Power Estimation in LTE systems with the General Framework of Standard Interference Mappings

We devise novel techniques to obtain the downlink power inducing a given load in long-term evolution (LTE) systems, where we define load as the fraction of resource blocks in the time-frequency grid being requested by users from a given base station. These techniques are particularly important because previous studies have proved that the data rate requirement of users can be satisfied with lower transmit energy if we allow the load to increase. Those studies have also shown that obtaining the power assignment from a desired load profile can be posed as a fixed point problem involving standard interference mappings, but so far the mappings have not been obtained explicitly. One of our main contributions in this study is to close this gap. We derive an interference mapping having as its fixed point the power assignment inducing a desired load, assuming that such an assignment exists. Having this mapping in closed form, we simplify the proof of the aforementioned known results, and we also devise novel iterative algorithms for power computation that have many numerical advantages over previous methods.Comment: IEEE Global SIP 201

Blood CXCR3(+) CD4 T Cells Are Enriched in Inducible Replication Competent HIV in Aviremic Antiretroviral Therapy-Treated Individuals

We recently demonstrated that lymph nodes (LNs) PD-1+/T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals. In the present study, we show that blood CXCR3-expressing memory CD4 T cells are enriched in cells containing inducible replication competent virus and contributed the most to the total pool of cells containing replication competent and infectious virus in blood. Interestingly, subsequent proviral sequence analysis did not indicate virus compartmentalization between blood and LN CD4 T-cell populations, suggesting dynamic interchanges between the two compartments. We then investi-gated whether the composition of blood HIV reservoir may reflect the polarization of LN CD4 T cells at the time of reservoir seeding and showed that LN PD-1+ CD4 T cells of viremic untreated HIV-infected individuals expressed significantly higher levels of CXCR3 as compared to CCR4 and/or CCR6, suggesting that blood CXCR3-expressing CD4 T cells may originate from LN PD-1+ CD4 T cells. Taken together, these results indicate that blood CXCR3-expressing CD4 T cells represent the major blood compartment con-taining inducible replication competent virus in treated aviremic HIV-infected individuals

Latency profiles of full length HIV-1 molecular clone variants with a subtype specific promoter

<p>Abstract</p> <p>Background</p> <p>HIV-1 transcription initiation depends on cellular transcription factors that bind to promoter sequences in the Long Terminal Repeat (LTR). Each HIV-1 subtype has a specific LTR promoter configuration and even minor sequence changes in the transcription factor binding sites (TFBS) or their arrangement can impact transcriptional activity. Most latency studies have focused on HIV-1 subtype B strains, and the degree to which LTR promoter variation contributes to differences in proviral latency is therefore largely unknown. Latency differences may influence establishment and size of viral reservoirs as well as the possibility to clear the virus by therapeutic intervention.</p> <p>Results</p> <p>We investigated the proviral transcriptional latency properties of different HIV-1 subtypes as their LTRs have unique assemblies of transcription factor binding sites. We constructed recombinant viral genomes with the subtype-specific promoters inserted in the common backbone of the subtype B LAI isolate. The recombinant viruses are isogenic, except for the core promoter region that encodes all major TFBS, including NFκB and Sp1 sites. We developed and optimized an assay to investigate HIV-1 proviral latency in T cell lines. Our data show that the majority of HIV-1 infected T cells only start viral gene expression after TNFα activation.</p> <p>Conclusions</p> <p>There were no gross differences among the subtypes, both in the initial latency level and the activation response, except for subtype AE that combines an increased level of basal transcription with a reduced TNFα response. This subtype AE property is related to the presence of a GABP instead of NFκB binding site in the LTR.</p

Varied sensitivity to therapy of HIV-1 strains in CD4+ lymphocyte sub-populations upon ART initiation

<p>Abstract</p> <p>Background</p> <p>Although antiretroviral therapy (ART) has proven its success against HIV-1, the long lifespan of infected cells and viral latency prevent eradication. In this study we analyzed the sensitivity to ART of HIV-1 strains in naïve, central memory and effector memory CD4⁺lymphocyte subsets.</p> <p>Methods</p> <p>From five patients cellular HIV-1 infection levels were quantified before and after initiation of therapy (2-5 weeks). Through sequencing the C2V3 region of the HIV-1 gp120 envelope, we studied the effect of short-term therapy on virus variants derived from naïve, central memory and effector memory CD4⁺lymphocyte subsets.</p> <p>Results</p> <p>During short-term ART, HIV-1 infection levels declined in all lymphocyte subsets but not as much as RNA levels in serum. Virus diversity in the naïve and central memory lymphocyte populations remained unchanged, whilst diversity decreased in serum and the effector memory lymphocytes. ART differentially affected the virus populations co-circulating in one individual harboring a dual HIV-1 infection. Changes in V3 charge were found in all individuals after ART initiation with increases within the effector memory subset and decreases found in the naïve cell population.</p> <p>Conclusions</p> <p>During early ART virus diversity is affected mainly in the serum and effector memory cell compartments. Differential alterations in V3 charge were observed between effector memory and naïve populations. While certain cell populations can be targeted preferentially during early ART, some virus strains demonstrate varied sensitivity to therapy, as shown from studying two strains within a dual HIV-1 infected individual.</p

Measuring the Success of HIV-1 Cure Strategies

HIV-1 eradication strategies aim to achieve viral remission in the absence of antiretroviral therapy (ART). The development of an HIV-1 cure remains challenging due to the latent reservoir (LR): long-lived CD4 T cells that harbor transcriptionally silent HIV-1 provirus. The LR is stable despite years of suppressive ART and is the source of rebound viremia following therapy interruption. Cure strategies such as "shock and kill" aim to eliminate or reduce the LR by reversing latency, exposing the infected cells to clearance via the immune response or the viral cytopathic effect. Alternative strategies include therapeutic vaccination, which aims to prime the immune response to facilitate control of the virus in the absence of ART. Despite promising advances, these strategies have been unable to significantly reduce the LR or increase the time to viral rebound but have provided invaluable insight in the field of HIV-1 eradication. The development and assessment of an HIV-1 cure requires robust assays that can measure the LR with sufficient sensitivity to detect changes that may occur following treatment. The viral outgrowth assay (VOA) is considered the gold standard method for LR quantification due to its ability to distinguish intact and defective provirus. However, the VOA is time consuming and resource intensive, therefore several alternative assays have been developed to bridge the gap between practicality and accuracy. Whilst a cure for HIV-1 infection remains elusive, recent advances in our understanding of the LR and methods for its eradication have offered renewed hope regarding achieving ART free viral remission