1 Department of Medicine, Sections of Hematology/Oncology, Boston University School of Medicine, EBRC 414, 650 Albany Street, Boston, MA 02118, USA
2 Center for HIV/AIDS Care and Research, Boston University Medical Center, Boston, MA, USA
3 Department of Pathology, Washington University School of Medicine, St Louis, MO, USA
4 Department of Immunology and Microbiology, University of Southern Denmark, Odense, Denmark
Correspondence
Kevan L. Hartshorn
Khartsho{at}bu.edu
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ABSTRACT |
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INTRODUCTION |
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Recent studies indicate that gp120-associated glycans are modified among sequential isolates of HIV taken at different time points after infection in individual subjects (Wei et al., 2003). These modifications are associated with evolving resistance to antibody neutralization. These findings have given rise to the concept that gp120 remains resistant to antibody neutralization by use of a glycan shield, a protective coat of oligosaccharides that inhibits antibody binding to gp120 without blocking sites critical for binding to cellular receptors. A survey of sera from HIV-infected subjects showed a lack of effective neutralizing antibodies directed against carbohydrate epitopes on gp120 (Wei et al., 2003
). One illustrative exception is a broadly neutralizing monoclonal antibody, 2G12, that recognizes a specific constellation of high mannose oligosaccharides on the protein (Sanders et al., 2002
). Of interest, the high mannose oligosaccharides recognized by 2G12 are clustered on the end of gp120 most distal from the viral envelope and adjacent to the cell-binding domain of the molecule. These glycans are, therefore, highly accessible to binding by soluble or cell surface lectins or other ligands.
Mannosylated oligosaccharides on gp120 also are involved in the binding of HIV to the DC-SIGN lectin or homologous C-type lectin, langerin, expressed on the surface of dendritic cells and Langerhan's cells, respectively (Hong et al., 2002; Lue et al., 2002
; Turville et al., 2003
). Dendritic cell lectins appear to play an important role during initial infection with HIV. This receptor allows immature dendritic cells to bind HIV in mucosal locations (e.g. the vaginal mucosa) such that these cells then transmit the virus in viable form to lymphoid rich areas where T cells be infected (Turville et al., 2002
). Mannosylated glycans also mediate uptake of the virus by macrophages via the macrophage mannose receptor that also allows transmission of the infection to T cells (Nguyen & Hildreth, 2003
).
High mannose oligosaccharides on gp120 also represent a potential target for inhibition by antiviral agents, like the high mannose oligosaccharide-binding agent cyanovirin (Hong et al., 2002). Furthermore, mannose-binding lectin (MBL), a member of the collectin family of innate immune proteins, appears to contribute to host defence against HIV through a mechanism that involves binding to high mannose oligosaccharides on gp120 (Ezekowitz et al., 1989
; van de Wetering et al., 2004
). A recent study also demonstrated that MBL can inhibit DC-SIGN-mediated transfer of infectious HIV from dendritic cells to T cells (Spear et al., 2003
). Subjects having low blood levels of MBL due to polymorphic variations in the coding or promoter sequences of the protein have been found to have increased susceptibility to HIV infection in casecontrol studies (Boniotto et al., 2000
; Garred et al., 1997
; Pastinen et al., 1998
). Variant forms of MBL have also been associated with vertical transmission of HIV (Boniotto et al., 2000
). Whether low levels of MBL are associated with higher rates of disease progression or mortality after infection is controversial; some studies find an association (Garred et al., 1997
) and others do not (McBride et al., 1998
).
MBL binds to primary and highly passaged isolates of HIV via mannosylated carbohydrates on gp120 (Ezekowitz et al., 1989; Hart et al., 2003
; Saifuddin et al., 2000
). MBL neutralizes HIV in vitro, although the concentrations of MBL needed for neutralization are high (e.g. 2050 µg ml1) (Ezekowitz et al., 1989
; Hart et al., 2003
). Removal of sialic acid from the viral surface not only increased infectivity of simian immunodeficiency virus (SIV) (Means & Desrosiers, 2000
), but also increased susceptibility of HIV to neutralization by MBL (Hart et al., 2003
). Removal of terminal sialic acids from complex oligosaccharides may facilitate viral binding by reducing negative charge, and/or increasing accessibility of high mannose or hybrid oligosaccharides.
