Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Due to the worldwide AIDS pandemic, HIV-1 has become the major factor for central nervous system (CNS) diseases. Two major disorders of the CNS caused by HIV-1 have been described, a meningoencephalitis which occurs in 30-50% of patients early after infection and the AIDS dementia complex (ADC, also known as HIV-associated dementia) which is characterized by a predominantly subcortical dementia. The pathophysiology of these clinical syndromes still remains an enigma. However, since monocytes/macrophages may represent the major place of virus replication in the CNS, a hematogenous invasion of HIV-1 into the brain may be crucial to the neuropathogenesis of ADC. One of the most valuable animal models for the study of neuro-AIDS is the infection of macaque monkeys with the simian immunodeficiency virus (SIV). In about 50% of infected rhesus monkeys with an AIDS-like disease, neuropathological lesions similar to ADC in men have been observed. This animal model contributes to our understanding of the mechanisms of viral neuroinvasion early after infection and in the development of neurological disease. In this review we will summarize the state of the art and will focus on further questions concerning the neuropathogenesis of HIV/SIV.
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PMID:Infection of macaque monkeys with simian immunodeficiency virus: an animal model for neuro-AIDS. 945 Feb 28

Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats that causes a spectrum of diseases remarkably similar to AIDS in HIV-infected humans. As part of this spectrum, both HIV-1 and FIV induce neurologic disorders. Because astrocytes are essential in maintaining the homeostasis of the central nervous system, we analyzed FIV for the ability to infect feline astrocytes. Through immunocytochemistry and reverse transcriptase activity, it was demonstrated that two molecular clones of FIV (FIV-34TF10 and FIV-PPR) produce a chronic low level productive infection of feline astrocyte cultures. To investigate the consequences of this infection, selected astrocyte functions were examined. Infection with FIV-34TF10 significantly decreased the ability of astrocytes to scavenge extracellular glutamate (with a peak inhibition of 74%). The effects of the infection did not appear to be a result of toxicity but rather were more selective in nature because the glucose uptake function of the infected astrocyte cultures was not altered. Our data demonstrate that FIV productively infected, at a low level, feline astrocyte cultures, and as a consequence of this infection, an important astroglial function was altered. These findings suggest that a chronic low grade infection of astrocytes may impair the ability of these cells to maintain homeostasis of the central nervous system that, in turn, may contribute to a neurodegenerative disease process that is often associated with lentivirus infections.
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PMID:Effects of feline immunodeficiency virus on astrocyte glutamate uptake: implications for lentivirus-induced central nervous system diseases. 948 37

Although herpes simplex encephalitis (HSE) is not regarded as an opportunistic infection, the occurrence of HSE in immunocompromised patients has been documented and the suggestion made that unusual clinical and neuropathologic features characterize the disorder in this population. To further characterize HSE as it affects the immunodeficient, the authors reviewed the clinical and pathological findings in three immunocompromised patients with autopsy-proven HSE. Two patients had cancer (one with lymphoma and another with glioblastoma multiforme), one was known to be human immunodeficiency virus-type 1 (HIV-1)-seropositive and a second was suspected of harboring underlying HIV-1 infection. Two were receiving dexamethasone at onset of HSE. All had fever, mental status changes and new, focal neurological deficits or worsening of established deficits. Cerebrospinal fluid (CSF) pleocytosis was absent or minimal and head computerized tomographic (CT) scans, performed in all cases, were unrevealing. No patient was clinically suspected of having HSE, only one received acyclovir (for concurrent mucocutaneous herpes) and HSE played a major role in all deaths. Autopsy revealed an unusual form of HSE characterized by a noninflammatory, pseudoischemic histological presentation and the unexpected persistence of viral antigens in abundance despite survival beyond the clinical stage during which inflammatory responses usually peak and productive brain infection wanes. The incidence of HSE in the immunocompromised may be underestimated. Preexistent neurological disease, a noninflammatory CSF profile and negative CT scan may confound the diagnosis in this population, a typical clinical presentation notwithstanding. Increased clinical suspicion, the use of magnetic resonance imaging and polymerase chain reaction analysis of CSF for herpes simplex virus nucleic acid sequences may permit more rapid diagnosis and treatment. The absence of inflammatory infiltrates in some fatal cases of HSE suggests that an intact immune response is not requisite to the devastating neurological injury characteristic of this disorder.
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PMID:Herpes simplex encephalitis (HSE) and the immunocompromised: a clinical and autopsy study of HSE in the settings of cancer and human immunodeficiency virus-type 1 infection. 949 20

