Increased Plasma Levels of the TH2 chemokine CCL18 associated with low CD4+ T cell counts in HIV-1-infected Patients with a Suppressed Viral Load

The chemokine (C-C motif) chemokine ligand 18 (CCL18) is a structural homolog of CCL3 primarily produced by monocyte-derived cells with an M2 phenotype. Elevated levels of CCL18 have been observed in several diseases associated with malignancies and chronic inflammation. The role of CCL18 in Human Immunodeficiency Virus (HIV-1) infection remains unknown. We analyzed expression levels of T helper cell-mediated (TH2) chemokines CCL18, CCL17, and CCL22 by ELISA in plasma collected from HIV-1-infected and healthy donors. In HIV-1-infected individuals, plasma viral loads were monitored by NucliSense HIV-1 QT assay and T cell counts and expression of the activation marker CD38 were determined by flow cytometry. Our data showed a significant increase in plasma levels of CCL18 in HIV-1-infected individuals compared to uninfected controls (p \u3c 0.001) and a significant correlation between CCL18 levels and viral load in untreated patients. No significant difference of CCL18 levels was detected among the HIV-1-infected patients treated with combined antiretroviral therapy (cART) and HIV-1-untreated patients.CCL18 values are negatively correlated with CD4+CD38+ cell numbers and total CD4+ T cell counts in patients with a suppressed viral load. Notably, plasma levels of the TH2 chemokines CCL17 and CCL22 are also elevated during HIV-1 infection. However, no correlation of CCL17 and CCL22 production with CD4+ T cell counts was detected. Presented data shows that the chemokines, CCL17, CCL18, and CCL22 are increased during HIV-1 infection. However, only increased levels of CCL18, a marker of M2 macrophages, correlate with low CD4+ T cell counts in patients with suppressed viral load, raising the possibility that CCL18 and/or CCL18-producing cells may interfere with their reconstitution in HIV-1-infected patients on cART

Studies of jet mass in dijet and W/Z plus jet events

This is the pre-print version of the final published paper that is available from the link below.Invariant mass spectra for jets reconstructed using the anti-kT and Cambridge-Aachen algorithms are studied for different jet “grooming” techniques in data corresponding to an integrated luminosity of 5 fb-1, recorded with the CMS detector in proton-proton collisions at the LHC at a center-of-mass energy of 7TeV. Leading-order QCD predictions for inclusive dijet and W/Z+jet production combined with parton-shower Monte Carlo models are found to agree overall with the data, and the agreement improves with the implementation of jet grooming methods used to distinguish merged jets of large transverse momentum from softer QCD gluon radiation

Macrophage Inflammatory Protein 1α Inhibits Postentry Steps of Human Immunodeficiency Virus Type 1 Infection via Suppression of Intracellular Cyclic AMP

Primary isolates of human immunodeficiency virus type 1 (HIV-1) predominantly use chemokine receptor CCR5 to enter target cells. The natural ligands of CCR5, the β-chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES, interfere with HIV-1 binding to CCR5 receptors and decrease the amount of virions entering cells. Although the inhibition of HIV-1 entry by β-chemokines is well documented, their effects on postentry steps of the viral life cycle and on host cell components that control the outcome of infection after viral entry are not well defined. Here, we show that all three β-chemokines, and MIP-1α in particular, inhibit postentry steps of the HIV-1 life cycle in primary lymphocytes, presumably via suppression of intracellular levels of cyclic AMP (cAMP). Productive HIV-1 infection of primary lymphocytes requires cellular activation. Cell activation increases intracellular cAMP, which is required for efficient synthesis of proviral DNA during early steps of viral infection. Binding of MIP-1α to cognate receptors decreases activation-induced intracellular cAMP levels through the activation of inhibitory G proteins. Furthermore, inhibition of one of the downstream targets of cAMP, cAMP-dependent PKA, significantly inhibits synthesis of HIV-1-specific DNA without affecting virus entry. These data reveal that β-chemokine-mediated inhibition of virus replication in primary lymphocytes combines inhibitory effects at the entry and postentry levels and imply the involvement of β-chemokine-induced signaling in postentry inhibition of HIV-1 infection