Molecular Mimicry Accompanying HIV-1 Infection: Human Monoclonal Antibodies That Bind to gp41 and to Astrocytes

Eddleston, Michael; Torre, Juan Carlos de la; Xu, Jian-Yin; Dorfman, N. A.; Notkins, A L; Zolla‐Pazner, Susan; Oldstone, Michael B. A.

doi:10.1089/aid.1993.9.939

Cited by 23 publications

(9 citation statements)

References 35 publications

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“…Astrocytes are the most common cell type in the brain and play a key role in maintaining the appropriate microenvironment in the CNS required for normal neuronal activity (3,27). One of the most important functions of astrocytes is to regulate the level of extracellular glutamate, a major excitatory neurotransmitter (64).…”

Section: Discussionmentioning

confidence: 99%

Borna Disease Virus Persistence Causes Inhibition of Glutamate Uptake by Feline Primary Cortical Astrocytes

Billaud

Phillips

et al. 2000

J Virol

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Borna disease virus (BDV), a nonsegmented, negative-stranded (NNS) RNA virus, causes central nervous system (CNS) disease in a broad range of vertebrate species, including felines. Both viral and host factors contribute to very diverse clinical and pathological manifestations associated with BDV infection. BDV persistence in the CNS can cause neurobehavioral and neurodevelopmental abnormalities in the absence of encephalitis. These BDV-induced CNS disturbances are associated with altered cytokine and neurotrophin expression, as well as cell damage that is very restricted to specific brain regions and neuronal subpopulations. BDV also targets astrocytes, resulting in the development of prominent astrocytosis. Astrocytes play essential roles in maintaining CNS homeostasis, and disruption of their normal activities can contribute to altered brain function. Therefore, we have examined the effect of BDV infection on the astrocyte's physiology. We present here evidence that BDV can establish a nonlytic chronic infection in primary cortical feline astrocytes that is associated with a severe impairment in the astrocytes' ability to uptake glutamate. In contrast, the astrocytes' ability to uptake glucose, as well as their protein synthesis, viability, and rate of proliferation, was not affected by BDV infection. These findings suggest that, in vivo, BDV could also affect an important astrocyte function required to prevent neuronal excitotoxicity. This, in turn, might contribute to the neuropathogenesis of BDV.Borna disease (BD) virus (BDV) causes central nervous system (CNS) disease in a broad range of vertebrate species (36,43,48,63,65). BDV has a nonsegmented, negative-strand (NNS) RNA genome (9, 17). Based on its unique genetic and biological features, BDV is considered to be the prototypic member of a new virus family, Bornaviridae, within the order Mononegavirales (19,68).Naturally occurring BDV infections were thought to be mainly restricted to horses and sheep within certain geographic regions of central Europe. Current evidence, however, indicates that the natural host range, geographic distribution, and prevalence of BDV are much broader than previously considered (36,43,63,65). The genetics, immune status, and age of the host, as well as viral factors, contribute to a high degree of heterogeneity in disease symptoms and pathological manifestations associated with BDV infection. Clinical manifestations can range from dramatic to subtle or even been unapparent (32,36,43,63,65). Nevertheless, all known BDV isolates are noncytolytic and highly neurotropic (43,48,65). Heightened viral gene expression in limbic system structures and neuronal structural alterations within the hippocampal formation are the main histopathological hallmarks of BDV infection (32,34,35). Immune cell infiltrates are frequently, but not always, observed in the CNS of BDV-infected animals, and immunemediated neuronal damage is thought to be responsible for the clinical symptoms associated with classic BD (5,48,65,71). BDV affects the postnata...

