Journey to the heart of macrophages: the delicate relationship between HIV-1 and a multifaceted cell type

International audienceCells of the monocyte-macrophage lineage play multiple roles during the infection of primate lentiviruses serving as reservoirs for viral production or as vectors for viral spread to other cells and tissues. The human immunodeficiency type I virus is not only capable of establishing such complex and dynamic relations with this cell type, but is also able to modulate their physiology and behavior, thus shaping ensuing cellular immune responses. In this issue of Retrovirology, a series of reviews explores the multiple manners in which the virus and cells belonging to the monocyte-macrophage lineage interact and affect each other

The Inside Out of Lentiviral Vectors

Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we shall describe the main basic aspects of the virology of lentiviruses that were exploited to obtain efficient gene transfer vectors. In addition, we shall discuss some of the hurdles that oppose the efficient genetic modification mediated by lentiviral vectors and the strategies that are being developed to circumvent them

Prediction of turbulence control for arbitrary periodic spanwise wall movement

In order to generalize the well-known spanwise-oscillating-wall technique for drag reduction, non-sinusoidal oscillations of a solid wall are considered as a means to alter the skin-friction drag in a turbulent channel flow. A series of Direct Numerical Simulations is conducted to evaluate the control performance of nine different temporal waveforms, in addition to the usual sinusoid, systematically changing the wave amplitude and the period for each waveform. The turbulent average spanwise motion is found to coincide with the laminar Stokes solution that is constructed, for the generic waveform, through harmonic superposition. This allows us to define and compute, for each waveform, a new penetration depth of the Stokes layer which correlates with the amount of turbulent drag reduction, and eventually to predict both turbulent drag reduction and net energy saving rate for arbitrary waveforms. Among the waveforms considered, the maximum net energy saving rate is obtained by the sinusoidal wave at its optimal amplitude and period. However, the sinusoid is not the best waveform at every point in the parameter space. Our predictive tool offers simple guidelines to design waveforms that outperform the sinusoid for given (suboptimal) amplitude and period of oscillation. This is potentially interesting in view of applications, where physical limitations often preclude the actuator to reach its optimal operating conditions

Structure function tensor equations in inhomogeneous turbulence

Exact budget equations for the second-order structure function tensor ⟨u$_{i}$u$_{j}$⟩, where u is the difference of the i th fluctuating velocity component between two points, are used to study the two-point statistics of velocity fluctuations in inhomogeneous turbulence. The anisotropic generalised Kolmogorov equations (AGKE) describe the production, transport, redistribution and dissipation of every Reynolds stress component occurring simultaneously among different scales and in space, i.e. along directions of statistical inhomogeneity. The AGKE are effective to study the inter-component and multi-scale processes of turbulence. In contrast to more classic approaches, such as those based on the spectral decomposition of the velocity field, the AGKE provide a natural definition of scales in the inhomogeneous directions, and describe fluxes across such scales too. Compared to the generalised Kolmogorov equation, which is recovered as their half-trace, the AGKE can describe inter-component energy transfers occurring via the pressure–strain term and contain also budget equations for the off-diagonal components of ⟨u$_{i}$u$_{j}$⟩. The non-trivial physical interpretation of the AGKE terms is demonstrated with three examples. First, the near-wall cycle of a turbulent channel flow at a friction Reynolds number of Re$_{}$ = 200 is considered. The off-diagonal component ⟨-uυ⟩, which cannot be interpreted in terms of scale energy, is discussed in detail. Wall-normal scales in the outer turbulence cycle are then discussed by applying the AGKE to channel flows at Re$_{}$ = 500 and 1000. In a third example, the AGKE are computed for a separating and reattaching flow. The process of spanwise-vortex formation in the reverse boundary layer within the separation bubble is discussed for the first time

Experimental and Numerical Analysis of the Hydrodynamics around a Vertical Cylinder in Waves

The present study provides an extensive analysis on the hydrodynamics induced by a vertical slender pile under wave action. The authors carried out the study both experimentally and numerically, thus enabling a deep understanding of the flow physics. The experiments took place at a wave flume of the Universita Politecnica delle Marche. Two different experimental campaigns were performed: In the former one, a mobile bed model was realized with the aims to study both the scour process and the hydrodynamics around the cylinder; in the latter one, the seabed was rigid in order to make undisturbed optical measurements, providing a deeper analysis of the hydrodynamics. The numerical investigation was made by performing a direct numerical simulation. A second order numerical discretization, both in time and in space, was used to solve the Navier-Stokes equations while a volume of fluid (VOF) approach was adopted for tracking the free surface. The comparison between experimental and numerical results is provided in terms of velocity, pressure distributions around the cylinder, and total force on it. The analysis of the pressure gradient was used to evaluate the generation and evolution of vortices around the cylinder. Finally, the relation between scour and bed shear stresses due to the structure of the vortex pattern around the pile was assessed. It is worth noting that the physical understanding of this last analysis was enabled by the combined use of experimental data on scour and numerical data on the flow pattern

SIV(SM)/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent restriction pathway present in human dendritic cells

BACKGROUND: Vpx is a non-structural protein coded by members of the SIV(SM)/HIV-2 lineage that is believed to have originated by duplication of the common vpr gene present in primate lentiviruses. Vpx is incorporated into virion particles and is thus present during the early steps of viral infection, where it is thought to drive nuclear import of viral nucleoprotein complexes. We have previously shown that Vpx is required for SIV(MAC)-derived lentiviral vectors (LVs) infection of human monocyte-derived dendritic cells (DCs). However, since the requirement for Vpx is specific for DCs and not for other non-dividing cell types, this suggests that Vpx may play a role other than nuclear import. RESULTS: Here, we show that the function of Vpx in the infection of DCs is conserved exclusively within the SIV(SM)/HIV-2 lineage. At a molecular level, Vpx acts by promoting the accumulation of full length viral DNA. Furthermore, when supplied in target cells prior to infection, Vpx exerts a similar effect following infection of DCs with retroviruses as divergent as primate and feline lentiviruses and gammaretroviruses. Lastly, the effect of Vpx overlaps with that of the proteasome inhibitor MG132 in DCs. CONCLUSION: Overall, our results support the notion that Vpx modifies the intracellular milieu of target DCs to facilitate lentiviral infection. The data suggest that this is achieved by promoting viral escape from a proteasome-dependent pathway especially detrimental to viral infection in DCs