Methamphetamine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells
Department of Immunology, College of Medicine, Florida International University, Miami, FL 33155, USA. Journal of Neuroimmune Pharmacology
(Impact Factor: 4.11).
11/2008; 4(1):129-39. DOI: 10.1007/s11481-008-9128-0
The US is currently experiencing an epidemic of methamphetamine (Meth) use as a recreational drug. Recent studies also show a high prevalence of HIV-1 infection among Meth users. We report that Meth enhances HIV-1 infectivity of dendritic cells as measured by multinuclear activation of a galactosidase indicator (MAGI) cell assay, p24 assay, and LTR-RU5 amplification. Meth induces increased HIV-1 infection in association with an increase in the HIV-1 coreceptors, CXCR4 and CCR5, and infection is mediated by downregulation of extracellular-regulated kinase (ERK2) and the upregulation of p38 mitogen-activated protein kinase (MAPK). A p38 inhibitor (SB203580) specifically reversed the Meth-induced upregulation of the CCR5 HIV-1 coreceptor. The dopamine D2 receptor antagonist RS +/- sulpiride significantly reversed the Meth-induced upregulation of CCR5, demonstrating that the Meth-induced effect is mediated via the D2 receptor. These studies report for the first time that Meth fosters HIV-1 infection, potentially via upregulating coreceptor gene expression. Further, Meth mediates its regulatory effects via dopamine receptors and via downregulating ERK2 with a reciprocal upregulation of p38 MAPK. Elucidation of the role of Meth in HIV-1 disease susceptibility and the mechanism through which Meth mediates its effects on HIV-1 infection may help to devise novel therapeutic strategies against HIV-1 infection in high-risk Meth-using HIV-1-infected subjects.
Available from: Venkata Subba Rao Atluri
- "Moreover, in HIV infected meth abusers, a more cognitive impairment was related to a smaller hippocampal volume (Berman et al., 2008). The expression of HIV co-receptors, CXCR4 and CCR5, and HIV replication in astrocytes were both increased in presence of meth (Nair et al., 2009). BBB dysfunction and an increase in the expression of pro-inflammatory cytokinesis were observed, which can lead to meth-neurotoxicity (Czub et al., 2001; Nath et al., 2002). "
Frontiers in Microbiology 03/2015; 6:217. DOI:10.3389/fmicb.2015.00217 · 3.99 Impact Factor
Available from: Luis Martinez
- "HIV infection is highly regulated by the expression of the HIV entry co-receptors CXCR4 and CCR5. METH-treated groups demonstrated that both of these receptors exhibited up-regulated expression after METH treatment on dendritic cells, signifying increased susceptibility to HIV infection (Liang et al., 2008; Nair et al., 2009; Nair and Saiyed, 2011). In addition, METH exposure significantly reduced expression of ERK2 and up-regulated p32 MAPK genes. "
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ABSTRACT: The prevalence of methamphetamine (METH) use is estimated at ~35 million people worldwide, with over 10 million users in the United States. METH use elicits a myriad of social consequences and the behavioral impact of the drug is well understood. However, new information has recently emerged detailing the devastating effects of METH on host immunity, increasing the acquisition of diverse pathogens and exacerbating the severity of disease. These outcomes manifest as modifications in protective physical and chemical defenses, pro-inflammatory responses, and the induction of oxidative stress pathways. Through these processes, significant neurotoxicities arise, and, as such, chronic abusers with these conditions are at a higher risk for heightened consequences. METH use also influences the adaptive immune response, permitting the unrestrained development of opportunistic diseases. In this review, we discuss recent literature addressing the impact of METH on infection and immunity, and identify areas ripe for future investigation.
Frontiers in Neuroscience 01/2014; 8:445. DOI:10.3389/fnins.2014.00445 · 3.66 Impact Factor
Available from: Samikkannu Thangavel
- "Studies have reported that HIV infections are enhanced by METH, cocaine and alcohol use in vitro and in vivo[21,25,26]. Population and clinical studies have demonstrated that illicit drugs interact with HIV-positive subjects and accelerate viral replication and disease progression synergistically, by impairing immune and neuronal functions [18,27,28]. We measured acute phase proteins CRP and SAA in plasma from METH, cocaine and alcohol users alone or from HIV-positive subjects with drugs of abuse cocaine, METH and alcohol subjects using the ELISA method. "
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ABSTRACT: HIV infection and drugs of abuse such as methamphetamine (METH), cocaine, and alcohol use have been identified as risk factors for triggering inflammation. Acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) are the biomarkers of inflammation. Hence, the interactive effect of drugs of abuse with acute phase proteins in HIV-positive subjects was investigated.
Plasma samples were utilized from 75 subjects with METH use, cocaine use, alcohol use, and HIV-positive alone and HIV-positive METH, cocaine, and alcohol users, and age-matched control subjects. The plasma CRP and SAA levels were measured by ELISA and western blot respectively and the CD4 counts were also measured.
Observed results indicated that the CRP and SAA levels in HIV-positive subjects who are METH, cocaine and alcohol users were significantly higher when compared with either drugs of abuse or HIV-positive alone. The CD4 counts were also dramatically reduced in HIV-positive with drugs of abuse subjects compared with only HIV-positive subjects.
These results suggest that, in HIV-positive subjects, drugs of abuse increase the levels of CRP and SAA, which may impact on the HIV infection and disease progression.
Journal of Neuroinflammation 09/2013; 10(1):113. DOI:10.1186/1742-2094-10-113 · 5.41 Impact Factor
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