Biomedical subjects

C Mold

Publications and source records attributed to C Mold.

At least 37 records · Page 2Linked to original sources

PubMed1996

Localization of classical and alternative pathway regulatory activity within the decay-accelerating factor.

Decay-accelerating factor (DAF) is a cell-associated C regulatory protein that protects host cells from autologous C attack. It functions intrinsically in host cell surface membranes to rapidly dissociate autologous classical and alternative pathway C3 convertases whenever these amplifying enzymes assemble on host cell surfaces. It is composed of four contiguous approximately 70 amino acid long regions termed short consensus repeats (SCRs) that share homology with similar units in other C3 convertase regulatory proteins. It is attached to the cell surface membrane by a glycoinositol phospholipid (GPI) anchor that is added posttranslationally. In this study, we prepared rGPI-anchored DAF proteins devoid of individual SCRs. We then incorporated the GPI-anchored products into sheep erythrocyte (Esh) hemolytic intermediates and examined their abilities to intrinsically regulate classical or alternative pathway activation. We found that classical pathway C3 convertase regulatory function resides within SCR-2 and SCR-3, while alternative pathway C3 convertase regulatory function resides within SCR-2, -3, and -4. Functional comparisons of the variant DAF proteins in fluid phase C3 activation assays established that the differences reflect domain-specific interactions rather than changes in the spatial arrangement of SCRs above the cell surface. In accordance with these findings, we found that variant DAF molecules containing SCR-1, -2, and -3, but not SCR-4, function to selectively inhibit classical pathway activation.

Animals↗

PubMed1996

Complement-dependent binding of C-reactive protein complexes to human erythrocyte CR1.

C-reactive protein (CRP) is an acute phase serum protein that binds to phosphocholine (PC) on phospholipids and polysaccharides and to protein components of chromatin and small nuclear ribonucleoproteins. Complexes between CRP and ligands activate complement and bind to receptors on phagocytic cells. Although complement is required for CRP-mediated clearance or phagocytosis of ligand-coated erythrocytes, the participation of complement and complement receptors in clearance of soluble CRP complexes has not been examined. We have used PC-conjugated BSA to prepare complexes containing either IgG antibody or CRP. We found similar complement-mediated binding of both types of complexes to human erythrocyte complement receptors (CR1, CD35). We also found that serum deficient in C4A or C4B supported binding of CRP and IgG complexes to erythrocytes. These findings indicate that complexes between CRP and soluble ligands may be cleared by the erythrocyte CR1 pathway described for soluble immune complexes.

Antigen-Antibody Complex↗

PubMed1995

C-reactive protein binds to Fc gamma RI in transfected COS cells.

C-Reactive protein (CRP) is an acute phase serum protein in man that binds to certain bacterial polysaccharides and to components exposed on damaged cells. CRP is bound by receptors on phagocytic cells and functions as an opsonin for its ligands. Interactions of CRP with a specific CRP receptor (CRP-R) and with the high affinity receptor for IgG, Fc gamma RI, on monocytic cells have previously been demonstrated. It was not possible to fully characterize CRP binding to Fc gamma RI in these studies, since cells and cell lines expressing Fc gamma RI also have the CRP-R. In the present study we examined the interaction of CRP with Fc gamma RI in COS-7 cells transfected with a cDNA encoding this receptor. Expression of Fc gamma RI and specific CRP binding to transfected cells were demonstrated by flow cytometry. By two-color analysis, the cell population binding CRP was the same as the population that bound the Fc gamma RI-specific mAb 10.1 and 32.2 CRP inhibited the binding of radiolabeled IgG1 and IgG4 by up to 60%. A CRP molecule that was mutated in the amino acid sequence homologous to the IgG sequence proposed to interact with Fc gamma RI failed to bind to transfected cells, but retained the ability to bind to the CRP-R on monocytic cells. These studies confirm the binding of CRP to Fc gamma RI and identify a site on CRP that is essential for this binding.

Amino Acid Sequence↗

PubMed1995

Complement activation during painful crisis in sickle cell anemia.

