Double-stranded RNA viruses

Double-stranded waffle viruses
Electron micrograph of rotaviruses. The bar = 100 nm
Virus classification
Group: Group III (dsRNA)
Families
Birnaviridae Cystoviridae Hypoviridae Partitiviridae Reoviridae Totiviridae

Double-stranded (ds) RNA viruses are a diverse group of viruses that vary widely in host range (humans, animals, plants, fungi, and bacteria), genome segment number (one to twelve), and virion organization (T-number, capsid layers, or turrets). Members of this group include the rotaviruses, known globally as a common cause of gastroenteritis in young children, and bluetongue virus, an economically important pathogen of cattle and sheep.

Viruses with dsRNA genomes are currently grouped into six families: Reoviridae, Birnaviridae, Totiviridae, Partitiviridae, Hypoviridae, and Cystoviridae. Of these six families, the Reoviridae is the largest and most diverse in terms of host range.

In recent years virus particle assembly, virus-cell interactions, and viral pathogenesis, approaches for the development of novel antiviral strategies and/or agents can be designed.

Reoviridae

Reoviridae are currently classified into nine genera. The genomes of these viruses consist of 10 to 12 segments of dsRNA, each generally encoding one protein. The mature virions are non-enveloped. Their capsids, formed by multiple proteins, have icosahedral symmetry and are arranged generally in concentric layers. A distinguishing feature of the dsRNA viruses, irrespective of their family association, is their ability to carry out transcription of the dsRNA segments, under appropriate conditions, within the capsid. In all these viruses, the enzymes required for endogenous transcription are thus part of the virion structure.

Orthoreoviruses

The orthoreoviruses (reoviruses) are the prototypic members of the virus Reoviridae family and representative of the turreted members, which comprise about half the genera. Like other members of the family, the reoviruses are non-enveloped and characterized by concentric capsid shells that encapsidate a segmented dsRNA genome. In particular, reovirus has eight structural proteins and ten segments of dsRNA. A series of uncoating steps and conformational changes accompany cell entry and replication. High-resolution structures are known for almost all of the proteins of mammalian reovirus (MRV), which is the best-studied genotype. Electron cryo-microscopy (cryoEM) and X-ray crystallography have provided a wealth of structural information about two specific MRV strains, type 1 Lang (T1L) and type 3 Dearing (T3D).

Cypovirus

The cytoplasmic polyhedrosis viruses (CPVs) form the genus Cypovirus of the family Reoviridae. CPVs are classified into 14 species based on the electrophoretic migration profiles of their genome segments. Cypovirus has only a single capsid shell, which is similar to the orthoreovirus inner core. CPV exhibits striking capsid stability and is fully capable of endogenous RNA transcription and processing. The overall folds of CPV proteins are similar to those of other reoviruses. However, CPV proteins have insertional domains and unique structures that contribute to their extensive intermolecular interactions. The CPV turret protein contains two methylase domains with a highly conserved helix-pair/β-sheet/helix-pair sandwich fold but lacks the β-barrel flap present in orthoreovirus λ2. The stacking of turret protein functional domains and the presence of constrictions and A spikes along the mRNA release pathway indicate a mechanism that uses pores and channels to regulate the highly coordinated steps of RNA transcription, processing, and release.

Rotaviruse

Rotavirus is the most common cause of acute gastroenteritis in infants and young children worldwide. This virus contains a dsRNA genome and is a member of the Reoviridae family. The genome of rotavirus consists of eleven segments of dsRNA. Each genome segment codes for one protein with the exception of segment 11, which codes for two proteins. Among the twelve proteins, six are structural and six are non-structural proteins.

Bluetongue virus

The members of Orbivirus genus within the Reoviridae family are arthropod-borne viruses and are responsible for high morbidity and mortality in ruminants. Bluetongue virus (BTV) which causes disease in livestock (sheep, goat, cattle) has been in the forefront of molecular studies for the last three decades and now represents the best understood orbivirus at the molecular and structural levels. BTV, like other members of the family, is a complex non-enveloped virus with seven structural proteins and a RNA genome consisting of 10 variously sized dsRNA segments.

