Inclusion bodies
Encyclopedia
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
.
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.
Intracytoplasmic eosinophilic-
Intranuclear acidophilic-
Intranuclear basophilic-
Both intranuclear and intracytoplasmic-
Examples of viral inclusion bodies in plants http://plantpath.ifas.ufl.edu/pdc/Inclusionpage/Florvirus.html include aggregations of virus particles (like those for Cucumber mosaic virus http://plantpath.ifas.ufl.edu/pdc/Inclusionpage/CMV/CucMoInc.html) and aggregations of viral proteins (like the cylindrical inclusions of potyviruses http://plantpath.ifas.ufl.edu/pdc/Inclusionpage/Poty/poty.html). 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 http://plantpath.ifas.ufl.edu/pdc/Inclusionpage/Howto.html.
does not contain inclusions in the cytoplasm. However, it may be seen because of certain hematologic disorders.
There are three kinds of erythrocyte inclusions:
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
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
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
proteins. Inclusion bodies can also be hallmarks of genetic diseases, as in the case of Neuronal Inclusion bodies in disorders like Frontotemporal dementia
Frontotemporal dementia
Frontotemporal dementia is a clinical syndrome caused by degeneration of the frontal lobe of the brain and may extend back to the temporal lobe...
and Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
.
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.Mechanism of formation
When genesGênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
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
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
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
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that results will emerge in a foreign microenvironment. This often has fatal effects, especially if the intent of cloning
Cloning
Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...
is to produce a biologically active protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
. For example, eukaryotic systems for carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
modification and membrane transport
Membrane transport
In cellular biology the term membrane transport refers to the collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes namely lipid bilayers that contain proteins embedded in them...
are not found in prokaryotes. The internal microenvironment
Microenvironment
Microenvironment carries different meanings depending on the context.* Medical: a small or relatively small usually distinctly specialized and effectively isolated habitat or environment...
of a prokaryotic cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
(pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
, osmolarity) may differ from that of the original source of the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Mechanisms for folding a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
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
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. The initial attempts to clone insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
in a bacterium suffered all of these deficits. In addition, the fine controls that may keep the concentration of a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
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 areIntracytoplasmic eosinophilic-
- Negri bodiesNegri bodiesNegri bodies are eosinophilic, sharply outlined, pathognomonic inclusion bodies found in the cytoplasm of certain nerve cells containing the virus of rabies, especially in Ammon's horn of the hippocampus. Often also found in the cerebellar cortex of postmortem brain samples of rabies victims.They...
in RabiesRabiesRabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms... - Guarnieri bodies in Small pox
- Henderson-Peterson bodies in Molluscum contagiosumMolluscum contagiosumMolluscum contagiosum is a viral infection of the skin or occasionally of the mucous membranes. It is caused by a DNA poxvirus called the molluscum contagiosum virus . MCV has no animal reservoir, infecting only humans. There are four types of MCV, MCV-1 to -4; MCV-1 is the most prevalent and...
Intranuclear acidophilic-
- Cowdry type A in Herpes simplex virusHerpes simplex virusHerpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
and Varicella zoster virusVaricella zoster virusVaricella zoster virus is one of eight herpes viruses known to infect humans . It commonly causes chicken-pox in children and Herpes zoster in adults and rarely in children.-Nomenclature:...
and Torres bodies in Yellow feverYellow feverYellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family.... - Cowdry type B in Polio
Intranuclear basophilic-
- Cowdry type B in Adenovirus
- "owl eyes" in cytomegalovirusCytomegalovirusCytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...
Both intranuclear and intracytoplasmic-
- Warthin finkeldey bodies in MeaslesMeaslesMeasles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
Examples of viral inclusion bodies in plants http://plantpath.ifas.ufl.edu/pdc/Inclusionpage/Florvirus.html include aggregations of virus particles (like those for Cucumber mosaic virus http://plantpath.ifas.ufl.edu/pdc/Inclusionpage/CMV/CucMoInc.html) and aggregations of viral proteins (like the cylindrical inclusions of potyviruses http://plantpath.ifas.ufl.edu/pdc/Inclusionpage/Poty/poty.html). 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 http://plantpath.ifas.ufl.edu/pdc/Inclusionpage/Howto.html.
Inclusion bodies in Erythrocytes
Normally a red blood cellRed blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
does not contain inclusions in the cytoplasm. However, it may be seen because of certain hematologic disorders.
There are three kinds of erythrocyte inclusions:
- Developmental Organelles
- Howell-Jolly bodies: small, round fragments of the nucleus resulting from karyorrhexisKaryorrhexisKaryorrhexis is the destructive fragmentation of the nucleus of a dying cell whereby its chromatin is distributed irregularly throughout the cytoplasm. It is usually preceded by pyknosis and is followed by karyolysis and can occur as a result of either programmed cell death or necrosis....
or nuclear disintegration of the late reticulocyteReticulocyteReticulocytes are immature red blood cells, typically composing about 1% of the red cells in the human body.Reticulocytes develop and mature in the red bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells. Like mature red blood cells,...
and stain reddish-blue with Wright stain. - Basophilic stipplings - this stipplings is either fine or coarse, deep blue to purple staining inclusion that appears in erythrocytes on a dried Wright stain.
- Pappenheimer bodiesPappenheimer bodiesPappenheimer bodies are abnormal granules of iron found inside red blood cells on routine blood stain.They are a type of inclusion body formed by phagosomes that have engulfed excessive amounts of iron. They appear as dense, blue-purple granules within the red blood cell and there are usually only...
- are sideroticSiderosisSiderosis is the deposition of iron in tissue.When used without qualification, it usually refers to an environmental disease of the lung.Also Siderosis Bulbi, deposition of iron into the eye causing injury as the material chemically reacts with tissues and cells.-Causative agent:Iron oxide present...
granules which are small, irregular, dark-staining granules that appear near the periphery of a young erythrocyte in a Wright stain. - Polychromatophilic red cells - young red cells that no longer have nucleus but still contain some RNA.
- Cabot RingsCabot ringsCabot rings are thin, red-violet staining, threadlike strands in the shape of a loop or figure-8 that are found on rare occasions in erythrocytes...
- ring-like structure and may appear in erythrocytes in megaloblastic anemiaMegaloblastic anemiaMegaloblastic anemia is an anemia that results from inhibition of DNA synthesis in red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis stage...
or in severe anemias, lead poisoningLead poisoningLead poisoning is a medical condition caused by increased levels of the heavy metal lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and tissues including the heart, bones, intestines, kidneys, and reproductive and nervous systems...
, and in dyserythropoiesis, in which erythrocytes are destroyed before being released from the bone marrowBone marrowBone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
.
- Howell-Jolly bodies: small, round fragments of the nucleus resulting from karyorrhexis
- Abnormal Hemoglobin Precipitation
- Heinz bodies - round bodies, refractile inclusions not visible on a Wright stain film. It is best identified by supravital staining with basic dyes.
- HemoglobinHemoglobinHemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
H Inclusions - alpha thalassemiaThalassemiaThalassemia is an inherited autosomal recessive blood disease that originated in the Mediterranean region. In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin...
, 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.
- Protozoan Inclusion
- MalariaMalariaMalaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
- BabesiaBabesiaBabesia is a protozoan parasite of the blood that causes a hemolytic disease known as Babesiosis. There are over 100 species of Babesia identified; however only a handful have been documented as pathogenic in humans....
- Malaria