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Section: Discussionmentioning

confidence: 99%

Borna Disease Virus Persistence Causes Inhibition of Glutamate Uptake by Feline Primary Cortical Astrocytes

Billaud

Phillips

et al. 2000

J Virol

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“…However, the neural cells in the CNS appear to be not or only slightly susceptible to infection with HIV-I (Sharpless et al, 1992), so direct cytopathic effects alone cannot account for the neurological damage. One hypothesis to explain the neuropathological effect proposes that molecular mimicry of HIV and proteins in the brain results in an autoimmune reaction with ensuing tissue damage (Trujillo e t al., 1993;Eddleston et al, 1993). In the brain, the primary targets of HIV-1 seem to be microglial/macrophage cells (Koenig et al, 1986;Watkins et al, 1990;Wiley et al, 1986).…”

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confidence: 99%

Differences in human immunodeficiency virus type 1 V3 sequences from patients with and without AIDS dementia complex

Kuiken

Goudsmit²,

Weiller³

et al. 1995

Journal of General Virology

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Paired serum and cerebrospinal fluid (CSF) samples from 10 AIDS patients with and 10 without AIDS dementia complex (ADC) were studied, in an attempt to uncover ADC-associated variation in V3 sequences. Sequences were obtained from four of the patients with and eight of those without ADC. Comparison of the sequences using a resampling technique revealed a significant ADC-associated difference occurring at several amino acid positions. Results from serum and CSF sequences were comparable. These differences may indicate that the virus found in ADC and that in non-ADC patients have different biological properties. Comparison of serum versus CSF sequences within samples from both ADC and non-ADC patients, using the same resampling technique, revealed no clear distinctions. In some patients, the sequence populations in serum and CSF were completely distinct, while in others, there was no difference in distribution. These patterns were not associated with ADC.

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“…As previously reported, monoclonal antibodies that bound to HIV-1 gp41 and cross-reacted with astrocytes were recovered from the blood of patients infected with HIV-1 (31). Such mimicry by antiviral antibodies interacting with an astrocyte isoform of alpha actinin (32) could play a role in the dementia of AIDS patients.…”

Section: Discussionmentioning

confidence: 74%

Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy

García-Vallejo

Domínguez

Tamayo

2005

Braz J Med Biol Res

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Viruses share antigenic sites with normal host cell components, a phenomenon known as molecular mimicry. It has long been suggested that viral infections might trigger an autoimmune response by several mechanisms including molecular mimicry. More than 600 antiviral monoclonal antibodies generated against 11 different viruses have been reported to react with 3.5% of cells specific for uninfected mouse organs. The main pathological feature of tropical spastic paraparesis/ human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (TSP/HAM) is a chronic inflammation of the spinal cord characterized by perivascular cuffing of mononuclear cells accompanied by parenchymal lymphocytic infiltration. We detected the presence of autoantibodies against a 98-to 100-kDa protein of in vitro cultured human astrocytes and a 33-to 35-kDa protein from normal human brain in the serum of HTLV-I-seropositive individuals. The two cell proteins exhibited molecular mimicry with HTLV-I gag and tax proteins in TSP/HAM patients, respectively. Furthermore, the location of 33-to 35-kDa protein cross-reaction correlated with the anatomical spinal cord areas (in the rat model) in which axonal damage has been reported in several cases of TSP/HAM patients. Our experimental evidence strongly suggests that the demyelinating process occurring in TSP/ HAM may be mediated by molecular mimicry between domains of some viral proteins and normal cellular targets of the spinal cord sections involved in the neurodegeneration.

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Molecular Mimicry Accompanying HIV-1 Infection: Human Monoclonal Antibodies That Bind to gp41 and to Astrocytes

Cited by 23 publications

References 35 publications

Borna Disease Virus Persistence Causes Inhibition of Glutamate Uptake by Feline Primary Cortical Astrocytes

Borna Disease Virus Persistence Causes Inhibition of Glutamate Uptake by Feline Primary Cortical Astrocytes

Differences in human immunodeficiency virus type 1 V3 sequences from patients with and without AIDS dementia complex

Autoimmunity and molecular mimicry in tropical spastic paraparesis/human T-lymphotropic virus-associated myelopathy

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