Phytoreoviruses

Phytoreoviruses are non-turreted reoviruses that are major agricultural pathogens, particularly in Asia. One member of this family, Rice Dwarf Virus (RDV), has been extensively studied by electron cryomicroscopy and x-ray crystallography. From these analyses, atomic models of the capsid proteins and a plausible model for capsid assembly have been derived. While the structural proteins of RDV share no sequence similarity to other proteins, their folds and the overall capsid structure are similar to those of other Reoviridae.

L-A Virus

The L-A dsRNA virus of the yeast Saccharomyces cerevisiae has a single 4.6 kb genomic segment that encodes its major coat protein, Gag (76 kDa) and a Gag-Pol fusion protein (180 kDa) formed by a -1 ribosomal frameshift. L-A can support the replication and encapsidation in separate viral particles of any of several satellite dsRNAs, called M dsRNAs, each of which encodes a secreted protein toxin (the killer toxin) and immunity to that toxin. L-A and M are transmitted from cell to cell by the cytoplasmic mixing that occurs in the process of mating. Neither is naturally released from the cell or enters cells by other mechanisms, but the high frequency of yeast mating in nature results in the wide distribution of these viruses in natural isolates. Moreover, the structural and functional similarities with dsRNA viruses of mammals has made it useful to consider these entities as viruses.

Infectious bursal disease virus

Infectious bursal disease virus (IBDV) is the best-characterized member of the family Birnaviridae. These viruses have bipartite dsRNA genomes enclosed in single-layered icosahedral capsids with T = 13l geometry. IBDV shares functional strategies and structural features with many other icosahedral dsRNA viruses, except that it lacks the T = 1 (or pseudo T = 2) core common to the Reoviridae, Cystoviridae, and Totiviridae. The IBDV capsid protein exhibits structural domains that show homology to those of the capsid proteins of some positive-sense single-stranded RNA viruses, such as the nodaviruses and tetraviruses, as well as the T = 13 capsid shell protein of the Reoviridae. The T = 13 shell of the IBDV capsid is formed by trimers of VP2, a protein generated by removal of the C-terminal domain from its precursor, pVP2. The trimming of pVP2 is performed on immature particles as part of the maturation process. The other major structural protein, VP3, is a multifunctional component lying under the T = 13 shell that influences the inherent structural polymorphism of pVP2. The virus-encoded RNA-dependent RNA polymerase, VP1, is incorporated into the capsid through its association with VP3. VP3 also interacts extensively with the viral dsRNA genome.

Bacteriophage Φ6

Bacteriophage Φ6, is a member of the Cystoviridae family. It infects Pseudomonas bacteria (typically plant-pathogenic P. syringae). It has a three-part, segmented, double-stranded RNA genome, totalling ~13.5 kb in length. Φ6 and its relatives have a lipid membrane around their nucleocapsid, a rare trait among bacteriophages. It is a lytic phage, though under certain circumstances has been observed to display a delay in lysis which may be described as a "carrier state".

RNA virus

An RNA virus is a virus that has RNA (ribonucleic acid) as its genetic material. This nucleic acid is usually single-stranded RNA (ssRNA) but may be double-stranded RNA (dsRNA). The ICTV classifies RNA viruses as those that belong to Group III, Group IV or Group V of the Baltimore classification system of classifying viruses, and does not consider viruses with DNA intermediates as RNA viruses. Notable human diseases caused by RNA viruses include SARS, influenza and hepatitis C.

Another term for RNA viruses that explicitly excludes retroviruses is ribovirus.

Characteristics

Single-stranded RNA viruses and RNA Sense

RNA viruses can be further classified according to the sense or polarity o

f their RNA into negative-sense and positive-sense, or ambisense RNA viruses. Positive-sense viral RNA is identical to viral mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation. As such, purified RNA of a positive-sense virus can directly cause infection though it may be less infectious than the whole virus particle. Purified RNA of a negative-sense virus is not infectious by itself as it needs to be transcribed into positive-sense RNA. Ambisense RNA viruses resemble negative-sense RNA viruses, except they also translate genes from the positive strand.

