1 Rush St Luke's Medical Center, Department of Immunology and Microbiology, 1653 W. Congress Parkway, Chicago, IL 60612, USA
2 United States Army Medical Research Institute of Infectious Diseases, Division of Virology, 1425 Porter Street, Frederick, MD 21702-5011, USA
Correspondence
Gregory T. Spear
gspear{at}rush.edu
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ABSTRACT |
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INTRODUCTION |
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Mannose-binding lectin (MBL) is a C-type lectin found in serum with specificity for mannose, N-acetylglucosamine and fucose (Hansen & Holmskov, 1998). MBL has several important innate immune functions including initiation of the lectin complement pathway, opsonization of microbes for uptake by phagocytic cells and direct neutralization of some viruses (Jack et al., 2001
; Matsushita & Fujita, 2001
; Petersen et al., 2001
). MBL binds strongly to human immunodeficiency virus type 1 (HIV-1), and high-mannose N-linked glycans on the HIV-1 glycoprotein gp120 are critical for this interaction (Ezekowitz et al., 1989
; Hart et al., 2002
; Haurum et al., 1993
; Ohtani et al., 1999
; Saifuddin et al., 2000
). HIV-1 gp120 also binds to DC-SIGN, DC-SIGNR and cyanovirin-N through high-mannose N-linked glycans (Bashirova et al., 2001
; Bolmstedt et al., 2001
; Esser et al., 1999
; Geijtenbeek et al., 2000
). Since Ebola virus interacts with DC-SIGN, DC-SIGNR and cyanovirin-N, we hypothesized that the Ebola glycoprotein would also bind to MBL. This study assessed the ability of Ebola and Marburg virus glycoprotein-pseudotyped viruses to bind to immobilized MBL and to activate the lectin complement pathway. We also evaluated the ability of MBL to inhibit interaction between the Ebola virus glycoprotein and DC-SIGN. Virus pseudotyped with the envelope glycoprotein of vesicular stomatitis virus (VSV-G) was used as a control in these experiments, since both VSV and HIV particles pseudotyped with VSV-G are neutralized by the classical pathway of human complement (Beebe & Cooper, 1981
; DePolo et al., 2000
).
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METHODS |
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As described previously (Hart et al., 2003), supernatants from a human liver fibroblast cell line infected with recombinant vaccinia virus expressing human recombinant MBL (rMBL) were collected and rMBL was purified on a mannanSepharose 4B column. MBL was also purified from freshly frozen plasma as previously described (Suankratay et al., 1998
). Briefly, MBL was affinity isolated using mannan-coupled Sepharose, passed over protein ASepharose to remove residual immunoglobulins and concentrated. The concentration of MBL was determined by ELISA.
Preparation of pseudotyped viruses.
HIV particles lacking gp120/gp41 and pseudotyped with Ebola and Marburg envelope proteins were used in all experiments since filoviruses present a significant biohazard (Chan et al., 2000). Pseudotyped viruses were prepared by co-transfecting 293 cells using Lipofectamine (Gibco-BRL) with env-negative HIV plasmid pNL 4-3 (E) (ARRRP) expressing luciferase together with plasmids expressing either VSV-G (DePolo et al., 2000
), Marburg (Ravn strain), Marburg (Musoke strain) or Ebola (Zaire strain) envelope glycoproteins. The filovirus glycoprotein plasmids were kindly provided by Dr Connie Schmaljohn (US Army Medical Research Institute of Infectious Disease, Fort Detrick, MD, USA). Supernatants containing virus were collected after 2 days of incubation. Virus concentration was determined by ELISA for the HIV p24 core protein (AIDS Vaccine program, Frederik, MD, USA).
Binding of pseudotyped viruses to MBL.
Flat-bottomed, 96-well polystyrene tissue culture plates (Costar) were coated overnight with 100 µl of either BSA or rMBL (10 µg ml1) diluted in veronal-buffered saline (VBS-Ca: 5 mM veronal pH 7·5, 0·15 M NaCl and 10 mM CaCl2). Wells were blocked with 1 % BSA, washed with VBS-Ca and incubated for 4 h with 100 µl pseudotyped virus (8 ng p24 ml1) diluted in VBS-Ca. Wells were washed with VBS-Ca, bound viruses were lysed with 0·25 % Triton X-100 and p24 was detected by ELISA. The percentage of p24 bound for each virus was calculated as: [(p24 bound in MBL-coated wellsbackground binding to BSA-coated wells)/(input p24background binding)]x100.