Glycosylation of gp120 appears, therefore, to play a pivotal role in mediating interactions of the virus with innate and adaptive components of the immune system. Although mannosylated glycans on HIV are highly conserved, and therefore presumably advantageous to the virus overall, they render the virus susceptible to inhibition by collectins and (apparently rare) glycan-specific antibodies. Recent studies have shown that another member of the collectin family, surfactant protein D (SP-D), is present not only in the lung, but also in various mucosal locations (Madsen et al., 2000) and in blood (Husby et al., 2002
), where it could interact with HIV. Importantly, SP-D, unlike MBL, is expressed in locations like the genito-urinary tract, oral cavity and gastrointestinal tract (Madsen et al., 2000
), where it could impede transmission of HIV. Furthermore, alveolar macrophages are an important site of HIV replication in advanced HIV disease, and replication in the lung becomes particularly pronounced in the presence of opportunistic infection (e.g. tuberculosis) (Hoshino et al., 2002
; Nakata et al., 1997
). Hence, SP-D could have important interactions with HIV in the lung itself. SP-D has been shown to play an important role in innate defence against influenza virus and respiratory syncitial virus infection (Crouch et al., 2000
; Hickling et al., 1999
; LeVine et al., 2001
). Polymorphisms of SP-D exist and affect susceptibility to some infections (Floros et al., 2000
; Lahti et al., 2002
). Recent studies have shown that serum levels and the extent of multimerization of SP-D vary depending on SP-D genotype as well (Husby et al., 2002
; Leth-Larsen et al., 2005
). In this study, we demonstrate that SP-D binds to gp120 and inhibits virus replication in culture with greater potency than MBL. The mechanism of this enhanced inhibition is also elucidated.
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METHODS |
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HIV envelope proteins.
The HIV envelope protein preparations were provided by the NIH AIDS research and reference reagent programme (www.aidsreagent.org). Three purified gp120 preparations were used: HIVBAL gp120 recombinant (called HIVBAL hereafter), HIV-1SF2162 gp120 (called HIVSF2 hereafter), and a nonglycosylated from of HIV-1SF2 gp120 (called HIVSF2deglyc hereafter). The HIVSF2deglyc preparation was also obtained from Chiron Corporation (Emeryville, CA, USA) as a gift after it was no longer provided by the NIH AIDS research and reference reagent programme. HIVBAL is a recombinant protein produced in HEK293 cells; it was purified by immunoaffinity chromatography and was derived from a macrophage-tropic viral strain. HIVSF2 was prepared in CHO cells and was also derived from a macrophage-tropic strain of HIV. The endotoxin level of this protein is 26·7 U endotoxin ml1 and the protein was diluted 100-fold for use in ELISA (hence giving a 0·267 U endotoxin ml1 working dilution). HIVBAL and HIVSF2 were both produced in mammalian cells, and hence have mammalian N-linked glycosylation. HIVSF2nonglyc is a nonglycosylated form of HIVSF2 produced in the yeast strain 2150; it elicits neutralizing antibodies in animals effective against HIVSF2 (Haigwood et al., 1992).
Glycan blotting of the gp120 preparations was carried out using the DIG-glycan differentiation kit (Roche Diagnostics), according to the manufacturer's specifications. In brief, the gp120 preparations were subjected to SDS-PAGE under reducing conditions and transferred to PVDF membranes. A positive control (carboxypeptidase Y, 63 kDa) was included. Presence of high mannose sugars was detected with the Galanthus nivalis agglutinin (GNA) coupled to digoxigenin.
Virus preparations.