Double-stranded RNA viruses

The double-stranded (ds)RNA viruses represent a diverse group of viruses that vary widely in host range (humans, animals, plants, fungi, and bacteria), genome segment number (one to twelve), and virion organization (T-number, capsid layers, or turrets). Members of this group include the rotaviruses, renowned globally as the commonest cause of gastroenteritis in young children, and bluetongue virus, an economically important pathogen of cattle and sheep. In recent years, remarkable progress has been made in determining, at atomic and subnanometeric levels, the structures of a number of key viral proteins and of the virion capsids of several dsRNA viruses, highlighting the significant parallels in the structure and replicative processes of many of these viruses.

Mutation rates

RNA viruses generally have very high mutation rates as they lack DNA polymerases which can find and fix mistakes, and are therefore unable to conduct DNA repair of damaged genetic material. DNA viruses have considerably lower mutation rates due to the proof-reading ability of DNA polymerases within the host cell. Retroviruses have a high mutation rate even though their DNA intermediate integrates into the host genome (and is thus subject to host DNA proofreading once integrated), because errors during reverse transcription are embedded into both strands of DNA prior to integration.

Although RNA usually mutates rapidly, recent work found that the SARS virus and related RNA viruses contain a gene that mutates very slowly. The gene in question has a complex three-dimensional structure which is hypothesized to provide a chemical function necessary for viral propagation, perhaps as a ribozyme. If so, most mutations would render it unfit for that purpose and would not propagate.

Replication

Animal RNA viruses are classified into three distinct groups depending on their genome and mode of replication (and the numerical groups based on the older Baltimore classification):

• Double-stranded RNA viruses (Group III) contain from one to a dozen different RNA molecules, each of which codes for one or more viral proteins.
• Positive-sense ssRNA viruses (Group IV) have their genome directly utilized as if it were mRNA, producing a single protein which is modified by host and viral proteins to form the various proteins needed for replication. One of these includes RNA-d ependent RNA polymerase, which copies the viral RNA to form a double-stranded replicative form, in turn this directs the formation of new virions.
• Negative-sense ssRNA viruses (Group V) must have their genome copied by an RNA polymerase to form positive-sense RNA. This means that the virus must bring along with it the RNA-dependent RNA polymerase enzyme. The positive-sense RNA molecule then acts as viral mRNA, which is translated into proteins by the host ribosomes. The resultant protein goes on to direct the synthesis of new virions, such as capsid proteins and RNA replicase, which is used to produce new negative-sense RNA molecules.

  

Retroviruses (Group VI) have a single-stranded RNA genome but are generally not considered RNA viruses because they use DNA intermediates to replicate. Reverse transcriptase, a viral enzyme that comes from the virus itself after it is uncoated, converts the viral RNA into a complementary strand of DNA, which is copied to produce a double stranded molecule of viral DNA. After this DNA is integrated, expression of the encoded genes may lead the formation of new virions.

Group III - dsRNA viruses

• Family Birnaviridae
• Family Chrysoviridae
• Family Cystoviridae
• Family Hypoviridae
• Family Partitiviridae
• Family Reoviridae - includes Rotavirus
• Family Totiviridae
• Unassigned genera
  • 
    
