Analysis of infectious virus clones from two HIV-1 superinfection cases suggests that the primary strains have lower fitness

<p>Abstract</p> <p>Background</p> <p>Two HIV-1 positive patients, L and P, participating in the Amsterdam Cohort studies acquired an HIV-1 superinfection within half a year from their primary HIV-1 infection (Jurriaans <it>et al</it>., <it>JAIDS </it>2008, <b>47:</b>69-73). The aim of this study was to compare the replicative fitness of the primary and superinfecting HIV-1 strains of both patients. The use of isolate-specific primer sets indicated that the primary and secondary strains co-exist in plasma at all time points after the moment of superinfection.</p> <p>Results</p> <p>Biological HIV-1 clones were derived from peripheral blood CD4 + T cells at different time point, and identified as the primary or secondary virus through sequence analysis. Replication competition assays were performed with selected virus pairs in PHA/IL-2 activated peripheral blood mononuclear cells (PBMC's) and analyzed with the Heteroduplex Tracking Assay (HTA) and isolate-specific PCR amplification. In both cases, we found a replicative advantage of the secondary HIV-1 strain over the primary virus. Full-length HIV-1 genomes were sequenced to find possible explanations for the difference in replication capacity. Mutations that could negatively affect viral replication were identified in the primary infecting strains. In patient L, the primary strain has two insertions in the LTR promoter, combined with a mutation in the <it>tat </it>gene that has been associated with decreased replication capacity. The primary HIV-1 strain isolated from patient P has two mutations in the LTR that have been associated with a reduced replication rate. In a luciferase assay, only the LTR from the primary virus of patient P had lower transcriptional activity compared with the superinfecting virus.</p> <p>Conclusions</p> <p>These preliminary findings suggest the interesting scenario that superinfection occurs preferentially in patients infected with a relatively attenuated HIV-1 isolate.</p

The predominance of Human Immunodeficiency Virus type 1 (HIV-1) circulating recombinant form 02 (CRF02_AG) in West Central Africa may be related to its replicative fitness

BACKGROUND: CRF02_AG is the predominant HIV strain circulating in West and West Central Africa. The aim of this study was to test whether this predominance is associated with a higher in vitro replicative fitness relative to parental subtype A and G viruses. Primary HIV-1 isolates (10 CRF02_AG, 5 subtype A and 5 subtype G) were obtained from a well-described Cameroonian cohort. Growth competition experiments were carried out at equal multiplicity of infection in activated T cells and monocyte-derived dendritic cells (MO-DC) in parallel. RESULTS: Dual infection/competition experiments in activated T cells clearly indicated that CRF02_AG isolates had a significant replication advantage over the subtype A and subtype G viruses. The higher fitness of CRF02_AG was evident for isolates from patients with CD4+ T cell counts >200 cells/μL (non-AIDS) or CD4+ T cell counts <200 cells/μL (AIDS), and was independent of the co-receptor tropism. In MO-DC cultures, CRF02_AG isolates showed a slightly but not significantly higher replication advantage compared to subtype A or G isolates. CONCLUSION: We observed a higher ex vivo replicative fitness of CRF02_AG isolates compared to subtype A and G viruses from the same geographic region and showed that this was independent of the co-receptor tropism and irrespective of high or low CD4+ T cell count. This advantage in replicative fitness may contribute to the dominant spread of CRF02_AG over A and G subtypes in West and West Central Africa

Effect of a full pilates group exercise program on transversus abdominis thickness, daily function and pain in women with chronic low back pain