Binding of pseudotyped viruses to DC-SIGN.
Virus pseudotyped with the Ebola envelope glycoprotein was pre-incubated with rMBL (010 µg p24 ml1) for 1 h at 37 °C before incubation with 1x106 DC-SIGN+ or DC-SIGN THP-1 cells for 3 h at 37 °C. Cells were washed, lysed with detergent (0·2 % Tween 20) and cell-bound virus was measured by p24 ELISA.
Measurement of lectin complement pathway activity.
Lectin pathway-dependent C4 deposition was assayed as previously described (Valdimarsson et al., 1998). Microtitre plate wells (Maxisorp Nunc) were coated overnight with 10 µg mannan ml1 and wells were then blocked with 1 % BSA. Sera diluted in buffer containing 20 mM Tris/HCl pH 7·4, 10 mM CaCl2, 1 M NaCl, 0·05 % Triton X-100 and 1 % BSA (100 µl per well) were incubated in wells overnight at 4 °C. Purified C4 (12 µg per well; Calbiochem) was added to each well and incubated for 1·5 h at 37 °C. Wells were washed, 8 ng biotinylated goat anti-human C4 antibody (Calbiochem) was added per well and wells were incubated at room temperature for 1 h. Wells were washed and streptavidinHRP (Biosource) was added to the wells for 45 min at 37 °C. After further washing, substrate was added and the absorbance at 405 nm was determined.
Complement neutralization of pseudotyped viruses.
Pseudotyped viruses were incubated with dilutions of NHPS, MDPS or heat-inactivated sera at 37 °C for 50 min. Treated virus (100 µl) was transferred to 48-well flat-bottomed culture plates containing 0·7x105 293 cells per well. Plates were centrifuged at 1000 g for 2 h at 25 °C to facilitate infection (Ying et al., 2004) and then incubated for 4 h at 37 °C. The viruscomplement mixture was replaced with fresh medium and cells were harvested after 40 h of culture. Luciferase activity in cells was measured and neutralization calculated by the formula: neutralization (%)=100(complement-treated luciferase units/heat-inactivated complement luciferase units)x100.
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RESULTS |
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Viruses pseudotyped with either Ebola, Marburg (Musoke) or Marburg (Ravn) glycoproteins were compared next using the highest concentration of complement (1 : 2 dilution of sera). The Ebola- and Marburg (Musoke)-pseudotyped viruses were 87 and 85 % neutralized, respectively, while Marburg (Ravn)-pseudotyped virus was 65 % neutralized by treatment with NHPS (Fig. 4d). In contrast, MDPS neutralized each pseudotyped virus at significantly lower levels than NHPS (Fig. 4d
).
To confirm that MBL plays a role in neutralizing the Ebola glycoprotein-pseudotyped virus, we assessed the effect on neutralization of reconstituting the lectin complement pathway in MDPS by adding MBL. Addition of 10 µg purified MBL ml1 to heat-inactivated MDPS did not increase neutralization of the Ebola glycoprotein-pseudotyped virus when compared with heat-inactivated MDPS alone (Fig. 5). In contrast, addition of MBL to MDPS significantly neutralized the pseudotyped virus when compared with MDPS alone (Fig. 5
).