  Endornavirus

Group IV - positive-sense ssRNA viruses

• Order Nidovirales
  • Family Arteriviridae
  • Family Coronaviridae - includes Coronavirus, SARS
  • Family Roniviridae
• Unassigned
  • Family Astroviridae
  • Family Barnaviridae
  • Family Bromoviridae
  • Family Caliciviridae - includes Norwalk virus
  • Family Closteroviridae
  • Family Comoviridae
  • Family Dicistroviridae
  • Family Flaviviridae - includes Yellow fever virus, West Nile virus, Hepatitis C virus, Dengue fever virus
  • Family Flexiviridae
  • Family Leviviridae
  • Family Luteoviridae - includes Barley yellow dwarf virus
  • Family Marnaviridae
  • Family Narnaviridae
  • Family Nodaviridae
  • Family Picornaviridae - includes Poliovirus, the common cold virus, Hepatitis A virus
  • Family Potyviridae
  • Family Sequiviridae
  • Family Tetraviridae
  • Family Togaviridae - includes Rubella virus, Ross River virus, Sindbis virus,Chikungunya virus
  • Family Tombusviridae
  • Family Tymoviridae
  • Unassigned genera
    • Genus Benyvirus
    • Genus Cheravirus
    • Genus Furovirus
    • Genus Hepevirus - includes Hepatitis E virus
    • Genus Hordeivirus
    • Genus Idaeovirus
    • Genus Ourmiavirus
    • Genus Pecluvirus
    • Genus Pomovirus
    • Genus Sadwavirus
    • Genus Sobemovirus
    • Genus Tobamovirus - includes tobacco mosaic virus
    • Genus Tobravirus
    • Genus Umbravirus

Group V - negative-sense ssRNA viruses

• Order Mononegavirales
  • Family Bornaviridae - Borna disease virus
  • Family Filoviridae - includes Ebola virus, Marburg virus
  • Family Paramyxoviridae - includes Measles virus, Mumps virus, Nipah virus, Hendra virus
  • Family Rhabdoviridae - includes Rabies virus
• Unassigned
  • Family Arenaviridae - includes Lassa virus
  • Family Bunyaviridae - includes Hantavirus
  • Family Orthomyxoviridae - includes Influenza viruses
  • Unassigned genera:
    • Genus Deltavirus
    • Genus Ophiovirus
    • Genus Tenuivirus
    • Genus Varicosavirus

Antisense RNA

Antisense RNA is single-stranded RNA that is complementary to a messenger RNA (mRNA) strand transcribed within a cell. Antisense RNA may be introduced into a cell to inhibit translation of a complementary mRNA by base pairing to it and physically obstructing the translation machinery. This effect is therefore stoichiometric. An example of naturally occurring mRNA antisense mechanism is the hok/sok system of the E.coli R1 plasmid. Antisense RNA has long been thought of as a promising technique for disease therapy; the only such case to have reached the market is the drug fomivirsen. One commentator has characterized antisense RNA as one of "dozens of technologies that are gorgeous in concept, but exasperating in [commercialization]". Generally, antisense RNA still lack effective design, biological activity, and efficient route of administration.

Historically, the effects of antisense RNA have often been confused with the effects of RNA interference, a related process in which double-stranded RNA fragments called small interfering RNAs trigger catalytically mediated gene silencing, most typically by targeting the RNA-induced silencing complex (RISC) to bind to and degrade the mRNA. Attempts to genetically engineer transgenic plants to express antisense RNA instead activate the RNAi pathway, although the processes result in differing magnitudes of the same downstream effect, gene silencing. Well-known examples include the Flavr Savr tomato and two cultivars of ringspot-resistant papaya.

Transcription of longer cis-antisense transcripts is a common phenomenon in the mammalian transcriptome. Although the function of some cases have been described, such as the Zeb2/Sip1 antisense RNA, no general function has been elucidated. In the case of Zeb2/Sip1, the antisense noncoding RNA is opposite the 5' splice site of an intron in the 5'UTR of the Zeb2 mRNA. Expression of the antisense ncRNA prevents splicing of an intron that contains a ribosome entry site necessary for efficient expression of the Zeb2 protein. Transcription of long antisense ncRNAs is often concordant with the associated protein-coding gene, but more detailed studies have revealed that the relative expression patterns of the mRNA and antisense ncRNA are complex.

Sense (molecular biology)

Sense, when applied in a molecular biology context, is a general concept used to compare the polarity of nucleic acid molecules, such as DNA or RNA, to other nucleic acid molecules. Depending on the context within molecular biology, sense may have slightly different meanings.

DNA sense

Molecular biologists call a DNA single strand or sequence sense (or positive sense) if an RNA version of the same sequence is translated or translatable into protein, and they call its complement antisense (or negative sense). Sometimes the phrase coding strand is encountered; however, protein coding and non-coding RNA's can be transcribed similarly from both strands, in some cases being transcribed in both directions from a common promoter region, or being transcribed from within introns, on both strands.

