HIV-1 Nef Breaches Placental Barrier in Rat Model

Singh, Poonam; Agnihotri, Saurabh Kumar; Tewari, Mahesh Chandra; Kumar, Sadan; Sachdev, M. S.; Tripathi, Raj Kamal

doi:10.1371/journal.pone.0051518

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…Components of HIV such as Nef have complex effects on the immune system, including CD4 depletion, activation, and apoptosis ( 32 , 33 ). Furthermore, in a rodent model, Nef breaches placental barrier function and may enable HIV, other viral proteins and microbial products (see below) to cross the placenta ( 34 ), potentially exacerbating effects on the fetal immune system.…”

Section: Morbidity and Mortality Of Heu Infantsmentioning

confidence: 99%

“…In an animal model ( 62 ), subclinical infection with murine gammaherpesvirus 68 sensitizes pregnant mice to a greater cytokine response to LPS, suggesting that viral infections have potential to amplify the impact of LPS exposure during pregnancy. Maternal microbial translocation in HIV-affected pregnancies may plausibly contribute to immune activation in HEU infants: LPS can cross the placental barrier in mice ( 63 ), meaning that translocated maternal LPS could potentially activate fetal immune cells, particularly in the context of Nef-mediated placental barrier dysfunction ( 34 ). Whether LPS or other microbial products cross the placental barrier in HEU infants and contribute to immune activation has yet to be confirmed.…”

Section: Morbidity and Mortality Of Heu Infantsmentioning

confidence: 99%

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HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era

et al. 2016

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The ZVITAMBO trial recruited 14,110 mother–infant pairs to a randomized controlled trial of vitamin A between 1997 and 2000, before the availability of antiretroviral therapy for HIV prophylaxis or treatment in Zimbabwe. The HIV status of mothers and infants was well characterized through 1–2 years of follow-up, leading to the largest cohort to date of HIV-exposed uninfected (HEU) infants (n = 3135), with a suitable comparison group of HIV-unexposed infants (n = 9510). Here, we draw on 10 years of published findings from the ZVITAMBO trial. HEU infants had increased morbidity compared to HIV-unexposed infants, with 50% more hospitalizations in the neonatal period and 30% more sick clinic visits during infancy, particularly for skin infections, lower respiratory tract infections, and oral thrush. HEU children had 3.9-fold and 2.0-fold higher mortality than HIV-unexposed children during the first and second years of life, respectively, most commonly due to acute respiratory infections, diarrhea/dysentery, malnutrition, sepsis, and meningitis. Infant morbidity and mortality were strongly related to maternal HIV disease severity, and increased morbidity remained until maternal CD4 counts were >800 cells/μL. HEU infants were more likely to be premature and small-for-gestational age than HIV-unexposed infants, and had more postnatal growth failure. Here, we propose a conceptual framework to explain the increased risk of infectious morbidity, mortality, and growth failure among HEU infants, hypothesizing that immune activation and inflammation are key drivers of both infection susceptibility and growth failure. Future studies should further dissect the causes of infection susceptibility and growth failure and determine the impact of ART and cotrimoxazole on outcomes of this vulnerable group of infants in the current era.

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Section: Morbidity and Mortality Of Heu Infantsmentioning

confidence: 99%

Section: Morbidity and Mortality Of Heu Infantsmentioning

confidence: 99%

HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era

et al. 2016

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“…The paper by Simões et al reports a significant increase in IL-1 β , IL-6, and TNF αβ levels in the offspring brain in response to maternal cytokines [ 166 ]. The inflammatory response leads to an increase in ROS generation by endothelial cells, and, consequently, to disruption of BBB permeability [ 167 ]. In addition to the disruption of BBB and placental barrier permeability, cytokines in the brain regulate the expression of major histocompatibility complex I (MHC I), coordinating synaptic pruning [ 168 , 169 ].…”

Section: Molecular Mechanisms Of Oxidative Stress In the Pathogenementioning

confidence: 99%

Oxidative Stress‐Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives

Ermakov

Dmitrieva

Parshukova

et al. 2021

Oxidative Medicine and Cellular Longevity

138

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Schizophrenia is recognized to be a highly heterogeneous disease at various levels, from genetics to clinical manifestations and treatment sensitivity. This heterogeneity is also reflected in the variety of oxidative stress-related mechanisms contributing to the phenotypic realization and manifestation of schizophrenia. At the molecular level, these mechanisms are supposed to include genetic causes that increase the susceptibility of individuals to oxidative stress and lead to gene expression dysregulation caused by abnormal regulation of redox-sensitive transcriptional factors, noncoding RNAs, and epigenetic mechanisms favored by environmental insults. These changes form the basis of the prooxidant state and lead to altered redox signaling related to glutathione deficiency and impaired expression and function of redox-sensitive transcriptional factors (Nrf2, NF-κB, FoxO, etc.). At the cellular level, these changes lead to mitochondrial dysfunction and metabolic abnormalities that contribute to aberrant neuronal development, abnormal myelination, neurotransmitter anomalies, and dysfunction of parvalbumin-positive interneurons. Immune dysfunction also contributes to redox imbalance. At the whole-organism level, all these mechanisms ultimately contribute to the manifestation and development of schizophrenia. In this review, we consider oxidative stress-related mechanisms and new treatment perspectives associated with the correction of redox imbalance in schizophrenia. We suggest that not only antioxidants but also redox-regulated transcription factor-targeting drugs (including Nrf2 and FoxO activators or NF-κB inhibitors) have great promise in schizophrenia. But it is necessary to develop the stratification criteria of schizophrenia patients based on oxidative stress-related markers for the administration of redox-correcting treatment.

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“…For successful infection, viruses have developed several strategies to promote an ideal microenvironment in order to maintain viral persistence and optimize their infection cycle (Amara and Mercer 2015;Harak and Lohmann 2015;Vijaykrishna, Mukerji and Smith 2015). Several studies have reported the mechanisms via which viruses infecting the maternal-fetal interface can promote a series of pathogenic processes; these processes greatly depend on the expression of specific viral genes whose products are key players in the replication and efficient dissemination of the viruses (Singh et al 2012;Aldo et al 2016). For the purpose of this minireview, these pathogenic mechanisms will be classified with respect to the following: (i) modulation of cell apoptosis; (ii) impact of the immune response; and (iii) mechanisms underlying invasion and vascular damage during viral infection.…”

Section: Pathogenic Mechanisms In Trophoblasts During Viral Infectionsmentioning

confidence: 99%

Cellular and molecular mechanisms of viral infection in the human placenta

León-Juárez

Martínez-Castillo

González-García

et al. 2017

Pathogens and Disease

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The placenta is a highly specialized organ that is formed during human gestation for conferring protection and generating an optimal microenvironment to maintain the equilibrium between immunological and biochemical factors for fetal development. Diverse pathogens, including viruses, can infect several cellular components of the placenta, such as trophoblasts, syncytiotrophoblasts and other hematopoietic cells. Viral infections during pregnancy have been associated with fetal malformation and pregnancy complications such as preterm labor. In this minireview, we describe the most recent findings regarding virus-host interactions at the placental interface and investigate the mechanisms through which viruses may access trophoblasts and the pathogenic processes involved in viral dissemination at the maternal-fetal interface.

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HIV-1 Nef Breaches Placental Barrier in Rat Model

Cited by 8 publications

References 36 publications

HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era

HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era

Oxidative Stress‐Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives

Cellular and molecular mechanisms of viral infection in the human placenta

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