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]
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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]
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.
Examples of viral inclusion bodies in animals are Intracytoplasmic eosinophilic-
Intranuclear acidophilic-
Intranuclear basophilic-
Both intranuclear and intracytoplasmic-
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].
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:
70-80% of recombinant proteins expressed E. coli are contained in inclusion bodies (i.e., protein aggregates). 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 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]
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