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DISCUSSION |
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Filovirus infections are associated with both the inability to mount effective adaptive immune responses and downregulation of innate immune responses (Bray, 2001; Geisbert et al., 2003
; Mahanty & Bray, 2004
; Reed et al., 2004
; Sanchez et al., 2004
). While vaccination has been investigated as a way of boosting adaptive immune responses to filoviruses and increase survival during infection, few studies have evaluated innate immunity. Innate immune responses are an important early response by the host, since they can inhibit viral growth while simultaneously initiating and modulating adaptive immune responses (Baron et al., 2000
; Biron, 1998
; Biron et al., 1999
; Hackett, 2003
; Singh & Baron, 2000
). In the mouse model of Ebola, the innate immune response, and specifically type I interferon production, was shown to be important for protection (Bray, 2001
; Mahanty et al., 2003
), while the viral protein VP35 functions as an interferon antagonist (Basler et al., 2000
, 2003
). More recently, Warfield et al. (2004)
demonstrated a role for NK cells in protection when mice were vaccinated with Ebola virus-like particles. While these observations describe antiviral effects of the innate immune response, only a few studies have evaluated the role of the complement system. One study compared complement levels with Ebola virus-induced disease outcome (Zabavichene & Chepurnov, 2004
) and an association between complement activation and lethal outcome in guinea pigs was observed. Specifically, early activation followed by a steady decline in complement activity was associated with a lethal outcome. Takada and co-workers (Takada et al., 2003
; Takada & Kawaoka, 2003
) showed that complement component C1q mediated antibody-dependent enhancement of Ebola infection in vitro. In contrast, a potential beneficial role for complement in adaptive responses was demonstrated by Wilson et al. (2000)
, since complement boosted neutralization of Ebola by monoclonal antibodies. Similarly, in vitro neutralization of Marburg virus by specific monoclonal antibodies was dependent on complement (Hevey et al., 2003
). Interactions between filoviruses and the lectin or alternative complement pathways have not been investigated.
MBL recognizes a variety of clinically relevant pathogens by binding to repeating sugar structures found on exposed proteins (Ezekowitz, 2003). For example, MBL binds to influenza virus, herpes simplex virus type 2 and HIV through N-linked high-mannose carbohydrate structures on their respective glycoproteins (Anders et al., 1994
; Gadjeva et al., 2004
; Hartshorn et al., 1993
; Reading et al., 1995
; Saifuddin et al., 2000
). The GP1 and GP2 glycoproteins of filoviruses are heavily glycosylated and predicted to have both N-linked and O-linked carbohydrate structures (Feldmann et al., 1994
; Geyer et al., 1992
), although O-linked carbohydrates are rarely terminated with mannose residues. DC-SIGN and cyanovirin-N, which bind to N-linked high-mannose oligosaccharides, have been shown to bind to Ebola and Marburg glycoproteins (Alvarez et al., 2002
; Barrientos et al., 2003
, 2004a
, b
; Marzi et al., 2004
; Simmons et al., 2003
). A role for macrophage cell-surface C-type lectin in binding the virus has also been demonstrated (Takada et al., 2004
). In the current study, the existence of high-mannose N-linked carbohydrate structures on a filovirus envelope protein was supported by the demonstration that MBL binds to both Ebola and Marburg virus glycoproteins. Overall, binding of the Ebola and Marburg (Musoke) glycoprotein-pseudotyped viruses to MBL was similar to binding of HIV. There was less binding by Marburg (Ravn)-pseudotyped virus to MBL. These differences in binding may be due to different glycosylation patterns in the envelope glycoproteins. An analysis of GenBank sequences shows that the Ravn and Musoke strains are only 70 % homologous in amino acid sequence. Furthermore, while Ebola and Marburg viruses share a number of predicted N-linked glycosylation sites, there are also sites that differ between the two. Similarly, Marburg strains appear to share some N-linked sites but are divergent at other sites. As expected, the VSV-pseudotyped virus did not bind efficiently to MBL, presumably because VSV-G lacks high-mannose carbohydrate structures. VSV-G contains only two to six potential glycosylation sites (Coll, 1995
).
In this study, neutralization of filoviruses was dependent on complement activity since heat inactivation reduced neutralization. However, MBL has been shown to alter virus infectivity directly by mechanisms that are independent of complement activation. Thus, MBL neutralizes influenza A virus by blocking glycoprotein interactions with receptors and viral aggregation (Hartshorn et al., 1997; Saifuddin et al., 2000
). MBL could neutralize filoviruses by similar mechanisms. While several potential receptors have been proposed for Ebola, DC-SIGN and C-type lectins specific for galactose and N-acetylgalactosamine have been implicated as an Ebola-binding protein (Alvarez et al., 2002
; Takada et al., 2004
). In the absence of complement, MBL treatment of virus blocked the Ebola glycoprotein-mediated attachment to cells expressing DC-SIGN. During infection, MBL binding to circulating virus could effectively reduce viral infection of lectin-expressing cells, including dendritic cells that modulate later adaptive responses.