Antisense DNA

Schematic showing how antisense DNA strands can interfere with protein translation.

Antisense molecules interact with complementary strands of nucleic acids, modifying expression of genes.

Some regions within a double strand of DNA code for genes, which are usually instructions specifying the order of amino acids in a protein along with regulatory sequences, splicing sites, noncoding introns and other complicating details. For a cell to use this information, one strand of the DNA serves as a template for the synthesis of a complementary strand of RNA. The template DNA strand is called the transcribed strand with antisense sequence and the mRNA transcript is said to be sense sequence (the complement of antisense). Because the DNA is double-stranded, the strand complementary to the antisense sequence is called non-transcribed strand and has the same sense sequence as the mRNA transcript (though T bases in DNA are substituted with U bases in RNA).

DNA strand 1: sense strand

DNA strand 2: antisense strand (copied to)→ RNA strand (sense)

Many forms of antisense have been developed and can be broadly categorized into enzyme-dependent antisense or steric blocking antisense.

Enzyme-dependent antisense includes forms dependent on RNase H activity to degrade target mRNA, including single-stranded DNA, RNA, and phosphorothioate antisense. The R1 plasmid hok/sok system is an example of mRNA antisense regulation process, through enzymatic degradation of the resulting RNA duplex. Double stranded RNA acts as enzyme-dependent antisense through the RNAi/siRNA pathway, involving target mRNA recognition through sense-antisense strand pairing followed by target mRNA degradation by the RNA-induced silencing complex (RISC).

Steric blocking antisense (RNase-H independent antisense) interferes with gene expression or other mRNA-dependent cellular processes by binding to a target sequence of mRNA and getting in the way of other processes. Steric blocking antisense includes 2'-O alkyl (usually in chimeras with RNase-H dependent antisense), peptide nucleic acid (PNA), locked nucleic acid (LNA) and Morpholino antisense.

Antisense nucleic acid molecules have been used experimentally to bind to mRNA and prevent expression of specific genes. Antisense therapies are also in development; in the USA, the Food and Drug Administration (FDA) has approved a phosphorothioate antisense oligo, fomivirsen (Vitravene), for human therapeutic use.

Cells can produce antisense RNA molecules naturally, which interact with complementary mRNA molecules and inhibit their expression.

Ambisense

A single-stranded genome which contains both positive-sense and negative-sense is said to be ambisense. Bunya viruses have 3 single-stranded RNA (ssRNA) fragments containing both positive-sense and negative-sense sections; arenaviruses are also ssRNA viruses with an ambisense genome, as they have 2 fragments which are mainly negative-sense except for part of the 5' ends of the large and small segments of their genome.

Antisense mRNA

Antisense mRNA is an mRNA transcript that is complementary to endogenous mRNA. In other words, it is a non-coding strand complementary to the coding sequence of mRNA; this is similar to negative-sense viral RNA. Introducing a transgene coding for antisense mRNA is a technique used to block expression of a gene of interest. Radioactively-labelled antisense mRNA can be used to show the level of transcription of genes in various cell types. Some alternative antisense structural types are being experimentally applied as antisense therapy, with at least one antisense therapy approved for use in humans.

RNA sense

In virology, the genome of a RNA virus can be said to be either positive-sense, also known as a "plus-strand", or negative-sense, also known as a "minus-strand". In most cases, the terms sense and strand are used interchangeably, making such terms as positive-strand equivalent to positive-sense, and plus-strand equivalent to plus-sense. Whether a virus is positive-sense or negative-sense can be used as a basis for classifiying viruses.

Positive-sense

Positive-sense (5' to 3') viral RNA signifies that a particular viral RNA sequence may be directly translated into the desired viral proteins. Therefore, in positive-sense RNA viruses, the viral RNA genome can be considered viral mRNA, and can be immediately translated by the host cell. Unlike negative-sense RNA, positive-sense RNA is of the same sense as mRNA. Some viruses (e.g. Coronaviridae) have positive-sense genomes which can act as mRNA and be used directly to synthesise proteins without the help of a complementary RNA intermediate. Because of this, these viruses do not need to have an RNA transcriptase packaged into the virion.