Previous studies documented complement activation in sickle cell disease patients and suggested that this contributes to increased risk of infection. We have demonstrated alternative pathway activation initiated by membrane phospholipid changes which occur in sickled erythrocytes. The present studies compared complement activation products in serial samples from sickle cell anemia patients at baseline and during hospitalization for painful crisis to examine the correlation between complement activation and disease activity. Plasma concentrations of Bb, C4d, and C3a were measured as well as C3 bound to erythrocytes. Patients were subdivided into those with continuous pain and those with intermittent painful episodes. In patients with intermittent pain, there was little evidence of complement activation at baseline and increased plasma concentrations of Bb and C3a during painful crisis. Elevated C3a and C4d levels were observed in patients with continuous pain regardless of hospitalization status, suggesting a continuous underlying inflammatory process in these patients.

Acute Disease↗

PubMed1995

Expression and radiolabeling of human C-reactive protein in baculovirus-infected cell lines and Trichoplusia ni larvae.

Human C-reactive protein (CRP) is a member of the pentraxin family of proteins which are molecules composed of five identical subunits arranged in a planar configuration. In the present study a human CRP cDNA clone was ligated into the baculovirus vector pVL1393 which was used to establish a recombinant strain of BaculoGold Autographa californica multiple nuclear polyhedrosis virus containing the coding and leader sequence for human CRP (designated AcMNPV-CRP). Synthesis and secretion of CRP were studied after infection of TN5B1-4 and Sf-9 cells with AcMNPV-CRP. Accumulation of CRP but not other proteins in the medium over the course of infection suggested that CRP was actively secreted. Analysis by gel filtration chromatography and by SDS-PAGE demonstrated an intact pentamer composed of subunits of the appropriate molecular mobility. The structural integrity of the recombinant protein was further established by the ability of the product to bind to phosphocholine in a calcium-dependent manner, a property which is restricted to the intact pentamer. Functional studies of complement activation, binding to mononuclear phagocytic cells, and reactivity with a panel of monoclonal antibodies were also consistent with structural and functional integrity of the recombinant molecule. Infection of Trichoplusia ni larvae with AcMNPV-CRP also resulted in the production of functional recombinant protein. This method has the advantage of producing larger amounts of protein at lower cost than tissue culture. An additional advantage is the ability to metabolically label CRP through feeding the larvae on an [35S]methionine-containing diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Expression of rabbit C-reactive protein in transgenic mice.

C-reactive protein (CRP) is a prototypic acute phase reactant in humans and rabbits whose serum concentration can increase up to 1000-fold following an acute inflammatory stimulus. CRP binds to many phosphate ester-containing compounds including phosphorylcholine, nucleotides, chromatin and snRNP. To examine the in vivo function of this protein, we produced transgenic mice capable of significant CRP synthesis. In contrast to most other vertebrates, mice synthesize CRP in only trace amounts. The transgenic animals express rabbit CRP from either the phosphoenolpyruvate carboxykinase promoter (PEPCK-CRP) or the mouse metallothionein I promoter (MT-CRP). Manipulating the diet in one of the PEPCK-CRP lines led to a rise in serum CRP levels from < 5 mu g/mL to 100-200 mu g/mL over a period of 2 days. The two MT-CRP lines examined expressed CRP constitutively which could be further elevated 2-4-fold following an inflammatory stimulus. Transgenic CRP bound phosphorylcholine was pentameric, had a circulating half-life of 30-60 min and was capable of activating mouse complement when bound to a ligand. We conclude that these transgenic lines express CRP with many of the properties of authentic rabbit CRP, and that the expression of CRP can be controlled to be dependent or independent of the acute phase response.

Acute-Phase Reaction↗

PubMed1995

Hyperoxic suppression of Fc-gamma receptor-mediated phagocytosis by isolated murine pulmonary macrophages.

Lower respiratory tract exposure to high oxygen (O2) concentrations is known to induce changes in pulmonary function through effects on several cell types located within the lung parenchyma, including pulmonary macrophages (PM). We studied the effects of hyperoxic exposure on phagocytosis via Fc-gamma receptors (FcR) on isolated murine PM. PM cultured in hyperoxic conditions exhibited little change in ingestion via FcR for up to 96 h, compared with significant increases in ingestion by PM cultured in 21% O2 over the same time period. This suppression was reversible and occurred whether 50 or 100% O2 concentrations were used for hyperoxic exposure. Addition of the potent macrophage-activating agent interferon-gamma (IFN-gamma) to cultured PM further increased FcR-mediated phagocytosis in normoxic PM but had no effect on PM cultured in 100% O2. Analysis of FcR expression by flow cytometry using monoclonal antibodies specific for two different FcR classes revealed that culture in normoxic conditions increased surface expression of both FcR classes. Hyperoxic culture inhibited up-regulation of the high-affinity FcR but did not affect low-affinity FcR up-regulation, suggesting that hyperoxic effects were not due solely to effects on regulation of FcR expression. However, hyperoxic exposure completely suppressed FcR-mediated actin polymerization. These findings suggest that hyperoxic exposure impairs PM ability to increase FcR-mediated phagocytic activity after appropriate stimulation, which could impair the lung's defenses against infection.