There is disagreement on the role of MBL in disease progression due to viral agents. For example, there are conflicting reports on the association between MBL variants and HIV infections (Ji et al., 2005). A large percentage of the population are MBL deficient and low MBL levels could have a significant impact on viral infection. Despite the ability of MBL to bind and inhibit filovirus glycoprotein-pseudotyped virus infection in vitro, natural disease in humans is characterized by explosive virus replication with high mortality. No study has evaluated MBL expression in the populations that have been afflicted with filovirus disease. The current study suggests that MBL levels in patients should be studied. Alternatively, filoviruses could avoid complement activity by a variety of ways (Spear et al., 2001
). Binding of MBL to virus and subsequent deposition of complement components on the viral membrane could lead to enhanced virus infection of cells that express complement receptors. Furthermore, as observed with other enveloped viruses, filoviruses may incorporate host complement control proteins that would limit the ability of complement to eliminate the cell-free virus.
In summary, we have demonstrated the ability of MBL, a recognition and effector molecule of the innate immune system, to bind to filovirus glycoproteins, resulting in antiviral activity. These findings suggest that human MBL may play important roles in innate immunity during filovirus infections such as direct inhibition of infection and inhibition of viral spread, as well as mediating opsonization and complement activation. Further studies are needed to evaluate the role of MBL and complement during filovirus infections.
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ACKNOWLEDGEMENTS |
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REFERENCES |
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![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Anders, E. M., Hartley, C. A., Reading, P. C. & Ezekowitz, R. A. (1994). Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin. J Gen Virol 75, 615622.[Abstract]
Baribaud, F., Pohlmann, S., Leslie, G., Mortari, F. & Doms, R. W. (2002). Quantitative expression and virus transmission analysis of DC-SIGN on monocyte-derived dendritic cells. J Virol 76, 91359142.
Baron, S., Singh, I., Chopra, A., Coppenhaver, D. & Pan, J. (2000). Innate antiviral defenses in body fluids and tissues. Antiviral Res 48, 7189.[CrossRef][Medline]
Barrientos, L. G., O'Keefe, B. R., Bray, M., Sanchez, A., Gronenborn, A. M. & Boyd, M. R. (2003). Cyanovirin-N binds to the viral surface glycoprotein, GP1,2 and inhibits infectivity of Ebola virus. Antiviral Res 58, 4756.[CrossRef][Medline]
Barrientos, L. G., Lasala, F., Delgado, R., Sanchez, A. & Gronenborn, A. M. (2004a). Flipping the switch from monomeric to dimeric CV-N has little effect on antiviral activity. Structure 12, 17991807.[CrossRef][Medline]
Barrientos, L. G., Lasala, F., Otero, J. R., Sanchez, A. & Delgado, R. (2004b). In vitro evaluation of cyanovirin-N antiviral activity, by use of lentiviral vectors pseudotyped with filovirus envelope glycoproteins. J Infect Dis 189, 14401443.[CrossRef][Medline]
Bashirova, A. A., Geijtenbeek, T. B., van Duijnhoven, G. C. & 10 other authors (2001). A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. J Exp Med 193, 671678.
Basler, C. F., Wang, X., Muhlberger, E., Volchkov, V., Paragas, J., Klenk, H. D., Garcia-Sastre, A. & Palese, P. (2000). The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc Natl Acad Sci U S A 97, 1228912294.
Basler, C. F., Mikulasova, A., Martinez-Sobrido, L., Paragas, J., Muhlberger, E., Bray, M., Klenk, H. D., Palese, P. & Garcia-Sastre, A. (2003). The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol 77, 79457956.
