Virokines are proteins encoded by some large DNA viruses that are secreted by the host cell and serve to evade the host's immune system. Such proteins are referred to as virokines if they resemble cytokines, growth factors, or complement regulators; the term viroceptor is sometimes used if the proteins resemble cellular receptors.[1] A third class of virally encoded immunomodulatory proteins consists of proteins that bind directly to cytokines.[2] Due to the immunomodulatory properties of these proteins, they have been proposed as potentially therapeutically relevant to autoimmune diseases.[3]

Mechanism

The primary mechanism of virokine interference with immune signaling is thought to be competitive inhibition 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.[1][2]

Discovery

The term "virokine" was coined by National Institutes of Health virologist Bernard Moss.[4][5] The early 1990s saw several reports of virally encoded proteins with sequence homology to immune proteins, followed by reports of the cowpox and vaccinia viruses directly interfering with key immune regulator IL1B. The first identified virokine was an epidermal growth factor-like protein found in myxoma viruses.[6]

Much of the early work on virokines involved vaccinia virus, which was discovered to secrete proteins that promote proliferation of neighboring cells and block complement immune activity leading to inflammation.[5]

Evolutionary origins

The immunomodulatory proteins, including virokines, in the poxvirus 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.[7] Similar observations have been made in the herpesvirus family; for example, Epstein-Barr virus encodes an interleukin protein with high sequence identity to the human interleukin-10, suggesting a recent evolutionary origin.[3][8]

References

  1. 1 2 McFadden, Grant (June 2000). "Virus "Star Wars"". Science & Medicine (7): 38.
  2. 1 2 Alcami, A (January 2003). "Viral mimicry of cytokines, chemokines and their receptors". Nature Reviews. Immunology. 3 (1): 36–50. doi:10.1038/nri980. PMID 12511874. S2CID 23531422.
  3. 1 2 Lucas, A; McFadden, G (15 October 2004). "Secreted immunomodulatory viral proteins as novel biotherapeutics". Journal of Immunology. 173 (8): 4765–74. doi:10.4049/jimmunol.173.8.4765. PMID 15470015.
  4. ↑ "Dr. Bernard Moss Wins Bristol-Myers Squibb Award". National Institute of Allergy and Infectious Diseases. National Institutes of Health. 16 November 2000. Archived from the original on 20 December 2013. Retrieved 24 March 2015.
  5. 1 2 Kotwal, GJ; Moss, B (8 September 1988). "Vaccinia virus encodes a secretory polypeptide structurally related to complement control proteins". Nature. 335 (6186): 176–8. Bibcode:1988Natur.335..176K. doi:10.1038/335176a0. PMID 3412473. S2CID 7963129.
  6. ↑ Henderson, edited by Gerry A. Higgs, Brian (2000). Novel cytokine inhibitors. Basel: Birkhäuser Verlag. pp. 245–7. ISBN 9783764359423. {{cite book}}: |first1= has generic name (help)CS1 maint: multiple names: authors list (link)
  7. ↑ Odom, MR; Hendrickson, RC; Lefkowitz, EJ (September 2009). "Poxvirus protein evolution: family wide assessment of possible horizontal gene transfer events". Virus Research. 144 (1–2): 233–49. doi:10.1016/j.virusres.2009.05.006. PMC 2779260. PMID 19464330.
  8. ↑ Fickenscher, H; Hör, S; Küpers, H; Knappe, A; Wittmann, S; Sticht, H (February 2002). "The interleukin-10 family of cytokines". Trends in Immunology. 23 (2): 89–96. doi:10.1016/s1471-4906(01)02149-4. PMID 11929132.
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