Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway

Design, fabrication, and characterization of a tissue-equivalent phantom for optical elastography

We suitably adapt the design of a tissue-equivalent phantom used for photoacoustic imaging to construct phantoms for optical elastography.The elastography phantom we consider should have optical properties such as scattering coefficient, scattering anisotropy factor, and refractive index; mechanical properties such as storage and loss modulus; and acoustic properties such as ultrasound velocity,attenuation coefficient, and acoustic impedance to match healthy and diseased tissues. The phantom is made of poly (vinyl alcohol) (PVA) andits mechanical, optical, and acoustic properties are tailored by physical cross-linking effected through subjecting a suitable mix of PVA stock and water to a number of freeze-thaw cycles and by varying the degree of hydrolysis in the PVA stock. The optical, mechanical, and acoustic properties of the samples prepared are measured by employing different techniques. The measured variations in the values of optical scattering coefficient, scattering anisotropy factor, and refractive index and storage modulus are found to be comparable to those in normal and diseased breast tissues. The acoustic properties such as sound speed, acoustic attenuation coefficient, and density are found to be close to the average values reported in the literature for normal breast tissue

Mechanical property assessment of tissue-mimicking phantoms using remote palpation and optical read-out for amplitude of vibration and refractive index modulation

A coherent light beam is used to interrogate the focal region within a tissue-mimicking phantom insonified by an ultrasound transducer. The ultrasound-tagged photons exiting from the object carry with them information on local optical path length fluctuations caused by refractive index variations and medium vibration. Through estimation of the force distribution in the focal region of the ultrasound transducer, and solving the forward elastography problem for amplitude of vibration of tissue particles, we observe that the amplitude is directed along the axis of the transducer. It is shown that the focal region interrogated by photons launched along the transducer axis carries phase fluctuations owing to both refractive index variations and particle vibration, whereas the photons launched perpendicular to the transducer axis carry phase fluctuations arising mainly from the refractive index variations, with only smaller contribution from vibration of particles. Monte-Carlo simulations and experiments done on tissue-mimicking phantoms prove that as the storage modulus of the phantom is increased, the detected modulation depth in autocorrelation is reduced, significantly for axial photons and only marginally for the transverse-directed photons. It is observed that the depth of modulation is reduced to a significantly lower and constant value as the storage modulus of the medium is increased. This constant value is found to be the same for both axial and transverse optical interrogation. This proves that the residual modulation depth is owing to refractive index fluctuations alone, which can be subtracted from the overall measured modulation depth, paving the way for a possible quantitative reconstruction of storage modulus. Moreover, since the transverse-directed photons are not significantly affected by storage modulus variations, for a quantitatively accurate read-out of absorption coefficient variation, the interrogating light should be perpendicular to the focusing ultrasound transducer axi