation at peripheral sites including the skin, gastrointestinal tract and the lungs. Recently, a number of studies have identified a role for substance P and NK-1R interactions in neuroinflammation and described the ability of this neuropeptide to alter the immune functions of activated microglia and astrocytes. In this review article, we describe the expression of substance P and its receptor by resident CNS cells, and we discuss the ability of this neuropeptide to exacerbate the inflammatory responses of glia and immune cells that are recruited to the brain during neurodegenerative diseases. In addition, we discuss the available data indicating that the NK-1R-mediated augmentation of such responses appears to be detrimental during microbial infection and some sterile neurodegenerative disorders, and propose the repurposed use of NK-1R antagonists, of a type that are currently approved as anti-emetic and anti-anxiolytic agents, as an adjunct therapy to ameliorate the inflammatory CNS damage in these conditions.

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“…The effect of SP on viruses that cause neurocognitive impairment, such as human immunodeficiency virus (HIV) has also been investigated. An in vitro study using human fetal brain cell cultures expressing full-length NK1R showed that SP enhances HIV-1 infection 27 . Likewise, in vivo studies demonstrated that SP drives macrophage polarization and inflammation in HIV patients with neurocognitive impairment [28][29][30] .…”

Section: Neuroinflammation and Substance Pmentioning

confidence: 99%

Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

Martínez

Philipp

2016

J Neurol Neuromedicine

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This review addresses the role that substance P (SP) and its preferred receptor neurokinin-1 (NK1R) play in neuroinflammation associated with select bacterial, viral, parasitic, and neurodegenerative diseases of the central nervous system. The SP/NK1R complex is a key player in the interaction between the immune and nervous systems. A common effect of this interaction is inflammation. For this reason and because of the predominance in the human brain of the NK1R, its antagonists are attractive potential therapeutic agents. Preventing the deleterious effects of SP through the use of NK1R antagonists has been shown to be a promising therapeutic strategy, as these antagonists are selective, potent, and safe. Here we evaluate their utility in the treatment of different neuroinfectious and neuroinflammatory diseases, as a novel approach to clinical management of CNS inflammation.

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Substance P enhances HIV-1 infection in human fetal brain cell cultures expressing full-length neurokinin-1 receptor

Cited by 7 publications

References 40 publications

The Diverse Functional Roles of Elongation Factor Tu (EF-Tu) in Microbial Pathogenesis

The Diverse Functional Roles of Elongation Factor Tu (EF-Tu) in Microbial Pathogenesis

The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders

Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

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