Actins↗

PubMed1994

Sublytic complement attack exposes C-reactive protein binding sites on cell membranes.

C-reactive protein (CRP) is an acute phase serum protein synthesized by the liver. CRP has been localized to acute inflammatory sites and has been postulated to facilitate the removal of damaged cells. CRP binds to a number of ligands that may be present in inflammatory sites, and the extent to which individual ligands are involved in its binding to tissue sites is unknown. Complement activation is important in the tissue damage in many inflammatory conditions causing cell membrane damage and recruitment of inflammatory cells. This paper describes the binding of CRP to complement-damaged cell membranes. Raji cells activate the alternative complement pathway resulting in the deposition of C3b and membrane attack complexes (MAC) on the cell membrane. However, Raji cells are relatively resistant to killing by human complement. Treatment of Raji cells with human serum led to calcium-dependent phosphocholine-inhibitable CRP binding. CRP binding was eliminated by depletion of C3, C5, or C8 and reduced by depletion of C9 from serum. CRP binding preceded cell death and co-localized with MAC on cell membranes. CRP binding to complement-treated liposomes required phosphatidylcholine in addition to the MAC indicating that membrane phospholipids rather than the MAC proteins provide the binding sites for CRP. However, for both liposomes and Raji cells disruption of the lipid bilayer by complement attack was required for CRP binding to occur. These results support the hypothesis that CRP binding at sites of inflammation may be mediated by exposed phospholipids on damaged cell membranes.

Binding Sites↗

PubMed1994

Quantitative analysis of C4b dimer binding to distinct sites on the C3b/C4b receptor (CR1).

The complement receptor CR1 (CD35) is a transmembrane protein composed in its extracellular portion of short consensus repeats (SCR 1-30) organized into four long homologous repeats (LHR-A, LHR-B, LHR-C, and LHR-D). Each LHR, except LHR-D, contains a binding site for C3b and/or C4b within its first four SCR. The binding reaction between CR1 and soluble dimers of C4b (C4b2) was analyzed using the native receptor on human erythrocytes and full-length recombinant CR1 expressed in stably transfected Chinese hamster ovary (CHO) cells. CR1 mutants expressed similarly were used to determine the SCR of LHR-A required for C4b2 binding and the potential of C3b binding sites in CR1 to bind C4b2. Erythrocyte CR1, CHO cells expressing full-length recombinant CR1 (ABCD), constructs ACD, and SCR(1-4)D each bound C4b2 with similar affinities (Kd, approximately 4 x 10(-7) M). Construct SCR(1-2)D bound C4b2 with lower affinity (Kd, 1.4 x 10(-6) M) indicating that SCR(1-4) are required for a fully functional C4b2 binding site. Construct SCR(15-18)D, which contains a C3b site, also bound C4b2 with lower affinity (Kd 1.2 x 10(-6) M) than its binding to C3b dimers. Constructs SCR(15-16)D and D did not bind C4b2. Each CR1 construct that bound C4b2 functioned as a cofactor for factor I-mediated cleavage to C4d.

Animals↗

PubMed1994

Decreased autoantibody levels and enhanced survival of (NZB x NZW) F1 mice treated with C-reactive protein.

C-Reactive protein (CRP) is the prototypic acute-phase serum protein in man. On the basis of its binding specificities and activities, it has been proposed that CRP facilities the removal of nuclear material released from damaged cells. To determine whether such a process could alter the development of autoimmunity to nuclear antigens, the effect of CRP on autoimmune disease in the (NZB x NZW) F1 mouse model of systemic lupus erythematosus was tested. Mice were injected with chromatin bound to latex beads in the presence or absence of bound CRP. CRP treatment significantly prolonged survival of mice injected with chromatin-coated beads. CRP also produced a transient decrease in IgG antibody levels to histones, DNA, and DNP, suggesting a general suppressive effect on ongoing antibody responses. To determine whether CRP would affect chromatin clearance, the effect of CRP on nucleosome core particle clearance was tested in BALB/c mice. CRP pretreatment did not alter the rate of clearance or organ localization of nucleosome core particles. These findings indicate that CRP can modify the course of autoimmune disease possibly by preventing the exposure of nuclear antigens to the immune system.

