Viral regulators of complement activation: Structure, function and evolution

Ojha, Hina; Panwar, Hemendra Singh; Gorham, Ronald D.; Morikis, Dimitrios; Sahu, Arvind

doi:10.1016/j.molimm.2014.06.004

Cited by 25 publications

(27 citation statements)

References 102 publications

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“…Orthopox viruses have found a distinct approach for harvesting the regulatory power of RCA: rather than recruiting host regulators, they express RCA mimics. Despite being much smaller than FH, some of these mimics combine strong DAA and/or CA activities with surface‐binding capacity in just four domains . Examples include the smallpox inhibitor of complement enzymes (SPICE) and the vaccinia virus complement control protein (VCP); even though these proteins only differ in 11 aa, their complement‐inhibitory activity can vary by several orders of magnitude .…”

Section: A Force That Needs To Be Controlled: C3 As a Microbial Immunmentioning

confidence: 99%

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Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Ricklin

Reis

Mastellos

et al. 2016

Immunological Reviews

334

295

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Summary As a preformed defense system, complement faces a delicate challenge in providing an immediate, forceful response to pathogens even at first encounter, while sparing host cells in the process. For this purpose, it engages a tightly regulated network of plasma proteins, cell surface receptors, and regulators. Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses. In recent years, it has become evident that nature engages the power of C3 not only to clear pathogens but also for a variety of homeostatic processes ranging from tissue regeneration and synapse pruning to clearing debris and controlling tumor cell progression. At the same time, its central position in immune surveillance makes C3 a target for microbial immune evasion and, if improperly engaged, a trigger point for various clinical conditions. In our review, we look at the versatile roles and evolutionary journey of C3, discuss new insights into the molecular basis for C3 function, provide examples of disease involvement, and summarize the emerging potential of C3 as a therapeutic target.

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Section: A Force That Needs To Be Controlled: C3 As a Microbial Immunmentioning

confidence: 99%

“…Viral RCA mimics are not unique to poxviruses, though, and are also expressed by certain herpes viruses (e.g. KAPOSICA from the Kaposi's sarcoma‐associated herpesvirus) . In addition, some herpes viruses also utilize non‐RCA‐based complement inhibitors .…”

Section: A Force That Needs To Be Controlled: C3 As a Microbial Immunmentioning

confidence: 99%

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Ricklin

Reis

Mastellos

et al. 2016

Immunological Reviews

334

295

View full text Add to dashboard Cite

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“…For example, poxviruses control host complement by secreting CD46-like proteins that share 30–40% homology (73, 74). They consist of three to four CCPs that structurally and functionally mimic CD46 and CD55.…”

Section: Membrane Cofactor Protein Mutationsmentioning

confidence: 99%

Complement Dysregulation and Disease: Insights from Contemporary Genetics

Liszewski

Java

Schramm³

et al. 2017

Annu. Rev. Pathol. Mech. Dis.

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The vertebrate complement system consists of sequentially interacting proteins that provide for a rapid and powerful host defense. Nearly 60 proteins comprise three activation pathways (classical, alternative, and lectin) and a terminal cytolytic pathway common to all. Attesting to its potency, nearly half of the system’s components are engaged in its regulation. An emerging theme over the past decade is that variations in these inhibitors predispose to two scourges of modern humans. One, occurring most often in childhood, is a rare but deadly thrombomicroangiopathy called atypical hemolytic uremic syndrome. The other, age-related macular degeneration, is the most common form of blindness in the elderly. Their seemingly unrelated clinical presentations and pathologies share the common theme of overactivity of the complement system’s alternative pathway. This review summarizes insights gained from contemporary genetics for understanding how dysregulation of this powerful innate immune system leads to these human diseases.

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“…Poxviruses express CD46-like proteins (30–40 % homologous) to control host complement [31, 32]. Called poxviral inhibitors of complement enzymes (PICES), proteins from variola, and monkeypox are named SPICE (smallpox inhibitor of complement enzymes) and MOPICE (monkeypox inhibitor of complement enzymes), respectively [31–34].…”

Section: Introductionmentioning

confidence: 99%

Complement regulator CD46: genetic variants and disease associations

Liszewski

Atkinson

2015

Hum Genomics

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Membrane cofactor protein (MCP; CD46) is an ubiquitously expressed complement regulatory protein that protects host cells from injury by complement. This type-I membrane glycoprotein serves as a cofactor for the serine protease factor I to mediate inactivation of C3b and C4b deposited on host cells. More than 60 disease-associated mutations in MCP have now been identified. The majority of the mutations are linked to a rare thrombotic microangiopathic-based disease, atypical hemolytic uremic syndrome (aHUS), but new putative links to systemic lupus erythematosus, glomerulonephritis, and pregnancy-related disorders among others have also been identified. This review summarizes our current knowledge of disease-associated mutations in this complement inhibitor.

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Viral regulators of complement activation: Structure, function and evolution

Cited by 25 publications

References 102 publications

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Complement Dysregulation and Disease: Insights from Contemporary Genetics

Complement regulator CD46: genetic variants and disease associations

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