Although the mechanisms of human immunodeficiency virus (HIV) neuroinvasion, neuronal injury, and subsequent development of HIV-1-associated AIDS dementia complex are not fully understood, a correlation between monocyte/macrophage infiltrates in the brain and neurological disease exists. In light of the many potential roles that chemokines and chemokine receptors may play in HIV neuropathogenesis, we sought to describe their pattern of expression in the SIV-infected rhesus macaque model of HIV encephalitis. We previously demonstrated elevated expression of the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, and interferon-inducible protein (IP)-10 in brain of macaque monkeys with SIV encephalitis. In this study, we demonstrate that the corresponding chemokine receptors CCR3, CCR5, CXCR3, and CXCR4 are expressed in perivascular infiltrates in these same tissues. In addition, we detected CCR3, CCR5, and CXCR4 on subpopulations of large hippocampal and neocortical pyramidal neurons and on glial cells in both normal and encephalitic brain. These findings suggest that multiple chemokines and their receptors contribute to monocyte and lymphocyte recruitment to the brain in SIV encephalitis. Furthermore, the expression of known HIV/SIV co-receptors on neurons suggests a possible mechanism whereby HIV or SIV can directly interact with these cells, disrupting their normal physiological function and contributing to the pathogenesis of AIDS dementia complex.
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PMID:Chemokine receptor expression on resident and inflammatory cells in the brain of macaques with simian immunodeficiency virus encephalitis. 950 6

Patients with HIV infection are at risk for neurologic complications that can arise through various means. Nervous system disorders sometimes occur as a direct consequence of the HIV infection itself. Or, as immunodeficiency progresses, patients can become susceptible to numerous opportunistic infections and other conditions that have neurologic involvement. Even the antiviral drugs used to treat HIV infection can induce neurologic manifestations. Dr Rachlis discusses several of these manifestations and their management.
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PMID:Neurologic manifestations of HIV infection. Using imaging studies and antiviral therapy effectively. 951 35

A nested polymerase chain reaction (PCR) assay was used to determine the levels of cytomegalovirus (CMV) genomes in cells of CSF from 19 patients with AIDS and 12 human immunodeficiency virus type I (HIV-1) seronegative individuals with various neurologic disorders. Five AIDS patients had autopsy-proven CMV encephalitis (CMVE) and 14 patients had no evidence of CMV-related CNS manifestations. CSF cells from AIDS patients with confirmed CMVE harbored viral genomes at a median value of 3,333/10(5) cells (range, 1,667 to 5,333/10(5) cells; mean, 3,558/10(5) cells) compared with a median value of 125/10(5) cells (range, 9 to 1,000/10(5) cells; mean, 281/10(5) cells) for AIDS patients with CMV-unrelated symptoms and a median value of 1.9/10(5) cells (range, 0 to 562/10(5) cells; mean, 52/10(5) cells) for HIV-1 seronegative control subjects. A subset of CSF samples was assessed using a modified single round amplification PCR with a detection limit of 500 viral copies. CMV DNA was detected in all four specimens from AIDS patients with proven CMVE, in two of five AIDS patients without CMVE, and in none of five seronegative control subjects. Quantitation of CMV genomes in CSF cells is indicative of latent or productive CMV infection and is a reliable means for diagnosis of CMVE in patients with AIDS. Detection of a cutoff value of cellular CMV genomes by means of nonquantitative PCR may identify patients at risk for CMV infection of the CNS.
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PMID:Diagnosis of cytomegalovirus encephalitis in patients with AIDS by quantitation of cytomegalovirus genomes in cells of cerebrospinal fluid. 952 Dec 58