The Pilates method is often used in the treatment of nonspecific low back pain (NSCLBP). The effect of Pilates group exercising (mat and apparatus combined) on women with NSCLBP is unknown. Studies on the Pilates method often use ultrasound (US) to measure transversus abdominis (TrA) thickness in one anatomical location. We recruited 40 women, 22 with NSCLBP and 18 healthy women (active control group), to join five weeks of biweekly Pilates group exercising (apparatus and mat). Measurements included TrA thickness (left and right) at rest, during active draw-in maneuver (ADIM), and its TrA% change in three anatomical areas; Roland-Morris disability questionnaire (RMDQ); and pain level (VAS). Before the study, no asymmetry in TrA thickness was noted as well as no between-group differences in TrA-thickness in three anatomic areas (in rest and ADIM). Following the intervention, TrA thickness increased during rest in the healthy group in two areas. No differences were noted between the two groups in ADIM in the anatomical locations. No between-group differences were found before the intervention in the TrA% change. Following the intervention, an increase in the TrA-% change was noticed in the NSCLBP group. A decrease in the healthy group was observed in area C. No effects were noted on the RMDQ and VAS. Five weeks of Pilates group exercising increased TrA thickness in healthy women and its percentage changed in women with NSCLBP. Measuring TrA thickness with US should be performed in three different anatomical locations on both sides. This measuring procedure has good inter- and intra-rater reliability and the potential to reveal physiological effects

The Lumbar Lordosis in Males and Females, Revisited.

Whether differences exist in male and female lumbar lordosis has been debated by researchers who are divided as to the nature of variations in the spinal curve, their origin, reasoning, and implications from a morphological, functional and evolutionary perspective. Evaluation of the spinal curvature is constructive in understanding the evolution of the spine, as well as its pathology, planning of surgical procedures, monitoring its progression and treatment of spinal deformities. The aim of the current study was to revisit the nature of lumbar curve in males and females.Our new automated method uses CT imaging of the spine to measure lumbar curvature in males and females. The curves extracted from 158 individuals were based on the spinal canal, thus avoiding traditional pitfalls of using bone features for curve estimation. The model analysis was carried out on the entire curve, whereby both local and global descriptors were examined in a single framework. Six parameters were calculated: segment length, curve length, curvedness, lordosis peak location, lordosis cranial peak height, and lordosis caudal peak height.Compared to males, the female spine manifested a statistically significant greater curvature, a caudally located lordotic peak, and greater cranial peak height. As caudal peak height is similar for males and females, the illusion of deeper lordosis among females is due partially to the fact that the upper part of the female lumbar curve is positioned more dorsally (more backwardly inclined).Males and females manifest different lumbar curve shape, yet similar amount of inward curving (lordosis). The morphological characteristics of the female spine were probably developed to reduce stress on the vertebral elements during pregnancy and nursing

In Vitro Evaluation of Viability, Integrity, and Inflammation in Genital Epithelia upon Exposure to Pharmaceutical Excipients and Candidate Microbicides▿

The use of microbicides is a promising approach for the prevention of HIV-1 transmission. Unfortunately, various candidates failed in clinical trials. In some cases, the candidate microbicide even resulted in enhanced virus transmission. Therefore, there is an urgent need to develop more predictive preclinical strategies to anticipate the in vivo efficiency/toxicity rate, including in vitro assays that evaluate effects on epithelial integrity and inflammation. The present study aims to identify potential safety issues concerning the use of microbicides and excipients commonly used in vaginal microbicide preparations. The toxicities of various active pharmaceutical ingredients (APIs; TMC-120, UC-781, tenofovir [PMPA], PRO-2000, and glycerol monolaurate [GML]) and excipients (preservatives, cosolvents, surfactants, and cyclodextrins) were evaluated using an in vitro dual-chamber model and uterine cervical explants. Epithelial viability and permeation of fluorescent virus-sized beads, as well as induction of interleukin-8 (IL-8; as a sensitive marker of an inflammatory response), were assessed. Surprisingly, cell viability and epithelial layer integrity were compromised by most excipients at concentrations near the typical concentration used in vaginal gels, and a significant increase in the production of IL-8 was observed at subtoxic concentrations. Within the APIs, TMC-120, UC-781, and PMPA showed higher selectivity indices than PRO-2000 and GML. In conclusion, identification of safety issues concerning the use of pharmaceutical excipients could help to formulate less toxic vaginal microbicide preparations

Males population curve 2-D view.

<p>Male population curve 2-D views: sagittal (top) and coronal (bottom) planes. The coordinates are scaled by the vertical distance between the superior end plate of the sacrum and the inferior end plate of T12.</p