共查询到20条相似文献,搜索用时 15 毫秒
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Junran Cao Shaolin Wang Ju Wang Wenyan Cui Tanseli Nesil Michael Vigorito Sulie L. Chang Ming D. Li 《PloS one》2013,8(7)
Persons infected with HIV-1 often develop neurologic disorders despite receiving highly active anti-retroviral therapy. Although the underlying mechanism is largely undetermined, our previous RNA-seq-based study showed that the expression of many genes was altered in the central nervous system (CNS) of HIV-1 transgenic (HIV-1Tg) rats. Because nicotine, a natural agonist of nicotinic acetylcholine receptors, exhibits a neuroprotective effect, we presently tested the hypothesis that nicotine restores the expression of altered genes in the CNS of HIV-1Tg rats. Adult male HIV-1Tg and F344 control strain rats were injected with either nicotine (0.25 mg/kg) or saline subcutaneously twice a day for 17 days. Gene expression in the prefrontal cortex (PFC), dorsal hippocampus (HIP), and dorsal striatum (STR) was evaluated using the RNA deep sequencing technique. We found that about 20% of the altered genes in the HIV-1Tg rat were affected by nicotine in each brain region, with the expression of most restored. Analysis of the restored genes showed distinct pathways corrected by nicotine in different brain regions of HIV-1Tg rats. Specifically, the two most significantly restored pathways were Wnt/β-catenin signaling and ephrin B signaling in the PFC, cAMP-responsive element-binding protein (CREB) signaling and glutathione metabolism pathway in the HIP, and tricarboxylic acid (TCA) cycle and calcium signaling in the STR. Together, our findings indicate that cholinergic modulators such as nicotine have beneficial effects on HIV-1-induced neurologic deficits. 相似文献
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Lund AK Lucero J Herbert L Liu Y Naik JS 《American journal of physiology. Lung cellular and molecular physiology》2011,301(3):L315-L326
Human immunodeficiency virus (HIV)-associated pulmonary arterial hypertension (PAH) is a serious noninfectious disease involving an aberrant increase in pressure in the blood vessels of the lung, which leads to right ventricular (RV) heart failure and can eventually result in death. A lack of viable animal models of HIV-PAH has limited the identification of signaling pathways involved in HIV-mediated onset and progression of PAH. To determine whether the HIV-1 transgenic (HIV Tg) rat displays pathophysiological end points associated with PAH, we evaluated peak RV systolic pressure (RVSP), RV hypertrophy, pulmonary vessel remodeling, and alterations in gene expression by real-time PCR and microarray. RVSP was measured by RV catheterization via the right jugular vein in 3- and 9-mo-old HIV Tg and age-matched Fischer 344 (control) male rats while under 2% isoflurane anesthesia. RVSP was elevated in the HIV Tg rats (34.2 ± 2.5 mmHg) compared with the F344 controls (21.2 ± 2.5 mmHg), with more significant elevations in the 9-mo-old HIV Tg rats (42.5 ± 3.7 mmHg). We observed significant increases in RV wall thickness in HIV Tg rats compared with controls, both histologically and by echocardiograph measurement. HIV Tg rats also show increased thickening of the pulmonary artery and remodeling of small pulmonary arteries, as well as altered expression of gene pathways associated with PAH. These data represent the first analysis of PAH in HIV Tg rats and suggest that this model will be useful for investigating pathways and identifying potential therapies for HIV-PAH. 相似文献
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Characterization of a cis-Acting Sequence in the pol Region Required To Transfer Human Foamy Virus Vectors 总被引:2,自引:0,他引:2 下载免费PDF全文
Martin Heinkelein Michael Schmidt Nicole Fischer Astrid Moebes Dirk Lindemann Jrg Enssle Axel Rethwilm 《Journal of virology》1998,72(8):6307-6314
To identify cis-acting elements in the foamy virus (FV) RNA pregenome, we developed a transient-vector-production system based on cotransfection of indicator gene-bearing vector and gag-pol and env expression plasmids. Two elements which were critical for vector transfer were found and mapped approximately. The first element was located in the RU5 leader and the 5′ gag region (approximately up to position 650 of the viral RNA). The second element was located in an approximately 2-kb sequence in the 3′ pol region. Although small 5′ and 3′ deletions, as well as internal deletions of the latter element, were tolerated, both elements were found to be absolutely required for vector transfer. The functional characterization of the pol region-located cis-acting element revealed that it is essential for efficient incorporation or the stability of particle-associated virion RNA. Furthermore, virions derived from a vector lacking this sequence were found to be deficient in the cleavage of the Gag protein by the Pol precursor protease. Our results suggest that during the formation of infectious virions, complex interactions between FV Gag and Pol and the viral RNA take place. 相似文献
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Background
