Virus-Induced Autoimmunity: Monoclonal Antibodies That React with Endocrine Tissues

Haspel, Martin V.; Onodera, Takashi; Prabhakar, Bellur S.; Horita, Masakazu; Suzuki, Hoshibumi; Notkins, Abner Louis

doi:10.1126/science.6301002

Cited by 134 publications

(38 citation statements)

References 8 publications

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“…Molecular structure coming to light in the well-studied immune system of vertebrates, for example, favors such interpretation. So too does the growing emphasis on mimicry as a factor in parasitism (29,30,(79)(80)(81)(82)(83)(84)(85)(86)(87)(88). Presumably almost any common, necessary, and exposed molecular structure on or in cells of a host can be potentially mimicked, so bringing the genetics of that structure into play.…”

Section: Preserve or Eliminatementioning

confidence: 99%

Sexual reproduction as an adaptation to resist parasites (a review).

Hamilton

Axelrod²,

Tanese³

1990

Proc. Natl. Acad. Sci. U.S.A.

1,153

929

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Darwinian theory has yet to explain adequately the fact of sex. If males provide little or no aid to offspring, a high (up to 2-fold) extra average fitness has to emerge as a property of a sexual parentage if sex is to be stable. The advantage must presumably come from recombination but has been hard to identify. It may well lie in the necessity to recombine defenses to defeat numerous parasites. A model demonstrating this works best for contesting hosts whose defense polymorphisms are constrained to low mutation rates.A review of the literature shows that the predictions of parasite coevolution fit well with the known ecology of sex. Moreover, parasite coevolution is superior to previous models of the evolution of sex by supporting the stability of sex under the following challenging conditions: very low fecundity, realistic patterns of genotype fitness and changing environment, and frequent mutation to parthenogenesis, even while sex pays the full 2-fold cost.Parasite coevolution will be shown to be superior to previous models of the evolution of sex by supporting the stability of sex under the following challenging conditions.

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Section: Preserve or Eliminatementioning

confidence: 99%

Sexual reproduction as an adaptation to resist parasites (a review).

Hamilton

Axelrod²,

Tanese³

1990

Proc. Natl. Acad. Sci. U.S.A.

1,153

929

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“…Interestingly, in most cases, several different viruses have been proposed as etiologic agents of the same disease. Experimental data have suggested that viruses trigger an autoimmune humoral response by distinct mechanisms, including polyclonal B-lymphocyte activation, antigenic mimicry, modification of self-antigen, production of anti-idiotypic antibodies, or enhancement of major histocompatibility complex molecule expression on potential antigen-presenting cells (4,9,11,15,20,25,31,37). However, although it has been conclusively shown in several models that autoantibody secretion was triggered by infection, the actual pathogenicity of these antibodies has not always been demonstrated.…”

mentioning

confidence: 99%

Exacerbation of Autoantibody-Mediated Hemolytic Anemia by Viral Infection

Meité

Léonard

Idrissi

et al. 2000

J Virol

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Strong enhancement of the pathogenicity of an antierythrocyte monoclonal antibody was observed after infection of mice with lactate dehydrogenase-elevating virus. While injection of the antierythrocyte antibody alone induced only moderate anemia, concomitant infection with this virus, which is harmless in most normal mice, led to a dramatic drop in the hematocrit and to death of infected animals. In vitro and in vivo analyses showed a dramatic increase in the ability of macrophages from infected mice to phagocytose antibody-coated erythrocytes. These results indicate that viruses can trigger the onset of autoimmune disease by enhancing the pathogenicity of autoantibodies. They may explain how unrelated viruses could be implicated in the etiology of autoantibody-mediated autoimmune diseases.A causal connection between viral infection and the development of clinical pathology has long been suspected for a number of autoimmune diseases mediated by autoantibodies (reviewed in reference 36). Interestingly, in most cases, several different viruses have been proposed as etiologic agents of the same disease. Experimental data have suggested that viruses trigger an autoimmune humoral response by distinct mechanisms, including polyclonal B-lymphocyte activation, antigenic mimicry, modification of self-antigen, production of anti-idiotypic antibodies, or enhancement of major histocompatibility complex molecule expression on potential antigen-presenting cells (4,9,11,15,20,25,31,37). However, although it has been conclusively shown in several models that autoantibody secretion was triggered by infection, the actual pathogenicity of these antibodies has not always been demonstrated. Similarly, other stimuli, like immunization of mice with rat red blood cells, may lead to autoantibody production without development of the corresponding disease, in this case, hemolytic anemia (8,24,34). Therefore, it may be that mere autoantibody secretion is not sufficient to trigger an autoimmune disease and that the immune environment of the host plays an important role in the pathogenicity of such autoantibodies.Viruses have also been shown to variably affect macrophage functions, including cytokine production and the ability to present antigens (6, 16). Since it is known that some autoantibody-mediated diseases involve phagocytosis by macrophages, we postulated that modulation of this cellular function may explain the induction of such clinical diseases observed in the course of viral infections. To test this hypothesis, we used an experimental model of anemia induced by administration of antierythrocyte monoclonal antibodies (29). Our results indicate that a viral infection with lactate dehydrogenase-elevating virus (LDV) may trigger a dramatic hemolytic disease by enhancing the pathogenicity of autoantibodies. If confirmed with other models, this observation may indicate how different viruses can trigger similar clinical autoimmune diseases and open the way to novel therapeutic approaches. MATERIALS AND METHODSMice. Female BALB/c mice w...

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“…Type 1, when injected into newborn mice, infects ependymal tissue and causes hydrocephalus (9), whereas type 3 infects neurons and causes a rapidly fatal encephalitis (10). Both types 1 and 3 reovirus can also infect cells ofthe endocrine pancreas and may cause diabetes (11)(12)(13). Type 1 also produces an autoimmune syndrome associated with growth retardation (14).…”

Section: Introductionmentioning

confidence: 99%

Ammonium inhibits processing and cytotoxicity of reovirus, a nonenveloped virus.

Maratos–Flier¹,

Goodman²,

Murray³

et al. 1986

J. Clin. Invest.

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Successful viral infection involves a series of interactions between the virus and the host cell. The outcome of viral infection is, in fact, dependent on intact cellular function; it is required for viral binding, internalization, and uncoating. To determine the potential importance of lysosomal processing on the outcome of infection with a nonenveloped virus, we have studied the effects of NILCI on the course of reovirus infection on a beta-cell tumor in culture.Addition of 10 mM NH4CI to the medium inhibited viral growth by >80% and reduced toxic effects of the virus on cell viability, protein, and DNA synthesis by 3045%. In addition, synthesis of viral proteins was markedly decreased. Uptake of virus preiabeled with V35Simethionine was not affected by the ammonium; however, cleavage of ,ulC, an outer capsid protein of the virus wliose cleavage appears to be required for viral replication, was delayed. These results suggest that intracellular processing of reovirus is dependent on a lysosomal pathway and that disruption of this pathway can alter the course of viral infection.

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Virus-Induced Autoimmunity: Monoclonal Antibodies That React with Endocrine Tissues

Cited by 134 publications

References 8 publications

Sexual reproduction as an adaptation to resist parasites (a review).

Sexual reproduction as an adaptation to resist parasites (a review).

Exacerbation of Autoantibody-Mediated Hemolytic Anemia by Viral Infection

Ammonium inhibits processing and cytotoxicity of reovirus, a nonenveloped virus.

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