Human astrovirus coat protein binds C1q and MBL and inhibits the classical and lectin pathways of complement activation

Hair, Pamela S.; Gronemus, Jenny Q.; Crawford, Katrina B.; Salvi, Veena P.; Cunnion, Kenji M.; Thielens, Nicole M.; Arlaud, Gérard J.; Rawal, Nenoo; Krishna, Neel K.

doi:10.1016/j.molimm.2009.10.006

Cited by 57 publications

(77 citation statements)

References 22 publications

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“…In conclusion, consistent with findings from other viral infections (4,6,8,10,12,(24)(25)(26), MBL2 polymorphisms known to lead to MBL deficiencies were associated with higher TTV VLs than was wild-type MBL2, supporting the view that innate immunity efficiency contributes to determining the TTV VL size. The increase was modest but might have been greater had we examined subjects earlier in infancy, when the role of MBL in antimicrobial resistance is most important (5,28).…”

supporting

confidence: 88%

“…MBL, encoded by gene MBL2 on chromosome 10, is a pattern recognition protein that exerts its protective action by activating the complement cascade through an antibody-independent pathway triggered by its binding to pathogen surfaces and other mechanisms (13). MBL is probably most important in antibacterial defenses (14) but also plays a significant role against viruses; indeed, MBL2 polymorphisms known to lead to lower-than-normal blood concentrations of functional MBL have been linked with an increased susceptibility to several enveloped and nonenveloped viruses (3,4,6,8,10,12,24,25,26). Furthermore, because the airways are colonized by TTV early in life and may represent a port of body entry (18), we conducted the investigation with patients being evaluated to confirm or exclude the presence of primary ciliary dyskinesia (PCD).…”

mentioning

confidence: 99%

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Torque Teno Virus Viremia Load Size in Patients with Selected Congenital Defects of Innate Immunity

Maggi

Pifferi

Michelucci³

et al. 2011

Clin. Vaccine Immunol.

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supporting

confidence: 88%

mentioning

confidence: 99%

Torque Teno Virus Viremia Load Size in Patients with Selected Congenital Defects of Innate Immunity

Maggi

Pifferi

Michelucci³

et al. 2011

Clin. Vaccine Immunol.

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“…Similarly to what has been observed with the IFN response, many pathogens have developed ingenious methods by which to evade destruction by the complement system (138). Purified recombinant HAstV capsid protein is able to inhibit complement-mediated hemolysis through direct interaction with two of the complement regulatory molecules, C1 and MBL (133,134). Both the classical and lectin activation pathways of complement may be inhibited by HAstV capsid protein.…”

Section: Host Immune Responses and Control Of Infectionmentioning

confidence: 91%

“…Indeed, evidence in this regard comes from published in vitro data on human viruses (132)(133)(134)(135)(136), as well as from in vivo studies with infected young turkeys (122,137) and immunodeficient mice (100). Unpublished studies in our laboratory have also explored the interplay between HAstV replication and the interferon (IFN) response in cultured cells, observing that infection of CaCo-2 cells induces little type I IFN (IFN-I) response and that this occurs at late stages of infection.…”

Section: Host Immune Responses and Control Of Infectionmentioning

confidence: 99%

Human Astroviruses

2014

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SUMMARY Human astroviruses (HAtVs) are positive-sense single-stranded RNA viruses that were discovered in 1975. Astroviruses infecting other species, particularly mammalian and avian, were identified and classified into the genera Mamastrovirus and Avastrovirus . Through next-generation sequencing, many new astroviruses infecting different species, including humans, have been described, and the Astroviridae family shows a high diversity and zoonotic potential. Three divergent groups of HAstVs are recognized: the classic ( MAstV 1 ), HAstV-MLB ( MAstV 6 ), and HAstV-VA/HMO ( MAstV 8 and MAstV 9 ) groups. Classic HAstVs contain 8 serotypes and account for 2 to 9% of all acute nonbacterial gastroenteritis in children worldwide. Infections are usually self-limiting but can also spread systemically and cause severe infections in immunocompromised patients. The other groups have also been identified in children with gastroenteritis, but extraintestinal pathologies have been suggested for them as well. Classic HAstVs may be grown in cells, allowing the study of their cell cycle, which is similar to that of caliciviruses. The continuous emergence of new astroviruses with a potential zoonotic transmission highlights the need to gain insights on their biology in order to prevent future health threats. This review focuses on the basic virology, pathogenesis, host response, epidemiology, diagnostic assays, and prevention strategies for HAstVs.

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“…Another study showed that AstV CP can bind to purified MBL and was able to inhibit the lectin pathway in addition to inhibiting C3 activation and MAC formation. 97 In ABO incompatible blood transfusion reactions or hemolytic diseases, E23A, a derivative of the AstV CP,…”

Section: Astrovirusmentioning

confidence: 99%

Viral-derived complement inhibitors: current status and potential role in immunomodulation

Zaraket

2016

Exp Biol Med (Maywood)

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The complement system is one of the body's major innate immune defense mechanisms in vertebrates. Its function is to detect foreign bodies and promote their elimination through opsonisation or lysis. Complement proteins play an important role in the immunopathogenesis of several disorders. However, excessive complement activation does not confer more protection but instead leads to several autoimmune and inflammatory diseases. With inappropriate activation of the complement system, activated complement proteins and glycoproteins may damage both healthy and diseased tissues. Development of complement inhibitors represents an effective approach in controlling dysregulated complement activity and reducing disease severity, yet few studies have investigated the nature and role of novel complement inhibitory proteins of viral origin. Viral complement inhibitors have important implications in understanding the importance of complement inhibition and their role as a promising novel therapeutic approach in diseases caused by dysregulated complement function. In this review, we discuss the role and importance of complement inhibitors derived from several viruses in the scope of human inflammatory and autoimmune diseases.

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Human astrovirus coat protein binds C1q and MBL and inhibits the classical and lectin pathways of complement activation

Cited by 57 publications

References 22 publications

Torque Teno Virus Viremia Load Size in Patients with Selected Congenital Defects of Innate Immunity

Torque Teno Virus Viremia Load Size in Patients with Selected Congenital Defects of Innate Immunity

Human Astroviruses

Viral-derived complement inhibitors: current status and potential role in immunomodulation

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