Negative-sense

Negative-sense (3' to 5') viral RNA is complementary to the viral mRNA and thus must be converted to positive-sense RNA by an RNA polymerase prior to translation. Negative-sense RNA (like DNA) has a nucleotide sequence complementary to the mRNA that it encodes. Like DNA, this RNA cannot be translated into protein directly. Instead, it must first be transcribed into a positive-sense RNA which acts as an mRNA. Some viruses (Influenza, for example) have negative-sense genomes and so must carry an RNA polymerase inside the virion.

Magnetic immunoassay

Magnetic immunoassay (MIA) is a novel type of diagnostic immunoassay utilizing magnetic beads as labels in lieu of conventional enzymes (ELISA), radioisotopes (RIA) or fluorescent moieties (fluorescent immunoassays). This assay involves the specific binding of an antibody to its antigen, where a magnetic label is conjugated to one element of the pair. The presence of magnetic beads is then detected by a magnetic reader (magnetometer) which measures the magnetic field change induced by the beads. The signal measured by the magnetometer is proportional to the analyte (virus, toxin, bacteria, cardiac marker,etc.) quantity in the initial sample.

Magnetic labels

Magnetic beads are comprised of nanometric-sized iron oxide particles encapsulated or glued together with polymers. These magnetic beads range from 35nm up to 4.5μm. The component magnetic nanoparticles range from 5 to 50nm and exhibit a unique quality referred to as superparamagnetism in the presence of an externally applied magnetic field. First discovered by Frenchman Louis Néel, Nobel Physics Prize winner in 1970, this superparamagnetic quality has already been utilized for medical application in Magnetic Resonance Imaging (MRI) and in biological separations, but not yet for labeling in commercial diagnostic applications. Magnetic labels exhibit several features very well adapted for such applications:

• they are not affected by reagent chemistry or photo-bleaching and are therefore stable over time,
• the magnetic background in a biomolecular sample is usually insignificant,
• sample turbidity or staining have no impact on magnetic properties,
• magnetic beads can be manipulated remotely by magnetism.

Magnetometers

A simple instrument can detect the presence and measure the total magnetic signal of a sample, however the challenge of developing an effective MIA is to separate naturally occurring magnetic background (noise) from the weak magnetically labeled target (signal). Various approaches and devices have been employed to achieve a meaningful signal-to-noise ratio (SNR) for bio-sensing applications: giant magneto-resistive sensors and spin valves, piezo-resistive cantilevers, inductive sensors, superconducting quantum interference devices, anisotropic magneto-resistive rings, and miniature Hall sensors. But improving SNR often requires a complex instrument to provide repeated scanning and extrapolation through data processing, or precise alignment of target and sensor of miniature and matching size. Beyond this requirement, MIA that exploits the non-linear magnetic properties of magnetic labels can effectively utilize the intrinsic ability of a magnetic field to pass through plastic, water, nitrocellulose, and other materials, thus allowing for true volumetric measurements in various immunoassay formats. Unlike conventional methods that measure the susceptibility of superparamagnetic materials, a MIA based on non-linear magnetization eliminates the impact of linear dia- or paramagnetic materials such as sample matrix, consumable plastics and/or nitrocellulose. Although the intrinsic magnetism of these materials is very weak, with typical susceptibility values of –10^-5 (dia) or +10^-3 (para), when one is investigating very small quantities of superparamagnetic materials, such as nanograms per test, the background signal generated by ancillary materials cannot be ignored. In MIA based on non-linear magnetic properties of magnetic labels the beads are exposed to an alternating magnetic field at two frequencies, f1 and f2. In the presence of non-linear materials such as superparamagnetic labels, a signal can be recorded at combinatorial frequencies, for example, at f = f1 ± 2×f2. This signal is exactly proportional to the amount of magnetic material inside the reading coil.

This technology,makes magnetic immunoassay possible in a variety of formats such as:

• conventional lateral flow test by replacing gold labels with magnetic labels,
• vertical flow tests allowing for the interrogation of rare analytes (such as bacteria) in large-volume samples
• microfluidic applications and biochip

It was also described for in vivo applications and for multiparametric testing.

