Inclusion body

Inclusion bodies are nuclear or cytoplasmic aggregates of stainable substances, usually proteins. They typically represent sites of viral multiplication in a bacterium or a eukaryotic cell and usually consist of viral capsid proteins. Inclusion bodies can also be hallmarks of genetic diseases, as in the case of Neuronal Inclusion bodies in disorders like Frontotemporal dementia and Parkinson's disease.[1]

Contents

Composition

Protein inclusion bodies are classically thought to contain misfolded protein. However, this has recently been contested, as green fluorescent protein will sometimes fluoresce in inclusion bodies, which indicates some resemblance of the native structure and researchers have recovered folded protein from inclusion bodies.[2][3][4]

Mechanism of formation

When genes from one organism are expressed in another the resulting protein sometimes forms inclusion bodies. This is often true when large evolutionary distances are crossed: a cDNA isolated from Eukarya for example, and expressed as a recombinant gene in a prokaryote risks the formation of the inactive aggregates of protein known as inclusion bodies. While the cDNA may properly code for a translatable mRNA, the protein that results will emerge in a foreign microenvironment. This often has fatal effects, especially if the intent of cloning is to produce a biologically active protein. For example, eukaryotic systems for carbohydrate modification and membrane transport are not found in prokaryotes. The internal microenvironment of a prokaryotic cell (pH, osmolarity) may differ from that of the original source of the gene. Mechanisms for folding a protein may also be absent, and hydrophobic residues that normally would remain buried may be exposed and available for interaction with similar exposed sites on other ectopic proteins. Processing systems for the cleavage and removal of internal peptides would also be absent in bacteria. The initial attempts to clone insulin in a bacterium suffered all of these deficits. In addition, the fine controls that may keep the concentration of a protein low will also be missing in a prokaryotic cell, and overexpression can result in filling a cell with ectopic protein that, even if it were properly folded, would precipitate by saturating its environment.

Viral inclusion bodies

Examples of viral inclusion bodies in animals are Intracytoplasmic eosinophilic-

Intranuclear acidophilic-

Intranuclear basophilic-

Both intranuclear and intracytoplasmic-

  • Warthin finkeldey bodies in Measles

Examples of viral inclusion bodies in plants [1] include aggregations of virus particles (like those for Cucumber mosaic virus [2]) and aggregations of viral proteins (like the cylindrical inclusions of potyviruses [3]). Depending on the plant and the plant virus family these inclusions can be found in epidermal cells, mesophyll cells, and stomatal cells when plant tissue when properly stained [4].

Inclusion bodies in Erythrocytes

Normally a red blood cell does not contain inclusions in the cytoplasm. However, it may be seen because of certain hematologic disorders.

There are three kinds of erythrocyte inclusions:

  1. Developmental Organelles
    1. Howell-Jolly bodies: small, round fragments of the nucleus resulting from karyorrhexis or nuclear disintegration of the late reticulocyte and stain reddish-blue with Wright stain.
    2. Basophilic stipplings - this stipplings is either fine or coarse, deep blue to purple staining inclusion that appears in erythrocytes on a dried Wright stain.
    3. Pappenheimer bodies - are siderotic granules which are small, irregular, dark-staining granules that appear near the periphery of a young erythrocyte in a Wright stain.
    4. Polychromatophilic red cells - young red cells that no longer have nucleus but still contain some RNA.
    5. Cabot Rings - ring-like structure and may appear in erythrocytes in megaloblastic anemia or in severe anemias, lead poisoning, and in dyserythropoiesis, in which erythrocytes are destroyed before being released from the bone marrow.
  2. Abnormal Hemoglobin Precipitation
    1. Heinz bodies - round bodies, refractile inclusions not visible on a Wright stain film. It is best identified by supravital staining with basic dyes.
    2. Hemoglobin H Inclusions - alpha thalassemia, greenish-blue inclusion bodies appear in many erythrocytes after four drops of blood is incubated with 0.5mL of Brilliant cresyl blue for 20 minutes at 37°C.
  3. Protozoan Inclusion
    1. Malaria
    2. Babesia

Current problems with the isolation of proteins from bacterial inclusion bodies

70-80% of recombinant proteins expressed E. coli are contained in inclusion bodies (i.e., protein aggregates).[citation needed] The purification of the expressed proteins from inclusion bodies usually require two main steps: extraction of inclusion bodies from the bacteria followed by the solubilisation of the purified inclusion bodies. This is considered labour-intensive, time consuming and not cost effective.

Pseudo-inclusions

Pseudo-inclusions are invaginations of the cytoplasm into the cell nuclei, which may give the appearance of intranuclear inclusions. They may appear in papillary thyroid carcinoma.[5]

References

  1. ^ Cruts, M; Gijselinck, I, van der Zee, J, Engelborghs, S, Wils, H, Pirici, D, Rademakers, R, Vandenberghe, R, Dermaut, B, Martin, JJ, van Duijn, C, Peeters, K, Sciot, R, Santens, P, De Pooter, T, Mattheijssens, M, Van den Broeck, M, Cuijt, I, Vennekens, K, De Deyn, PP, Kumar-Singh, S, Van Broeckhoven, C (2006-08-24). "Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21.". Nature 442 (7105): 920–4. doi:10.1038/nature05017. PMID 16862115. 
  2. ^ Biochem Biophys Res Com 328(2005) 189-197
  3. ^ Protein Eng 7(1994) 131-136
  4. ^ Biochem Biophys Res Comm 312 (2003) 1383-1386
  5. ^ Chapter 20 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7.  8th edition.

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Look at other dictionaries:

  • inclusion body — n an inclusion, abnormal structure, or foreign cell within a cell specif an intracellular body that is characteristic of some virus diseases and that is the site of virus multiplication …   Medical dictionary

  • inclusion body — n. any of various small particles of nonliving or foreign material occurring in body cells, as a pigment or secretion granule, a microsome, or a virus …   English World dictionary

  • inclusion body — noun any small intracellular body found within another (characteristic of certain diseases) (Freq. 1) an inclusion in the cytoplasm of the cell • Syn: ↑cellular inclusion, ↑inclusion • Hypernyms: ↑body • Hyponyms …   Useful english dictionary

  • inclusion body — noun Date: 1913 an inclusion, abnormal structure, or foreign cell within a cell (as the eosinophilic body formed by a cytomegalovirus or the abnormal filament characteristic of some myopathies) …   New Collegiate Dictionary

  • inclusion body — Pathol. a particle that takes a characteristic stain, found in a virus infected cell. [1920 25] * * * …   Universalium

  • inclusion body — /ɪnˈkluʒən bɒdi/ (say in kloohzhuhn bodee) noun a particle which takes a characteristic stain, found in a virus infected cell nucleus or cytoplasm …   Australian English dictionary

  • inclusion body — A protein that is overproduced in a recombinant bacterium and forms a crystalline structure inside the bacterial cell …   Glossary of Biotechnology

  • Inclusion body myositis — Classification and external resources ICD 10 M60.8 [1] ICD 9 …   Wikipedia

  • inclusion body encephalitis — noun a rare chronic progressive encephalitis caused by the measles virus and occurring primarily in children and young adults; death usually occurs within three years; characterized by primary measles infection before the age of two years • Syn:… …   Useful english dictionary

  • inclusion body hepatitis — a viral disease of young chickens, caused by an adenovirus and characterized by hemorrhage, jaundice, and anemia; hepatocytes have eosinophilic inclusion bodies. Mortality in a flock may reach 25 per cent …   Medical dictionary


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