HIV disorders of the brain; pathology and pathogenesis

Valle, Luis Del; Piña‐Oviedo, Sergio

doi:10.2741/1830

Cited by 92 publications

(70 citation statements)

References 118 publications

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“…Based on these observations, we performed immunohistochemical experiments in cases of HIV encephalitis (HIVE) to determine the presence and cellular location of HIV-1 proteins. All cases of HIVE were characterized according to established standards (40) and presented perivascular cuff of inflammatory cells, including giant multinucleated cells (Fig. 1B, panel a), parenchymal microglial nodules (panel b), and reactive astrocytes (panel c).…”

Section: Detection Of Hiv-1 Proteins P24 and Tat In Human Brainmentioning

confidence: 99%

HIV-1 Tat Protein Promotes Neuronal Dysfunction through Disruption of MicroRNAs

Chang

Mukerjee

Bagashev

et al. 2011

Journal of Biological Chemistry

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Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release from the infected cells and taken up by noninfected cells. Using microRNA array assay, we demonstrated that Tat deregulates the levels of several miRNAs. Interestingly, miR-34a was among the most highly induced miRNAs in Tat-treated neurons. Tat also decreases the levels of miR-34a target genes such as CREB protein as shown by real time PCR. The effect of Tat was neutralized in the presence of anti-miR-34a. Using in situ hybridization assay, we found that the levels of miR-34a increase in Tat transgenic mice when compared with the parental mice. Therefore, we conclude that deregulation of neuronal functions by HIV-1 Tat protein is miRNA-dependent.

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Section: Detection Of Hiv-1 Proteins P24 and Tat In Human Brainmentioning

confidence: 99%

HIV-1 Tat Protein Promotes Neuronal Dysfunction through Disruption of MicroRNAs

Chang

Mukerjee

Bagashev

et al. 2011

Journal of Biological Chemistry

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“…We demonstrate that the presence of agnoprotein sensitizes differentiating oligodendrocyte progenitors to an exogenous source of ROS, since the treatment of CG-4 cells with the H 2 O 2 oxidant resulted in extensive DNA breakage in agnopositive cells. One of the important histological features of PML lesions is the presence of microglial nodules (21). Activated microglia release ROS that cause neurotoxicity and white matter injury (12,41).…”

Section: Discussionmentioning

confidence: 99%

“…The histological hallmarks of white matter from PML patients include the appearance of oligodendrocytes with enlarged hyperchromatic nuclei that contain inclusion bodies shaped by crystalline arrays of JCV particles and astrocytes with bizarre nuclei and mitotic figures (21,35). The presence of virions has also been demonstrated among lamellae of the myelin sheath of a viable axon (47).…”

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confidence: 99%

JC Virus Agnoprotein Inhibits In Vitro Differentiation of Oligodendrocytes and Promotes Apoptosis

