Peptides Derived from HIV-1 Integrase that Bind Rev Stimulate Viral Genome Integration

The human immunodeficiency virus type 1 (HIV-1) integrase protein (IN), catalyzes the integration of viral DNA into the host cell genome. IN catalyzes the first step of the integration process, namely the 3′-end processing in which IN removes a pGT dinucleotide from the 3′ end of each viral long terminal repeat (LTR). Following nuclear import of the viral preintegration complex, the host chromosomal DNA becomes accessible to the viral cDNA and the second step of the integration process, namely the strand-transfer step takes place. This ordered sequence of events, centered on integration, is mandatory for HIV replication. assay system, we show that INr-1 and INr-2 are able to abrogate the inhibitory effects exerted by Rev and Rev-derived peptides on integrase activity. Both INr-1 and INr-2 were found to be cell-permeable and nontoxic, allowing a study of their effect in HIV-1-infected cultured cells. Interestingly, both INr peptides stimulated virus infectivity as estimated by production of the viral P24 protein, as well as by determination of the appearance of newly formed virus particles. Furthermore, kinetics studies revealed that the cell-permeable INr peptides enhance the integration process, as was indeed confirmed by direct determination of viral DNA integration by real-time PCR.The results of the present study raise the possibility that in HIV-infected cells, the Rev protein may be involved in the integration of proviral DNA by controlling/regulating the activity of the integrase. Release from such inhibition leads to stimulation of IN activity and multiple viral DNA integration events

Supplementary Material for: Breastfeeding success and newborn health before and during the COVID-19 pandemic: a single centre comparative study

Introduction: Due to the SARS-CoV-2 pandemic, adjustments in patient and visitor traffic were made in hospitals to limit viral exposure. The primary objective of our study was to compare the breastfeeding success of healthy newborns in a maternity ward during the 2020 lockdown period compared with the same period in the previous year. Material and methods: single-center comparative study based on prospectively collected data. All neonates born alive, from a single pregnancy, and with a gestational age greater than 36 weeks were considered for this study. Results: 309 infants born in 2020 and 330 born in 2019 were included. Among women who desired to exclusively breastfeed, the rate of exclusive breastfeeding at discharge from the maternity ward was higher in 2020 than in 2019 (85% vs. 79%; p=0.078). After logistic regression analysis adjusted for potential confounders (i.e., maternal BMI, parity, mode of delivery, gestational age, and size at birth), study period remained significantly and independently associated with exclusive breastfeeding at discharge(OR [95%IC] = 1.645 [1.005; 2.694]; p=0.046). Newborns born in 2020 were less likely to have weight loss ≥10% than those born in 2019 (OR [95%IC] = 2.596 [1.148; 5.872]; p=0.017) but had similar need for phototherapy (p=0.41). Conclusion: The success of exclusive breastfeeding during the 2020 lockdown period was increased compared with the same period in 2019

It's time to change the recommendations on COVID-19 and human milk donations

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Bacillus cereus infection in neonates and the absence of evidence for the role of banked human milk: Case reports and literature review

International audienceBACKGROUND: Banked human milk (BHM) has inherent infectious risks, even when pasteurized. Because of the ubiquity of Bacillus cereus in the environment and its ability to resist the Holder pasteurization process, there is a concern that BHM might lead to severe B. cereus infections. OBJECTIVE: We reviewed observed and published cases to determine the potential causal role of BHM as the source of these infections. METHODS: Two infants in the province of Quebec (Canada) developed a B. cereus neonatal infection, and both had received BHM. We conducted bacteriological studies to compare clinical isolates and those found in these cases. RESULTS: After extended culture of BHM retention lots, B. cereus was found to have been involved in batches related to the first case. However, molecular typing showed that the strain was different from the clinical isolate, therefore excluding BHM as the source of contamination. In the second case, a Brevibacillus spp was isolated, a species distinct from the clinical isolate. CONCLUSION: Based on these cases and others reported in the literature, a causal link between B. cereus contaminated BHM and preterm neonatal infection has never been documented. Therefore, the risk that BHM can cause this infection remains theoretical. Given the widespread presence of B. cereus in the hospital environment and its capacity to resist standard cleaning procedures, it seems likely that airborne or direct or indirect contact are the main sources of most, if not all, cases of severe B. cereus neonatal infections, even in babies exposed to BHM

Combination of promoter hypomethylation and PDX1 overexpression leads to TBX15 decrease in vascular IUGR placentas

Preeclampsia (PE) and vascular intra-uterine growth restriction (vIUGR) are two pathological obstetrical conditions originating from placental dysfunction. Recently, methylation changes at the placental level have been shown to be indicative of these diseases. The alteration of such epigenetic marks is therefore a novel pathway that might be critical for these pathologies. Here, we identified a region located in the distal promoter of the T-box-containing transcription factor TBX15 that is differentially methylated in pathological placentas. The level of methylation correlated significantly with the weight and stature of the newborn. The promoter was found to be hypomethylated in vIUGR coinciding with the down-regulation of its expression. PDX1, a transcription factor important for the regulation of insulin metabolism regulation was able to repress the TBX15 promoter in a methylation-dependent manner, which might, at least partially, explain the specific mRNA decrease of TBX15 observed in vIUGR placentas. Overall, the data presented herein suggest that TBX15 might be involved in the pathophysiology of placental diseases

A hierarchical analysis of transcriptome alterations in intrauterine growth restriction (IUGR) reveals common pathophysiological pathways in mammals

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