HIVLAI strain was used in the infectivity experiments. The virus preparation was propagated in stimulated peripheral blood mononuclear cells from an HIV negative donor, and stored at a concentration of 105 particles ml1 at 80 °C until use. Influenza A virus (IAV) (Philippines 82/H3N2 strain) was grown in chicken eggs and purified by sucrose density gradients as described previously (Hartshorn et al., 1988).
Collectin preparations.
Recombinant human SP-D (RhSP-D) and SP-D/MBLneck+CRD chimera were produced in CHO-K1 cells as previously described (Hartshorn et al., 1996a). The SP-D/MBLneck+CRD chimera was prepared by recombinant splicing of the neck domain and carbohydrate recognition domain (CRD) of MBL onto the N-terminus and collagen domain of human SP-D (White et al., 2000
). The chimera forms trimers, dodecamers and high molecular mass multimers in a manner similar to RhSP-D (White et al., 2001
). The chimera has a higher affinity for mannose than wild-type RhSP-D, and has increased ability to bind to, aggregate and neutralize IAV compared to either wild-type SP-D or MBL. For most experiments, the dodecameric RhSP-D and SP-D/MBLneck+CRD were used. However, to assess the role of collectin multimerization in the binding to HIV gp120 trimers, dodecamers and higher molecular mass multimers of SP-D/MBLneck+CRD were compared. The mode of purification of these fractions of RhSP-D or SP-D/MBLneck+CRD has been previously described in detail (Hartshorn et al., 1996a
; White et al., 2000
, 2001
). Recombinant human MBL (RhMBL) was produced in murine Sp2 cells (Hartshorn et al., 1993
; Super et al., 1992
). RhMBL was kindly provided by Dr Kazue Takahashi and Dr R. A. B. Ezekowitz (Department of Pediatrics, Harvard Medical School, Boston, MA, USA). This RhMBL was the more common allelic variant (termed MBPG), and the preparation is composed predominantly of multimers containing five or six trimers (i.e. octadecamers) in association (Super et al., 1992
).
Native human SP-D and SP-A were also tested. Native human SP-D was isolated from amniotic fluid (Leth-Larsen et al., 2005; Strong & Kishore, 1998
) using maltose affinity chromatography. Gel filtration chromatography was used to separate trimeric and more highly multimerized (mainly dodecameric) forms (Hartshorn et al., 1996a
).
The collectin preparations were tested for endotoxin contamination using a quantitative endotoxin assay (Limulus amebocyte lysate; Cambrex). The final concentrations of endotoxin in samples containing the highest concentrations of collectins were 20100 pg ml1 (or 612 U endotoxin ml1 using an internal assay standard).
Assessment of the binding of collectins to HIV envelope proteins.
The binding of collectins to envelope proteins was measured by ELISA. The envelope proteins were diluted to 20 µg ml1 and allowed to adhere to ELISA plates overnight at 4 °C. The plates were then centrifuged at 2500 r.p.m. and fixed by brief incubation with 95 % ethanol, followed by 10 min incubation with methanol. The plates were then dried for 30 min. at 37 °C and incubated with PBS containing 2·5 % fatty-acid-free BSA (Sigma) for 2 h to block nonspecific binding. After washing, the plates were incubated with various concentrations of biotinylated collectins. Biotinylation of recombinant collectins has been previously described (Hartshorn et al., 2000). Background binding was determined using wells coated with BSA only (see Fig. 3
). Wells coated with IAV were used as a positive control. The binding of the HIVSF2deglyc preparation to ELISA plates was confirmed by a separate ELISA using an goat polyclonal antibody raised against the protein [provided by the NIH AIDS research and reference reagent programme (www.aidsreagent.org)]. Maximal binding was seen at 2 µg ml1, and a concentration of 20 µg ml1 was used in the assay to assure maximal coating.
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Assessment of the effect of collectins on replication of HIV.