Animals↗

PubMed1994

Growth of group B streptococci in human serum leads to increased cell surface sialic acid and decreased activation of the alternative complement pathway.

Group B streptococcus type III is a major cause of neonatal death. The terminal sialic acid moiety of the group B streptococcus type specific capsule has been shown to be an important virulence factor. We demonstrate here that bacteria grown in human serum have increased cell surface sialic acid content compared with cells grown in common laboratory media. This sialic acid was removed by incubation with neuraminidase, showing that it was on the bacterial surface. Serum-dependent sialylation was dependent on metabolic activity, as the addition of chloramphenicol reduced the amount of added sialic acid by more than 90%. Probing the cell surface with an antibody specific for group B streptococcus type III capsular sialic acid showed an increase in antibody binding after growth in human serum. This effect could be lowered by incubating serum-grown cells in neuraminidase prior to antibody exposure. A group B streptococcus mutant that when grown in laboratory media lacks cell surface sialic acid showed significant cell surface sialic acid when grown in human serum. This increase was associated with a significantly decreased ability to bind C3 and hence activate the alternative complement pathway.

Blood↗

PubMed1993

Activation of the alternative complement pathway by exposure of phosphatidylethanolamine and phosphatidylserine on erythrocytes from sickle cell disease patients.

Deoxygenation of erythrocytes from sickle cell anemia (SCA) patients alters membrane phospholipid distribution with increased exposure of phosphatidylethanolamine (PE) and phosphatidylserine (PS) on the outer leaflet. This study investigated whether altered membrane phospholipid exposure on sickle erythrocytes results in complement activation. In vitro deoxygenation of sickle but not normal erythrocytes resulted in complement activation measured by C3 binding. Additional evidence indicated that this activation was the result of the alterations in membrane phospholipids. First, complement was activated by normal erythrocytes after incubation with sodium tetrathionate, which produces similar phospholipid changes. Second, antibody was not required for complement activation by sickle or tetrathionate-treated erythrocytes. Third, the membrane regulatory proteins, decay-accelerating factor (CD55) and the C3b/C4b receptor (CD35), were normal on sickle and tetrathionate-treated erythrocytes. Finally, insertion of PE or PS into normal erythrocytes induced alternative pathway activation. SCA patients in crisis exhibited increased plasma factor Bb levels compared with baseline, and erythrocytes isolated from hospitalized SCA patients had increased levels of bound C3, indicating that alternative pathway activation occurs in vivo. Activation of complement may be a contributing factor in sickle crisis episodes, shortening the life span of erythrocytes and decreasing host defense against infections.

Anemia, Sickle Cell↗

PubMed1992

Serum amyloid P component binds to histones and activates the classical complement pathway.

Two members of the pentraxin family of proteins, C-reactive protein (CRP) and serum amyloid P component (SAP), bind to chromatin and may be involved in the solubilization and clearance of nuclear material. Previous studies demonstrated that CRP binding to chromatin is mediated by histones. SAP differs from CRP in being able to bind to DNA, but SAP binding to histones has not been reported. CRP is an activator of the classical C pathway, and C-dependent cleavage of chromatin in the presence of CRP and serum has been shown. Oligomers of SAP have recently been found to bind to C1q and consume total C and C4, indicating that SAP can activate C as well. The present study examined CRP and SAP binding to histones H1 and H2A and C activation after binding. SAP binding to histones H1 and H2A was observed as well as SAP binding to chromatin. In contrast to CRP, SAP binding to chromatin did not require H1. SAP partially inhibited CRP binding to chromatin and to H1. However, neither pentraxin inhibited binding of the other to H2A. Binding of either CRP or SAP to H2A activated C in SAP-depleted serum leading to the deposition of C4 and C3. C activation required C1q and produced C4d indicating that it occurred through the classical pathway. These findings demonstrate that CRP and SAP share histone as well as chromatin binding, and that both pentraxins can activate the classical C pathway after ligand binding.