Beebe, D. P. & Cooper, N. R. (1981). Neutralization of vesicular stomatitis virus (VSV) by human complement requires a natural IgM antibody present in human serum. J Immunol 126, 15621568.
Biron, C. A. (1998). Role of early cytokines, including alpha and beta interferons (IFN-/
), in innate and adaptive immune responses to viral infections. Semin Immunol 10, 383390.[CrossRef][Medline]
Biron, C. A., Nguyen, K. B., Pien, G. C., Cousens, L. P. & Salazar-Mather, T. P. (1999). Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17, 189220.[CrossRef][Medline]
Bolmstedt, A. J., O'Keefe, B. R., Shenoy, S. R., McMahon, J. B. & Boyd, M. R. (2001). Cyanovirin-N defines a new class of antiviral agent targeting N-linked, high-mannose glycans in an oligosaccharide-specific manner. Mol Pharmacol 59, 949954.
Botos, I. & Wlodawer, A. (2003). Cyanovirin-N: a sugar-binding antiviral protein with a new twist. Cell Mol Life Sci 60, 277287.[CrossRef][Medline]
Bray, M. (2001). The role of the Type I interferon response in the resistance of mice to filovirus infection. J Gen Virol 82, 13651373.
Chan, S. Y., Speck, R. F., Ma, M. C. & Goldsmith, M. A. (2000). Distinct mechanisms of entry by envelope glycoproteins of Marburg and Ebola (Zaire) viruses. J Virol 74, 49334937.
Coll, J. M. (1995). The glycoprotein G of rhabdoviruses. Arch Virol 140, 827851.[CrossRef][Medline]
DePolo, N. J., Reed, J. D., Sheridan, P. L., Townsend, K., Sauter, S. L., Jolly, D. J. & Dubensky, T. W., Jr (2000). VSV-G pseudotyped lentiviral vector particles produced in human cells are inactivated by human serum. Mol Ther 2, 218222.[CrossRef][Medline]
Esser, M. T., Mori, T., Mondor, I., Sattentau, Q. J., Dey, B., Berger, E. A., Boyd, M. R. & Lifson, J. D. (1999). Cyanovirin-N binds to gp120 to interfere with CD4-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD4 binding site on gp120 or soluble CD4-induced conformational changes in gp120. J Virol 73, 43604371.
Ezekowitz, R. A. (2003). Role of the mannose-binding lectin in innate immunity. J Infect Dis 187, S335S339.[CrossRef][Medline]
Ezekowitz, R. A., Kuhlman, M., Groopman, J. E. & Byrn, R. A. (1989). A human serum mannose-binding protein inhibits in vitro infection by the human immunodeficiency virus. J Exp Med 169, 185196.
Feinberg, H., Mitchell, D. A., Drickamer, K. & Weis, W. I. (2001). Structural basis for selective recognition of oligosaccharides by DC- SIGN and DC-SIGNR. Science 294, 21632166.
Feldmann, H., Nichol, S. T., Klenk, H. D., Peters, C. J. & Sanchez, A. (1994). Characterization of filoviruses based on differences in structure and antigenicity of the virion glycoprotein. Virology 199, 469473.[CrossRef][Medline]
Gadjeva, M., Paludan, S. R., Thiel, S. & 8 other authors (2004). Mannan-binding lectin modulates the response to HSV-2 infection. Clin Exp Immunol 138, 304311.[CrossRef][Medline]
Geijtenbeek, T. B., Kwon, D. S., Torensma, R. & 9 other authors (2000). DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells [see comments]. Cell 100, 587597.[CrossRef][Medline]
Geisbert, T. W., Hensley, L. E., Larsen, T. & 7 other authors (2003). Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am J Pathol 163, 23472370.