The ability of collectins to inhibit HIV replication was tested using U937 cells (ATCC) (Callahan et al., 2003; Hammer et al., 1986
; Hartshorn et al., 1987
; Zhang et al., 1995
). The cells were cultured in 96-well plates to minimize the amounts of collectins needed. The plates were seeded with 3x105 cells in 200 µl RPMI containing 20 % fetal bovine serum. The cells were then inoculated with HIV at an m.o.i. of 0·07. Prior to inoculation the virus was pre-incubated with various concentrations of collectins (or control buffer only) for 30 min at 37 °C. The cells were then maintained in culture in the presence of the same concentration of collectins. Every 34 days, 100 µl cell suspension was removed and cell-free supernatants were frozen for use in an HIV-1 p24 antigen assay by ELISA. Fresh media was added with collectin concentrations being maintained by the addition of sufficient amounts of the proteins along with the media.
The level of virus replication was assayed by measurement of p24 antigen levels in the supernatant using a p24 antigen ELISA kit obtained from Perkin Elmer Life Sciences, following the manufacturer's instructions. Briefly, 100 µl cell-free supernatants from HIV infected U937 cells were added to assay wells that were coated with mAb specific for the p24 protein of HIV-1. For each assay negative and positive controls were included, and standard curves were obtained through the addition of known amounts of purified p24 antigen. These controls showed consistent results through all the assays, and were within the expected range (according to the manufacturer's instructions). The supernatants and controls were incubated for 2 h at 37 °C. After washing, the plates were incubated for 1 h at 37 °C with biotinylated polyclonal antibodies directed against HIV-1 p24 protein. Bound antibody was detected by the addition of streptavidin-HRP and OPD substrate solution.
Statistics.
Statistical comparisons were made using Student's paired t-test and ANOVA using the Statmost program.
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RESULTS |
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SP-A does not bind to gp120 of HIV
The mechanism of binding of SP-A to IAV differs from that of SP-D, and does not involve recognition of IAV-associated carbohydrates by the lectin activity of SP-A. Instead, SP-A binds to IAV via attachment of the viral haemagglutinin to sialic acids on SP-A (Benne et al., 1995; van Eijk et al., 2003
, 2004
). Despite strong binding to IAV, we found no measurable binding of SP-A to gp120 of HIVBAL (mean OD450 for the binding of 2·5 µg SP-A ml1 to gp120 was 0·07±0·01 as compared to 0·86±0·26 for the binding to IAV, n=4, P<0·04, background binding to BSA subtracted prior to analysis).
Binding of SP-D to gp120 exceeds the binding of MBL: the role of the CRD
As shown in Fig. 4(a), RhMBL bound to HIVBAL to an extent comparable to its binding to IAV. The binding to HIVBAL was significantly greater than the binding to HIVSF2, which in turn exceeded the binding to HIVSF2deglyc, consistent with the previously demonstrated binding of MBL to HIV (or IAV) (Hartshorn et al., 1993
) via its CRD. Note again that the relatively greater binding of MBL to HIVBAL, compared to the binding to HIVSF2, could reflect a lower amount of high mannose oligosaccharides on the latter preparation. The binding of MBL was compared to the binding of SP-D using biotinylated preparations of the collectins (Fig. 4b, c, d
). A comparable extent of biotinylation was confirmed by the similar binding of streptavidin-HRP to equal amounts of the proteins coated directly on ELISA plates (data not shown). SP-D bound significantly more than MBL to HIVBAL or HIVSF2 in these assays. Similar results have been obtained with IAV in prior studies (White et al., 2000
).
