Intragenic transcriptional cis-activation of the human immunodeficiency virus 1 does not result in allele-specific inhibition of the endogenous gene

<p>Abstract</p> <p>Background</p> <p>The human immunodeficiency virus type 1 (HIV-1) favors integration in active genes of host chromatin. It is believed that transcriptional interference of the viral promoter over the endogenous gene or vice versa might occur with implications in HIV-1 post-integrative transcriptional latency.</p> <p>Results</p> <p>In this work a cell line has been transduced with a HIV-based vector and selected for Tat-inducible expression. These cells were found to carry a single silent integration in sense orientation within the second intron of the <it>HMBOX1 </it>gene. The HIV-1 Tat transactivator induced the viral LTR and repressed <it>HMBOX1 </it>expression independently of vector integration. Instead, single-cell quantitative <it>in situ </it>hybridization revealed that allele-specific transcription of <it>HMBOX1 </it>carrying the integrated provirus was not affected by the transactivation of the viral LTR in <it>cis</it>.</p> <p>Conclusion</p> <p>A major observation of the work is that the HIV-1 genome has inserted in genes that are also repressed by Tat and this could be an advantage for the virus during transcriptional reactivation. In addition, it has also been observed that transcription of the provirus and of the endogenous gene in which it is integrated may coexist at the same time in the same genomic location.</p

Neonatal Outcomes of Water Delivery versus Land Delivery: A Retrospective Propensity Score Weighted Study

Objective:  Recent evidence has shown that water delivery is safe for the mother, but high-quality evidence is not available for the newborn. Therefore, obstetric guidelines do not support it. This retrospective study aimed to contribute to the available evidence on maternal and neonatal outcomes associated with water delivery. Study design:  Retrospective cohort study from prospectively collected birth registry data from 2015 to 2019. A total of 144 consecutive water deliveries and 265 land deliveries eligible for waterbirth were identified. The inverse probability of treatment weighting (IPTW) method was applied to address for confounders. Results:  We identified 144 women who delivered in water (water group) and 265 women who delivered on land (land group). One (0.7%) neonatal death was observed in the water delivery group. After IPTW adjustment, water delivery was significantly associated with a higher risk of maternal fever in puerperium (odds ratio [OR]: 4.98; 95% confidence interval [CI]: 1.86-17.02; p = 0.004), of neonatal cord avulsion (OR: 20.73; 95% CI: 2.63-2,674; p = 0.001), and of positive neonatal C-reactive protein (CRP &gt; 5 mg/L; OR: 2.59; 95% CI: 1.05-7.24; p = 0.039); delivering in water was associated with lower maternal blood loss (mean difference: 110.40 mL; 95% CI: 191.01-29.78; p = 0.007), a lower risk of major (≥1,000 mL) postpartum hemorrhage (OR: 0.96; 95% CI: 0.92-0.99; p = 0.016), lower risk of manual placenta delivery (OR: 0.18; 95% CI: 0.03-0.67; p = 0.008) and curettage (OR: 0.24; 95% CI: 0.08-0.60; p = 0.002), lower use of episiotomy (OR: 0.02; 95% CI: 0-0.12; p &lt; 0.001), and lower risk of neonatal ward admission (OR: 0.35; 95% CI: 0.25-0.48; p &lt; 0.001). Conclusion:  The present study showed that differences are present between water and land delivery, and among them is the risk of cord avulsion, a severe and potentially fatal event. In women choosing to deliver in water, a trained staffmust be present and immediate recognition of cord avulsion is key for a prompt management to avoid possible serious complications. Key points: · High-quality evidence is not available for neonatal safety of waterbirth; therefore, retrospective studies still represent the main body of evidence.. · Differences are present between water and land delivery, and among them, the increased risk of cord avulsion is a potentially fatal event.. · A trained staff must assist women who chose to deliver in water and cord avulsion must be promptly recognized and managed to avoid severe neonatal complications.

Transcriptional competence of the integrated HIV-1 provirus at the nuclear periphery

Spatial distribution of genes within the nucleus contributes to transcriptional control, allowing optimal gene expression as well as constitutive or regulated gene repression. Human immunodeficiency virus type 1 (HIV-1) integrates into host chromatin to transcribe and replicate its genome. Lymphocytes harbouring a quiescent but inducible provirus are a challenge to viral eradication in infected patients undergoing antiviral therapy. Therefore, our understanding of the contribution of sub-nuclear positioning to viral transcription may also have far-reaching implications in the pathology of the infection. To gain an insight into the conformation of chromatin at the site of HIV-1 integration, we investigated lymphocytes carrying a single latent provirus. In the silenced state, the provirus was consistently found at the nuclear periphery, associated in trans with a pericentromeric region of chromosome 12 in a significant number of quiescent cells. After induction of the transcription, this association was lost, although the location of the transcribing provirus remained peripheral. These results, extended to several other cell clones, unveil a novel mechanism of transcriptional silencing involved in HIV-1 post-transcriptional latency and reinforce the notion that gene transcription may also occur at the nuclear periphery