Geyer, H., Will, C., Feldmann, H., Klenk, H. D. & Geyer, R. (1992). Carbohydrate structure of Marburg virus glycoprotein. Glycobiology 2, 299312.[Abstract]
Hackett, C. J. (2003). Innate immune activation as a broad-spectrum biodefense strategy: prospects and research challenges. J Allergy Clin Immunol 112, 686694.[CrossRef][Medline]
Hansen, S. & Holmskov, U. (1998). Structural aspects of collectins and receptors for collectins. Immunobiology 199, 165189.[Medline]
Hart, M. L., Saifuddin, M., Uemura, K., Bremer, E. G., Hooker, B., Kawasaki, T. & Spear, G. T. (2002). High mannose glycans and sialic acid on gp120 regulate binding of mannose-binding lectin (MBL) to HIV type 1. AIDS Res Hum Retroviruses 18, 13111317.[CrossRef][Medline]
Hart, M. L., Saifuddin, M. & Spear, G. T. (2003). Glycosylation inhibitors and neuraminidase enhance human immunodeficiency virus type 1 binding and neutralization by mannose-binding lectin. J Gen Virol 84, 353360.
Hartshorn, K. L., Sastry, K., White, M. R., Anders, E. M., Super, M., Ezekowitz, R. A. & Tauber, A. I. (1993). Human mannose-binding protein functions as an opsonin for influenza A viruses. J Clin Invest 91, 14141420.[Medline]
Hartshorn, K. L., White, M. R., Shepherd, V., Reid, K., Jensenius, J. C. & Crouch, E. C. (1997). Mechanisms of anti-influenza activity of surfactant proteins A and D: comparison with serum collectins. Am J Physiol 273, L1156L1166.[Medline]
Haurum, J. S., Thiel, S., Jones, I. M., Fischer, P. B., Laursen, S. B. & Jensenius, J. C. (1993). Complement activation upon binding of mannan-binding protein to HIV envelope glycoproteins. AIDS 7, 13071313.[Medline]
Hevey, M., Negley, D. & Schmaljohn, A. (2003). Characterization of monoclonal antibodies to Marburg virus (strain Musoke) glycoprotein and identification of two protective epitopes. Virology 314, 350357.[CrossRef][Medline]
Jack, D. L., Klein, N. J. & Turner, M. W. (2001). Mannose-binding lectin: targeting the microbial world for complement attack and opsonophagocytosis. Immunol Rev 180, 8699.[CrossRef][Medline]
Ji, X., Gewurz, H. & Spear, G. T. (2005). Mannose binding lectin (MBL) and HIV. Mol Immunol 42, 145152.[CrossRef][Medline]
Lin, G., Simmons, G., Pohlmann, S. & 8 other authors (2003). Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR. J Virol 77, 13371346.[CrossRef][Medline]
Mahanty, S. & Bray, M. (2004). Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis 4, 487498.[CrossRef][Medline]
Mahanty, S., Gupta, M., Paragas, J., Bray, M., Ahmed, R. & Rollin, P. E. (2003). Protection from lethal infection is determined by innate immune responses in a mouse model of Ebola virus infection. Virology 312, 415424.[CrossRef][Medline]
Marzi, A., Gramberg, T., Simmons, G. & 12 other authors (2004). DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus. J Virol 78, 1209012095.
Matsushita, M. & Fujita, T. (2001). Ficolins and the lectin complement pathway. Immunol Rev 180, 7885.[CrossRef][Medline]
Ohtani, K., Suzuki, Y., Eda, S. & 7 other authors (1999). High-level and effective production of human mannan-binding lectin (MBL) in Chinese hamster ovary (CHO) cells. J Immunol Methods 222, 135144.[CrossRef][Medline]
Petersen, S. V., Thiel, S. & Jensenius, J. C. (2001). The mannan-binding lectin pathway of complement activation: biology and disease association. Mol Immunol 38, 133149.[CrossRef][Medline]
Reading, P. C., Hartley, C. A., Ezekowitz, R. A. & Anders, E. M. (1995). A serum mannose-binding lectin mediates complement-dependent lysis of influenza virus-infected cells. Biochem Biophys Res Commun 217, 11281136.[CrossRef][Medline]
Reed, D. S., Hensley, L. E., Geisbert, J. B., Jahrling, P. B. & Geisbert, T. W. (2004). Depletion of peripheral blood T lymphocytes and NK cells during the course of Ebola hemorrhagic fever in cynomolgus macaques. Viral Immunol 17, 390400.[CrossRef][Medline]
Saifuddin, M., Hart, M. L., Gewurz, H., Zhang, Y. & Spear, G. T. (2000). Interaction of mannose-binding lectin with primary isolates of human immunodeficiency virus type 1. J Gen Virol 81, 949955.