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The binding of the recombinant collectins was also tested by an alternative method in which the bound collectins were detected by specific mAbs (Fig. 5). The mAb directed against the CRD of MBL and the mAb directed against SP-D resulted in similar OD450 values when reacted with equal concentrations of various fractions of SP-D/MBLneck+CRD (for the MBL antibody) and RhSP-D dodecamers (for the SP-D antibody). When testing the binding of the collectins using these antibodies, dodecamers of SP-D/MBLneck+CRD again bound more strongly to gp120 of HIVBAL as compared to dodecamers of SP-D (Fig. 5
). Higher molecular mass multimers (that contained as many as 32 trimeric CRD heads) and trimers of SP-D/MBLneck+CRD were also tested. The binding of the higher molecular mass multimers to HIV gp120 was not greater than the binding of dodecamers. However, the trimeric fraction of SP-D/MBLneck+CRD bound markedly less than multimers or dodecamers. Thus, the degree of multimerization was a critical determinant of the increased binding activity of SP-D/MBLneck+CRD.
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SP-D inhibits infectivity of HIV at significantly lower concentrations than MBL
To determine if the increased ability of SP-D to bind to HIV gp120 is associated with a greater ability to inhibit infectivity of the virus, we utilized a model of infection of the highly susceptible undifferentiated U937 cells. Results of an HIV neutralization experiments are shown in Fig. 6. A replicate experiment is shown in Table 1
. SP-D caused significant inhibition of HIV replication at concentrations of
2 µg ml1 in both experiments at 3 or 6 days after infection. Although inhibition by SP-D was only partial in this model at the concentrations tested, the results overall were similar to the binding results regarding the comparative activity of SP-D, MBL and SP-D/MBLneck+CRD.
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DISCUSSION |
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For viral neutralization assays, we chose to test concentrations of SP-D similar to those found in blood or unconcentrated BAL fluids. At these concentrations inhibition of infectivity of HIV was only partial, whereas similar concentrations fully inhibit infectivity of IAV (Hartshorn et al., 2000). The reasons for this discrepancy are unclear, although it is possible that SP-D-bound HIV can still enter and infect U937 cells to a reduced extent. The rationale for choosing U937 cells was to avoid known effects of SP-D on activation and proliferation of peripheral blood lymphocytes, which could be confounding (Borron et al., 1998
). In addition, the most likely site of HIV replication in the lung or other mucosal sites would be macrophages so that macrophage like cells should be more relevant for our studies. It will, of course, also be of great interest to study the effects of SP-D on HIV infection of lymphocytic cells. In any case our current results show that SP-D can exert suppressive effects on HIV replication in macrophage-like cells. This may be significant in vivo because alveolar macrophages may be an important reservoir of infection in advanced HIV disease (Hoshino et al., 2002
). It will also be important to determine if SP-D can inhibit replication of primary isolates of HIV and macrophage-tropic strains since results may differ from those obtained with HIVLAI (Saifuddin et al., 2000
).
The mechanism of binding of SP-D to HIV gp120 (i.e. calcium dependent attachment to N-linked sugars) resembles its binding to various other microbial ligands, including IAV (for which SP-D plays a key role in host defence; Hartshorn et al., 1994; Hawgood et al., 2004
; LeVine et al., 2001
; Reading et al., 1997
). Notably, SP-D shows a higher apparent affinity for HIV gp120 than MBL. Using the SP-D/MBLneck+CRD chimera we demonstrated that the greater binding activity of SP-D is not the result of differences in the binding affinity of the CRD domain of SP-D, since the SP-D/MBLneck+CRD chimera also bound more strongly than MBL. Very similar results were obtained in studies of influenza viruses (White et al., 2000
).
The greater binding activity of SP-D compared to MBL must then result from differences in the N-terminal and collagen domains of the molecule, or associated differences in the number or spatial distribution of CRDs. The greatly reduced binding of the trimeric form of SP-D/MBLneck+CRD indicates that cooperative binding interactions between trimeric CRD globular domains in dodecameric molecules are necessary for the increased binding activity of SP-D/MBLneck+CRD. Presumably the N-terminal and collagen domains of SP-D allow greater cooperativity of binding between globular CRD trimeric heads on an individual molecule than those of MBL. Studies with influenza virus and bacteria indicate that the N-terminal and collagen domains of SP-D confer much greater viral and bacterial aggregating activity than those of MBL (Hartshorn et al., 2002; White et al., 2000
, 2001
). In these studies the enhanced viral-binding and -aggregating activity of SP-D was also dependent on higher order multimerization of the molecule. Trimeric forms of SP-D had reduced binding activity and lacked viral aggregating activity in prior studies (Brown-Augsburger et al., 1996
; White et al., 2000
, 2001
). The finding in this paper of the reduced binding to gp120 by predominantly trimeric low molecular mass native SP-D is, therefore, consistent with prior results.
