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

The associations between the neurokinin-1 receptor (NK-1R), substance P (SP), and HIV-1 were investigated in neurosphere-derived cultures of microglial-depleted human fetal brain cells (HFBC). Full-length NK-1R was identified in HFBC cultures. SP treatment of the HFBC increased intracellular calcium mobilization and decreased electrical impedance, both of which were blocked by the NK-1R antagonist aprepitant.

Substance P inhibits natural killer cell cytotoxicity through the neurokinin-1 receptor.

SP is a potent neuroimmunomodulator that functions through ligating members of the neurokinin receptor family, one of which, NK1R, is widely expressed in immune cells. As in humans, circulating SP levels are increased in pathologic states associated with impairment of NK cell functions, such as depression and HIV infection, we hypothesized that SP has a direct, inhibitory effect upon NK cells. We have studied a clonal human NK cell line (YTS) as well as ex vivo human NK cells and have determined that truncated and full-length NK1R isoforms are expressed in and SP bound by ex vivo NK cells and the YTS NK cell line.

Prevalence of pain and association with psychiatric symptom severity in perinatally HIV-infected children as compared to controls living in HIV-affected households.

This cross-sectional study evaluated the prevalence of pain and psychiatric symptoms in perinatally HIV-infected children at entry into P1055, a multicenter investigation of the prevalence and severity of psychiatric symptoms in HIV-infected children. Subjects 6-17 years of age and their primary caregivers were recruited from 29 International Maternal Pediatric Adolescent AIDS Clinical Trials sites in the USA and Puerto Rico. A total of 576 children (320 HIV and 256 HIV- children) were enrolled from June 2005 to September 2006.

Neurokinin 1 receptor mediates membrane blebbing in HEK293 cells through a Rho/Rho-associated coiled-coil kinase-dependent mechanism.

We have investigated the effect of neurokinin 1 receptor (NK1R) agonists on HEK293 cells transfected with the NK1R receptor. The NK1R receptor mediates dramatic shape changes that include contractions of the membrane cortex resulting in membrane bleb formation. We have found that the cell shape changes correlate with changes in electrical impedance measured in cellular monolayers.

Neurokinin-1 receptor expression and function in human macrophages and brain: perspective on the role in HIV neuropathogenesis.

Substance P (SP) is upregulated in HIV infection in adult men and women, as determined by increased plasma levels. There is a reciprocal and bidirectional relationship between substance P and HIV in HIV-infected monocyte-derived macrophages and cell lines (e.g.

Substance P (SP) enhances CCL5-induced chemotaxis and intracellular signaling in human monocytes, which express the truncated neurokinin-1 receptor (NK1R).

Substance P (SP) is a potent modulator of monocyte/macrophage function. The SP-preferring receptor neurokinin-1 receptor (NK1R) has two forms: a full-length NK1R (NK1R-F) isoform and a truncated NK1R (NK1R-T) isoform, which lacks the terminal cytoplasmic 96-aa residues. The distribution of these receptor isoforms in human monocytes is not known.

Evidence of human immunodeficiency virus type 1 infection of nestin-positive neural progenitors in archival pediatric brain tissue.

Human immunodeficiency virus type 1 (HIV-1) central nervous system (CNS) infection in children is associated with impaired brain growth and neurodevelopmental delays. Neural progenitors are critical for neurogenesis. Human multipotential neural progenitors grown in culture are permissive for HIV-1 infection, but it is not known if infection of these cells occurs in vivo.

Neural progenitors and HIV-1-associated central nervous system disease in adults and children.

The human immunodeficiency virus type 1 (HIV-1) is a neurotrophic lentivirus that enters and infects the central nervous system (CNS) of adults and children, giving rise to the clinical syndromes of AIDS-dementia complex (ADC) in adults and HIV-1-associated progressive encephalopathy (PE) in pediatric patients. The clinical presentation and progression of neuroAIDS in the developing brain of children is distinct from that seen in adult patients. Neuroimaging, and upon autopsy, neuropathological findings corresponding to clinical disease in pediatric patients include impaired brain growth, reactive gliosis, myelin pallor, calcifications of the basal ganglia, cortical and cerebral atrophy with neuronal loss and ventricular enlargement, and abnormalities of cerebral vasculature.

Human immunodeficiency virus type 1 infection of human brain-derived progenitor cells.

Although cells of monocytic lineage are the primary source of human immunodeficiency virus type 1 (HIV-1) in the brain, other cell types in the central nervous system, including astrocytes, can harbor a latent or persistent HIV-1 infection. In the present study, we examined whether immature, multipotential human brain-derived progenitor cells (nestin positive) are also permissive for infection. When exposed to IIIB and NL4-3 strains of HIV-1, progenitor cells and progenitor-derived astrocytes became infected, with peak p24 levels of 100 to 500 pg/ml at 3 to 6 days postinfection.