Sanchez, A., Trappier, S. G., Mahy, B. W., Peters, C. J. & Nichol, S. T. (1996). The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc Natl Acad Sci U S A 93, 36023607.
Sanchez, A., Lukwiya, M., Bausch, D., Mahanty, S., Sanchez, A. J., Wagoner, K. D. & Rollin, P. E. (2004). Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. J Virol 78, 1037010377.
Simmons, G., Wool-Lewis, R. J., Baribaud, F., Netter, R. C. & Bates, P. (2002). Ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence. J Virol 76, 25182528.
Simmons, G., Reeves, J. D., Grogan, C. C. & 10 other authors (2003). DC-SIGN and DC-SIGNR bind Ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology 305, 115123.[CrossRef][Medline]
Singh, I. P. & Baron, S. (2000). Innate defences against viraemia. Rev Med Virol 10, 395403.[CrossRef][Medline]
Spear, G. T., Hart, M., Olinger, G. G., Hashemi, F. B. & Saifuddin, M. (2001). The role of the complement system in virus infections. Curr Top Microbiol Immunol 260, 229245.[Medline]
Suankratay, C., Zhang, X. H., Zhang, Y., Lint, T. F. & Gewurz, H. (1998). Requirement for the alternative pathway as well as C4 and C2 in complement-dependent hemolysis via the lectin pathway. J Immunol 160, 30063013.
Sullivan, N. J., Peterson, M., Yang, Z. Y., Kong, W. P., Duckers, H., Nabel, E. & Nabel, G. J. (2005). Ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway. J Virol 79, 547553.
Takada, A. & Kawaoka, Y. (2001). The pathogenesis of Ebola hemorrhagic fever. Trends Microbiol 9, 506511.[CrossRef][Medline]
Takada, A. & Kawaoka, Y. (2003). Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol 13, 387398.[CrossRef][Medline]
Takada, A., Feldmann, H., Ksiazek, T. G. & Kawaoka, Y. (2003). Antibody-dependent enhancement of Ebola virus infection. J Virol 77, 75397544.
Takada, A., Fujioka, K., Tsuiji, M. & 7 other authors (2004). Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry. J Virol 78, 29432947.
Valdimarsson, H., Stefansson, M., Vikingsdottir, T., Arason, G. J., Koch, C., Thiel, S. & Jensenius, J. C. (1998). Reconstitution of opsonizing activity by infusion of mannan-binding lectin (MBL) to MBL-deficient humans. Scand J Immunol 48, 116123.[CrossRef][Medline]
Warfield, K. L., Perkins, J. G., Swenson, D. L., Deal, E. M., Bosio, C. M., Aman, M. J., Yokoyama, W. M., Young, H. A. & Bavari, S. (2004). Role of natural killer cells in innate protection against lethal Ebola virus infection. J Exp Med 200, 169179.
Wilson, J. A., Hevey, M., Bakken, R., Guest, S., Bray, M., Schmaljohn, A. L. & Hart, M. K. (2000). Epitopes involved in antibody-mediated protection from Ebola virus. Science 287, 16641666.
Wu, L., Martin, T. D., Carrington, M. & KewalRamani, V. N. (2004). Raji B cells, misidentified as THP-1 cells, stimulate DC-SIGN-mediated HIV transmission. Virology 318, 1723.[CrossRef][Medline]
Ying, H., Ji, X., Hart, M. L., Gupta, K., Saifuddin, M., Zariffard, M. R. & Spear, G. T. (2004). Interaction of mannose-binding lectin with HIV type 1 is sufficient for virus opsonization but not neutralization. AIDS Res Hum Retroviruses 20, 327335.[CrossRef][Medline]
Zabavichene, N. M. & Chepurnov, A. A. (2004). Dynamics of complement hemolytic activity in experimental Ebola infection. Vopr Virusol 49, 2125 (in Russian).[Medline]
Received 23 May 2005;
accepted 3 June 2005.
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