Merabova

Kaniowska

Kaminski

et al. 2008

J Virol

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Productive infection of oligodendrocytes, which are responsible for the formation of myelin sheath in the central nervous system, with the human neurotropic virus JC virus (JCV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). In addition to encoding T antigen and the capsid proteins, which are produced at the early and late phases of the infection cycle, respectively, JCV encodes a small regulatory protein named agnoprotein that is important for successful completion of the virus life cycle. Here we used bipotential CG-4 cells to examine the impact of agnoprotein on oligodendrocyte differentiation and survival in the absence of JCV lytic infection. We demonstrate that the expression of agnoprotein delayed the formation of complex outgrowth networks of the cells during oligodendrocyte differentiation. These alterations were accompanied by high levels of DNA damage, induction of proapoptotic proteins, and suppression of prosurvival signaling. Accordingly, apoptosis was significantly increased upon the induction of CG-4 cells toward differentiation in cells expressing agnoprotein. These observations provide the first evidence for the possible involvement of agnoprotein, independent from its role in viral replication, in a series of biological events that may contribute to the pathological features seen in PML lesions.First exposure to the human polyomavirus JC virus (JCV) commonly occurs during childhood and results in a subclinical outcome. Reactivation of the initially latent virus in individuals with impaired immune systems results in the development of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) (9,31,35). PML manifests clinically with signs of neurological deficits of various degrees, including weakness, visual deficits, and cognitive abnormalities. PML is mainly associated with advanced human immunodeficiency virus (HIV)-induced diseases and AIDS (8, 9), lymphoproliferative or myeloproliferative diseases, malignancies, and rheumatic disorders treated with corticosteroids and cytotoxic drugs (1,16,25,34,39,52,58,71,75,77). Recently, PML has also been diagnosed in patients with multiple sclerosis and Crohn's disease receiving natalizumab (37,40,42,74), a humanized monoclonal antibody that binds to the ␣4 subunit of ␣4␤1 and ␣4␤7 integrins and inhibits the trafficking of leukocytes across the blood-brain barrier.The histological hallmarks of white matter from PML patients include the appearance of oligodendrocytes with enlarged hyperchromatic nuclei that contain inclusion bodies shaped by crystalline arrays of JCV particles and astrocytes with bizarre nuclei and mitotic figures (21, 35). The presence of virions has also been demonstrated among lamellae of the myelin sheath of a viable axon (47). In cell culture systems, JCV efficiently infects primary cultures of human brain containing oligodendrocytes and astrocytes. Recent studies have shown that JCV can infect multipotential human central nervous system progenitor cells isolated fro...

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“…Congenital abnormalities in humans, such as microcephaly, hydrocephaly, chorioretinitis, convulsion, cerebral calcification, epilepsy, blindness, deafness, and mental retardation may occur if the mother acquires infection during pregnancy [5]. In addition to congenital anomalies, T. gondii also causes severe neuropathologic infections in immunocompromised hosts, such as AIDS and cancer patients receiving chemotherapy [6].…”

Section: Introductionmentioning

confidence: 99%

Seroprevalence and risk factors for toxoplasmosis in large ruminants in northern Punjab, Pakistan

Ahmad

Qayyum

2014

J Infect Dev Ctries

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Introduction: Toxoplasmosis is a widespread zoonosis that causes significant economic losses due to abortions and other developmental disabilities in livestock animals. The objectives of the current study were to determine the prevalence and associated risk factors of Toxoplasma gondii infection in cattle and buffaloes in northern parts of Punjab, Pakistan, where no such work previously existed. Methodology:Serum samples obtained from 400 cattle and 422 buffaloes present on different private and government-owned farms were tested for anti-Toxoplasma IgG and anti-Toxoplasma IgM antibodies by using enzyme linked immunosorbent assay (ELISA). Additional data, including water sources, hygienic status at the farm, management practices, size of the herd, and presence of cats in the vicinity of the farm were obtained using a questionnaire in surveys and interviews. Results: The overall prevalence of infection was 19.75% (79/400) in cattle and 15.16% (64/422) in buffaloes. IgG antibodies were found in 75 (18.75%) cattle and 58 (13.74%) buffaloes, while IgM antibodies were found in 9 (2.25%) cattle and 10 (2.37%) buffaloes. Seroprevalence was significantly higher in females and older animals of both species. Seroprevalence was found to be associated with poor hygienic conditions, extensive management practices, and presence of cats in the surrounding areas. No difference of seroprevalence was observed with respect to different breeds, location, water source, and herd size. Conclusion: The present study found that T. gondii is prevalent in large ruminants in northern Punjab, and may have important implications for the livestock industry and public health.

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HIV disorders of the brain; pathology and pathogenesis

Cited by 92 publications

References 118 publications

HIV-1 Tat Protein Promotes Neuronal Dysfunction through Disruption of MicroRNAs

HIV-1 Tat Protein Promotes Neuronal Dysfunction through Disruption of MicroRNAs

JC Virus Agnoprotein Inhibits In Vitro Differentiation of Oligodendrocytes and Promotes Apoptosis

Seroprevalence and risk factors for toxoplasmosis in large ruminants in northern Punjab, Pakistan

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