Animals↗

PubMed1991

C-reactive protein receptors on the human monocytic cell line U-937. Evidence for additional binding to Fc gamma RI.

C-reactive protein (CRP) is an acute-phase protein that binds to components of damage tissue, activates C, and stimulates phagocytic cells. CRP binding to receptors on monocytic and polymorphonuclear phagocytes has been shown. Recently, CRP-binding proteins of 38 to 40 kDa and 57 to 60 kDa have been identified on the human promonocyte cell line U-937 and the mouse macrophage cell line PU5 1.8, respectively. However, analysis of CRP binding to these cells and to peripheral blood leukocytes suggests that additional CRP receptor sites may be present. Because many studies have shown interactions between CRP binding and IgG binding to leukocytes, we have examined further the CRP binding sites on U-937 cells and determined their relationship to the FcR for IgG (Fc gamma R) expressed on these cells. Our results demonstrate specific saturable binding of CRP to peripheral blood monocytes and U-937 cells, which is readily inhibited by aggregated IgG. Monomeric IgG, which binds specifically to Fc gamma RI, inhibited a maximum of 20% of CRP binding to these cells. mAb 197 and mAb IV.3, which block IgG binding to Fc gamma RI and Fc gamma RII, respectively, failed to inhibit CRP binding to U-937 cells. Two CRP-binding molecules were identified by precipitation of lysates from surface-labeled U-937 cells and cross-linking experiments. One of these had a molecular mass of 43 to 45 kDa, similar to the molecule previously described as the CRPR on U-937 cells. The other had the same mobility by SDS-PAGE as Fc gamma RI. The identity of this protein with Fc gamma RI was confirmed by the ability of both IgG-Sepharose and CRP-Sepharose to preclear the protein from cell lysates and by inhibition of binding to both IgG-Sepharose and CRP-Sepharose by anti-Fc gamma RI mAb 197.

Antigens, Differentiation↗

PubMed1990

The influence of membrane components on regulation of alternative pathway activation by decay-accelerating factor.

Decay-accelerating factor (DAF) is a C regulatory protein which functions in membranes to inhibit autologous C activation on cell surfaces. A liposome model was used to study the mechanism of DAF action and examine the effects of membrane-bound glycophorin and LPS on the regulatory activity of DAF. Liposomes were incubated in MgEGTA-treated human serum and activation of the alternative pathway measured by C3b binding. Liposomes composed of phosphatidylcholine, phosphatidylethanolamine, and cholesterol activated the alternative pathway in proportion to their content of PE. Incorporation of 10(-7) mol/mol phospholipid of either human E or HeLa cell-derived DAF inhibited C activation by liposomes containing 40% phosphatidylethanolamine by 50%, an efficiency comparable to that observed in intact E. HeLa DAF that had been treated with phosphatidylinositol-specific phospholipase C to remove its glycolipid anchor had no effect on C activation by liposomes at concentrations as high as 10(-5) mol/mol phospholipid. Incorporation of DAF into liposomes prepared with bound C3b inhibited the deposition of additional C3b by C3bBbP. However, the incorporated DAF increased the amount of Bb generated from B in the presence of D indicating that accelerated decay of the convertase was the primary effect of DAF. Similarly, treatment of intact human E with anti-DAF decreased the amount of Bb generated by the alternative pathway convertase. To study the effects of other membrane components on DAF activity, liposomes were prepared with purified human glycophorin A or LPS. In glycophorin liposomes the presence of PE was required to activate the alternative pathway and DAF inhibited this activation. In contrast, LPS liposomes bound C3b independently of PE and the incorporation of DAF had no effect. These results demonstrate that within a membrane, DAF's inhibitory activity on the alternative pathway C3 convertase is mediated independently of other membrane proteins, that in this model the major activity of DAF is to accelerate convertase decay, and that the presence of other membrane molecules that may serve as C3 acceptors can circumvent DAF function.

CD55 Antigens↗

PubMed1990

Identification of a polypeptide sequence that mediates nuclear localization of the acute phase protein C-reactive protein.