Productive replication of human immunodeficiency virus type 1 (HIV-1) in brain macrophages and microglia is a critical component of viral neuropathogenesis. However, how virus-macrophage interactions lead to neurological disease remains incompletely understood. Possibly, a differential ability of virus to replicate in brain tissue macrophages versus macrophages in other tissues underlies HIV-1 neurovirulence. To these ends, we established systems for the isolation and propagation of pure populations of human microglia and then analyzed the viral life cycles of divergent HIV-1 strains in these cells and in cultured monocytes by using identical viral inocula and indicator systems. The HIV-1 isolates included those isolated from blood, lung tissue, cerebrospinal fluids (CSF), and brain tissues of infected subjects: HIV-1(ADA) and HIV-1(89.6) (from peripheral blood mononuclear cells), HIV-1(DJV) and HIV-1(JR-FL) (from brain tissue), HIV-1(SF162) (from CSF), and HIV-1(BAL) (from lung tissue). The synthesis of viral nucleic acids and viral mRNA, cytopathicity, and release of progeny virions were assessed. A significant heterogeneity among macrophage-tropic isolates for infection of monocytes and microglia was demonstrated. Importantly, a complete analysis of the viral life cycle revealed no preferential differences in the abilities of the HIV-1 strains tested to replicate in microglia and/or monocytes. Macrophage tropism likely dictates the abilities of HIV-1 to invade, replicate, and incite disease within its microglial target cells.
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PMID:Human immunodeficiency virus neurotropism: an analysis of viral replication and cytopathicity for divergent strains in monocytes and microglia. 952 61

The question of whether consensus nucleotide substitutions in the long terminal repeat (LTR) region of simian immunodeficiency virus strain mac (SIVmac) are important for neurovirulence was investigated in this report. Brains and lymph nodes from two macaques that developed AIDS and encephalitis following inoculation with two strains of neurovirulent SIVmac, and from one animal with AIDS but no neurological disease after inoculation with non-neurovirulent SIVmac239 were used. The 5' LTR regions from neurovirulent SIVmacR71/17E and SIVmac7F-Lu were amplified, cloned and sequenced and these sequences were compared to the LTRs amplified from three regions of the respective encephalitic brains and lymph nodes from macaques inoculated with each virus. The SIVmac7F-Lu and SIVmacR71/17E viruses had zero and three consensus substitutions, respectively, in the U3, R and U5 regions of the LTR compared to that of SIVmac239. The only consensus substitution in the LTR-gag region of the genome was a T to C change at position 829 within the tRNA binding site. The sequences amplified from the brain and lymph nodes of the two animals with AIDS and encephalitis were identical. This single common substitution in this region of the virus genome, the T to C substitution at position 829, was also found in the LTRs isolated from the brain and lymphoid organs from the macaque inoculated with SIVmac239. The virtual identity in nucleotide sequences in the LTR of the neurovirulent and non-neurovirulent viruses and in CNS and lymph tissues of animals inoculated with the viruses suggests that the LTR has no effect on the tissue tropisms of the viruses.
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PMID:Nucleotide substitutions in the long terminal repeat are not required for development of neurovirulence by simian immunodeficiency virus strain mac. 960 23

Feline immunodeficiency virus (FIV) is a lentivirus that causes immune suppression and neurological disease in cats. Among animal viruses, individual viral strains have been shown to be neurovirulent, but the role of viral strain specificity among lentiviruses and its relationship to systemic immune suppression in the development of neurological disease remains uncertain. To determine the extent to which different FIV strains caused neurological disease, FIV V1CSF and Petaluma were compared in ex vivo assays and in vivo. Both viruses infected and replicated in macrophage and mixed glial cell cultures at similar levels, but V1CSF induced significantly greater neuronal death than Petaluma in a neurotoxicity assay. V1CSF-infected animals showed significant neurodevelopmental delay compared to the Petaluma-infected and uninfected animals. Magnetic resonance spectroscopy studies of frontal cortex revealed significantly reduced N-acetyl aspartate/creatine ratios in the V1CSF group compared to the other groups. Cyclosporin A treatment of Petaluma-infected animals caused neurodevelopmental delay and reduced N-acetyl aspartate/creatine ratios in the brain. Reduced CD4(+) and CD8(+) cell counts were observed in the V1CSF-infected group compared to the uninfected and Petaluma-infected groups. These findings suggest that neurodevelopmental delay and neuronal injury is FIV strain specific but that systemic immune suppression is also an important determinant of FIV-induced neurovirulence.
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PMID:Neurovirulence in feline immunodeficiency virus-infected neonatal cats is viral strain specific and dependent on systemic immune suppression. 976 56

Human immunodeficiency virus-associated dementia (HAD) is associated with increased numbers of activated central nervous system (CNS) macrophages. Chemokines, which regulate infiltration of macrophages, were measured in the cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-negative and HIV-positive individuals with and without neurological disease. Monocyte chemotactic protein (MCP)-1 and RANTES (but not MCP-3), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, or interleukin-8 (IL-8) was higher in HAD. MCP-1 correlated with CSF viral load and severity of dementia, and it increased over time in patients who developed dementia.
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PMID:Beta-chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia. 981 43


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