Virokines are

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s encoded by some large DNA

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

es that are

secrete 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...

d by the host cell and serve to evade the host's

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

. Such proteins are referred to as virokines if they resemble

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...

s, or complement regulators; the term viroceptor is sometimes used if the proteins resemble cellular receptors. A third class of virally encoded immunomodulatory proteins consists of proteins that bind directly to cytokines. Due to the immunomodulatory properties of these proteins, they have been proposed as potentially therapeutically relevant to

autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...

diseases.

Mechanism

The primary mechanism of virokine interference with immune signaling is thought to be

competitive inhibition Competitive inhibition is interruption of a chemical pathway owing to one chemical substance inhibiting the effect of another by competing with it for binding or bonding. Any metabolic or chemical messenger system can potentially be affected b ...

of the binding of host signaling molecules to their target receptors. Virokines occupy binding sites on host receptors, thereby inhibiting access by signaling molecules. Viroceptors mimic host receptors and thus divert signaling molecules from finding their targets. Cytokine-binding proteins bind to and sequester cytokines, occluding the binding surface through which they interact with receptors. The effect is to attenuate and subvert host immune response.

Discovery

The term "virokine" was coined by

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

virologist Virology is the scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host cells for reproduction, their ...

Bernard Moss Bernard Moss (born July 26, 1937 in Brooklyn) is a virologist at the National Institute of Allergy and Infectious Diseases, part of the United States National Institutes of Health. He is the Chief of the NIAID Laboratory of Viral Diseases and of ...

. The early 1990s saw several reports of virally encoded proteins with

sequence homology Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spe ...

to immune proteins, followed by reports of the

cowpox Cowpox is an infectious disease caused by the ''cowpox virus'' (CPXV). It presents with large blisters in the skin, a fever and swollen glands, historically typically following contact with an infected cow, though in the last several decades more ...

and

vaccinia ''Vaccinia virus'' (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the ...

viruses directly interfering with key immune regulator

IL1B Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin" ...

. The first identified virokine was an

epidermal growth factor Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-k Da and has 53 amino acid residues and three intramolecular disulfide bonds. EGF was originally descr ...

-like protein found in

myxoma virus ''Myxoma virus'' is a poxvirus in the genus ''Leporipoxvirus''. The two broad geographic types of ''myxoma virus'' are Californian and South American. Californian ''myxoma virus'' is found on the West Coast of the United States, the Baja Penins ...

es. Much of the early work on virokines involved

virus, which was discovered to secrete proteins that promote proliferation of neighboring cells and block

complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class ...

immune activity leading to

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

Evolutionary origins

The immunomodulatory proteins, including virokines, in the

poxvirus ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. There are currently 83 species in this family, divided among 22 genera, which are divided into two subfamilies. Diseases associated wit ...

family have been extensively studied in the context of the evolution of the family. Virokines in this family are thought to have been acquired from host genes and from other viruses through

horizontal gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between Unicellular organism, unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offsprin ...

. Similar observations have been made in the

herpesvirus ''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπειν ...

family; for example, Epstein-Barr virus encodes an

interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...

protein with high

sequence identity In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Ali ...

to the human

interleukin-10 Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti- inflammatory cytokine. In humans, interleukin 10 is encoded by the ''IL10'' gene. IL-10 signals through a receptor complex consisting of two IL-10 ...

, suggesting a recent evolutionary origin.

References

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External links

Cytokines & Cells Online Pathfinder Encyclopaedia
Molecular biology Virology