C-reactive protein (CRP) is the prototypic human acute phase serum protein. CRP binds to several nuclear Ag including chromatin, histones, and small nuclear ribonucleoproteins. Binding to sites of tissue inflammation and the nuclei of inflammatory cells has been demonstrated in vivo. We also noticed significant similarity between CRP and nucleoplasmin, a molecule with nuclear localization activity. We therefore decided to test whether CRP was capable of nuclear localization. CRP and the control protein human serum albumin were FITC-conjugated and microinjected into living VERO cells. The cells were incubated at 37 degrees C for 15 min and then examined by fluorescence microscopy. Nuclear localization of CRP but not albumin was rapid and a high nuclear to cytoplasmic ratio was seen, consistent with active nuclear transport. Incubation at reduced temperature inhibited nuclear uptake by CRP. A synthetic peptide, RKSLKK, from the CRP sequence, when coupled to FITC-albumin, also mediated nuclear localization. Nuclear localization of the related protein, serum amyloid P component, was also seen and a homologous nuclear localization signal was identified. Because CRP was previously demonstrated to inhibit RNA transcription and enhance chromatin degradation it is proposed that CRP may play a unique role in injured cells to alter processing of damaged nuclei. Biochemical, structural and sequence comparisons between the CRP/serum amyloid P component family of proteins (pentraxins) and the nucleoplasmin/B23 family of proteins showed regions of sequence homology that may be related to their shared cyclic pentameric structure.

Amino Acid Sequence↗

PubMed1989

Effect of membrane phospholipids on activation of the alternative complement pathway.

Although some of the membrane glycoproteins that serve as activators or regulators of C activation have been identified, the influence of membrane lipids has not been studied extensively. A model of alternative C pathway activation was established using liposomes composed of cholesterol and synthetic phospholipids. Liposomes containing phosphatidylcholine (PC) as the sole phospholipid did not activate C as measured by C3 binding after incubation in normal human serum containing 2.5 mM MgCl2 and 10 mM EGTA. When phosphatidylethanolamine (PE) was included as 20% or more of the phospholipid, C3 binding was observed. C3 binding to liposomes was inhibited by salicylhydroxamic acid indicating binding through the C3 thioester bond. The phospholipid composition did not influence C3 binding to liposomes in an unregulated system of C3, B, D, and P indicating equivalent C3b binding sites on activating and nonactivating liposomes. When the regulatory proteins H and I were added to the other components, liposomes containing PE bound three times more C3 than PC liposomes suggesting that the phospholipid affects C3 regulation. This was tested directly in a radiolabeled H binding assay. In the presence of equal amounts of C3b, PC liposomes showed a greater number of high affinity H binding sites than PE liposomes. Using different PE derivatives, C activation could be directly related to the phospholipid polar head group. Liposomes containing PE, trinitrophenyl-PE or monomethyl-PE did activate the alternative C pathway, whereas those containing dimethyl-PE, PC, or phosphatidylserine did not. These studies provide evidence that primary and secondary amino groups on lipid membranes can decrease the interaction between H and C3b and provide sites for alternative pathway activation.

Complement Activation↗

PubMed1988

Epstein-Barr virus regulates activation and processing of the third component of complement.

Serum incubated with purified EBV was found to contain C3 cleavage fragments characteristic of C3c. Since the cofactors necessary for such cleavage of C3b by factor I are not normally present in serum, EBV was tested for factor I cofactor activity. Purified EBV from both human and marmoset EBV-producing cell lines was found to act as a cofactor for the factor I-mediated breakdown C3b to iC3b and iC3b to C3c and C3dg. EBV also acted as a cofactor for the factor I-mediated cleavage of C4b to iC4b and iC4b to C4c and C4d. EBV from both the human and marmoset cell lines accelerated the decay of the alternative pathway C3 convertase. The classical pathway C3 convertase was unaffected. Multiple lines of evidence eliminated the possibility that marmoset or human CR1 was responsible for the functional activities of EBV preparations. The spectrum of activities was different from CR1 in that EBV and EBV-expressing cell lines failed to rosette with C3b or particles bearing C3b, the primary functional assay for CR1, and EBV did not accelerate classical pathway C3 convertase decay, another property of CR1. In addition, CR1 could not be detected immunologically on marmoset or human EBV-expressing cells and mAbs to CR1 failed to alter EBV-produced decay acceleration and factor I cofactor activities, although the antibodies blocked the same CR1-dependent functional activities. The multiple complement regulatory activities exhibited by purified EBV derived from human and marmoset cells differ from those of any of the known C3 or C4 regulatory proteins. These various activities would be anticipated to provide survival value for the virus by subverting complement- and cell-dependent host defense mechanisms.

Animals↗