Secondary antibody

The primary antibody (in purple) binds to an antigen (in red). A labeled secondary antibody (in green), then binds to the primary antibody. The label is then used to indirectly detect the antigen.

A secondary antibody is an antibody that binds to primary antibodies or antibody fragments. They are typically labeled with probes that make them useful for detection, purification or cell sorting applications.

Secondary antibodies may be polyclonal or monoclonal, and are available with specificity for whole Ig molecules or antibody fragments such as the Fc or Fab regions.

Specific secondary antibodies are usually chosen to work in specific laboratory applications. Frequently, any one of several secondary antibodies perform adequately in a particular application. They are selected according to the source of the primary antibody, the class of the primary antibody (e.g., IgG or IgM), and the kind of label which is preferred. Identifying the optimal secondary antibody is normally done through trial and error.

Applications

Secondary antibodies are used in many biochemical assays including:

• ELISA, including many HIV tests
• Western blot
  
• Immunostaining
• Immunohistochemistry
• Immunocytochemistry

Nomenclature of monoclonal antibodies

Complete list of stems for
monoclonal antibody nomenclature

Prefix	Target		Source		Suffix
variable	-vi(r)-	viral	-u-	human	-mab
	-ba(c)-	bacterial	-o-	mouse
	-li(m)-	immune system	-a-	rat
	-le(s)-	infectious lesions	-e-	hamster
	-ci(r)-	cardiovascular	-i-	primate
	-fu(ng)-	fungal	-xi-	chimeric
	-ne(r)-	nervous system	-zu-	humanized
	-ki(n)-	interleukin as target	-axo-	rat/murine hybrid
	-mu(l)-	musculoskeletal	-xizu-	chimeric + humanized
	-o(s)-	bone
	-tox(a)-	toxin as target
	-anib(i)-	angiogenesis
	-co(l)-	colonic tumor
	-me(l)-	melanoma
	-ma(r)-	mammary tumor
	-go(t)-	testicular tumor
	-go(v)-	ovarian tumor
	-pr(o)-	prostate tumor
	-tu(m)-	miscellaneous tumor

The nomenclature of monoclonal antibodies is a naming scheme for assigning generic, or nonproprietary, names to a group of medicines called monoclonal antibodies. This scheme is used for both the World Health Organization’s International Nonproprietary Names and the United States Adopted Names. In general, suffixes are used to identify a class of medicines; all monoclonal antibody pharmaceuticals end with the suffix -mab. However, different infixes are used depending on the structure and function of the medicine.

Components

Infix for origin/source

The infix preceding the -mab suffix denotes the animal origin of the antibodies. Although the original monoclonal antibodies were produced in mice (infix, -o-), these antibodies are recognized as foreign by human immune systems and may be rapidly cleared, provoke an allergic reaction, or both. Therefore, parts of the antibody may be replaced with human sequences. If the constant region is replaced with the human form, it is termed chimeric and the infix used is -xi-. Part of the variable regions may also be substituted, in which case it is termed humanized and the infix used is -zu-. Antibodies originating in humans use -u-.

Infix for target

The infix preceding the source of the antibodies refers to medicine’s target. Most of these consist of a consonant, vowel, then another consonant. For ease of pronunciation and to avoid awkwardness, the final consonant is dropped if the following infix begins with a consonant (such as -zu- or -xi-). Examples of these include -ci(r)- for the circulatory system and -tu(m)- for miscellaneous tumors (cancers).

Prefix and second word

Finally, the prefix carries no special meaning and should be unique for each medicine. A second word may be added if there is another substance attached or linked.

Examples

Abciximab is a commonly used medication to prevent platelets from clumping together. It can be broken down into ab- + -ci(r)- + -xi- + -mab. Therefore, it is a chimeric monoclonal antibody used on the cardiovascular system.

Another example is the breast cancer medication trastuzumab, which can be broken down into tras- + -tu(m)- + -zu- + -mab. Therefore, it is a humanized monoclonal antibody used against a tumor.