MicroRNAs (miRNAs) are highly conserved, short (18–22 nts), non-coding RNA molecules that regulate gene expression by binding to the 3′ untranslated regions (3′UTRs) of mRNAs. While numerous cellular microRNAs have been associated with the progression of various diseases including cancer, miRNAs associated with retroviruses have not been well characterized. Herein we report identification of microRNA-like sequences in coding regions of several HIV-1 genomes.Results
Based on our earlier proteomics and bioinformatics studies, we have identified 8 cellular miRNAs that are predicted to bind to the mRNAs of multiple proteins that are dysregulated during HIV-infection of CD4+ T-cells in vitro. In silico analysis of the full length and mature sequences of these 8 miRNAs and comparisons with all the genomic and subgenomic sequences of HIV-1 strains in global databases revealed that the first 18/18 sequences of the mature hsa-miR-195 sequence (including the short seed sequence), matched perfectly (100%), or with one nucleotide mismatch, within the envelope (env) genes of five HIV-1 genomes from Africa. In addition, we have identified 4 other miRNA-like sequences (hsa-miR-30d, hsa-miR-30e, hsa-miR-374a and hsa-miR-424) within the env and the gag-pol encoding regions of several HIV-1 strains, albeit with reduced homology. Mapping of the miRNA-homologues of env within HIV-1 genomes localized these sequence to the functionally significant variable regions of the env glycoprotein gp120 designated V1, V2, V4 and V5.Conclusions
We conclude that microRNA-like sequences are embedded within the protein-encoding regions of several HIV-1 genomes. Given that the V1 to V5 regions of HIV-1 envelopes contain specific, well-characterized domains that are critical for immune responses, virus neutralization and disease progression, we propose that the newly discovered miRNA-like sequences within the HIV-1 genomes may have evolved to self-regulate survival of the virus in the host by evading innate immune responses and therefore influencing persistence, replication and/or pathogenicity. 相似文献6.
Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in immune response changes, alterations in immunological phenotypes, and ultimately increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV-1 disease, particularly in aging individuals, the HIV-1 transgenic (HIV-1Tg) rat model was utilized. HIV-1Tg rats were challenged with lipopolysaccharide (LPS) to determine immunological alterations during the aging process. LPS is known to cause an imbalance in cytokine and chemokine release, and provides a method to identify changes in immune responses to bacterial infection in an HIV animal model. An immune profile and accompanying cellular consequences as well as changes in inflammatory cytokine and chemokine release related to age and genotype were assessed in HIV-1Tg rats. The percentage of T cells decreased with age, particularly T cytotoxic cells, whereas T helper cells increased with age. Neutrophils and monocytes increased in HIV-1Tg rats during maturation compared to age-matched F344 control rats. Aging HIV-1Tg rats displayed a significant increase in the pro-inflammatory cytokines, IL-6 and TNF-α, along with an increase in the chemokine, KC/GRO, in comparison to age-matched controls. Our data indicate that immunophenotype and immune responses can change during aging in HIV-positive individuals. This information could be important in determining the most beneficial age-dependent therapeutic treatment for HIV patients. 相似文献
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Ricardo Soto-Rifo Paulina S. Rubilar Théophile Ohlmann 《Nucleic acids research》2013,41(12):6286-6299
Here, we show a novel molecular mechanism promoted by the DEAD-box RNA helicase DDX3 for translation of the HIV-1 genomic RNA. This occurs through the adenosine triphosphate-dependent formation of a translation initiation complex that is assembled at the 5′ m7GTP cap of the HIV-1 mRNA. This is due to the property of DDX3 to substitute for the initiation factor eIF4E in the binding of the HIV-1 m7GTP 5′ cap structure where it nucleates the formation of a core DDX3/PABP/eIF4G trimeric complex on the HIV-1 genomic RNA. By using RNA fluorescence in situ hybridization coupled to indirect immunofluorescence, we further show that this viral ribonucleoprotein complex is addressed to compartmentalized cytoplasmic foci where the translation initiation complex is assembled. 相似文献
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William C. Reid Rafael Casas Georgios Z. Papadakis Siva Muthusamy Dianne E. Lee Wael G. Ibrahim Anand Nair Deloris Koziol Dragan Maric Dima A. Hammoud 《PloS one》2016,11(3)
Motor and behavioral abnormalities are common presentations among individuals with HIV-1 associated neurocognitive disorders (HAND). We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era. 相似文献
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Margaret R. Lentz Kristin L. Peterson Wael G. Ibrahim Dianne E. Lee Joelle Sarlls Martin J. Lizak Dragan Maric William C. Reid Dima A. Hammoud 《PloS one》2014,9(8)