We used two different methodologies to assess relative binding of the collectins (i.e. biotinylation of the collectins, and detection with anti-SP-D or anti-MBL antibodies) with similar results. Furthermore, the relative binding paralleled findings with influenza virus. Hence, the overall conclusion that SP-D and SP-D/MBLneck+CRD have stronger binding to HIV gp120 than MBL seems well supported. The relative binding activity of these collectins also correlated with their ability to inhibit replication of HIV.
Previous studies have demonstrated that MBL inhibits HIV replication in culture, although the concentrations needed to achieve neutralization were relatively high (e.g. partial inhibition at 2030 µg ml1) (Ezekowitz et al., 1989; Hart et al., 2003
). Hence, the failure to demonstrate inhibition of HIV replication by MBL at the doses used in our study is consistent with other observations. The ability of MBL to fix complement on HIV-infected cells could be important to its in vivo activity (Haurum et al., 1993
). Also, the collectins could promote uptake of viruses by phagocytic cells, which could be important in vivo aside from neutralizing activity (Hartshorn et al., 1996b
, 1997
, 1998
; Ying et al., 2004
). Recent studies have demonstrated that various components of the innate immune system have important interactions with the adaptive immune system (Borron et al., 2002
; Brinker et al., 2001
). Furthermore, SP-D has important roles in regulating oxidant and phospholipid metabolism in the lung, and the clearance of apoptotic cells (Clark et al., 2002
; Wert et al., 2000
). It is possible that the ability of SP-D to bind to HIV could affect the presentation of HIV antigens to dendritic cells, or that its other immunoregulatory and homeostatic activities could affect adaptive immune responses in the context of HIV infection. Future studies are needed to address whether SP-D modulates phagocyte uptake of HIV. Such an effect could contribute to containment of HIV in vivo or even facilitate infection (e.g. as in the case of DC-Sign; Spear et al., 2003
).
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ACKNOWLEDGEMENTS |
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REFERENCES |
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Boniotto, M., Crovella, S., Pirulli, D. & 7 other authors (2000). Polymorphisms in the MBL2 promoter correlated with risk of HIV-1 vertical transmission and AIDS progression. Genes Immun 1, 346348.[CrossRef][Medline]
Borron, P., Crouch, E., Lewis, J., Wright, J., Possmayer, F. & Fraher, L. (1998). Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production. J Immunol 161, 45994603.
Borron, P. J., Mostaghel, E. A., Doyle, C., Walsh, E. S., McHeyzer-Williams, M. G. & Wright, J. R. (2002). Pulmonary surfactant proteins A and D directly suppress CD3+/CD4+ cell function: evidence for two shared mechanisms. J Immunol 169, 58445850.
Brinker, K. G., Martin, E., Borron, P., Mostaghel, E., Doyle, C., Harding, C. V. & Wright, J. R. (2001). Surfactant protein D enhances bacterial antigen presentation by bone-marrow derived dendritic cells. Am J Physiol 281, L1453L1463.
Brown-Augsburger, P., Hartshorn, K., Chang, D., Rust, K., Fliszar, C., Welgus, H. & Crouch, E. (1996). Site directed mutagenesis of Cys15 and Cys20 of pulmonary surfactant protein D: expression of a trimeric protein with altered anti-viral properties. J Biol Chem 271, 1372413730.
Callahan, M. K., Popernack, P. M., Tsutsui, S., Truong, L., Schlegel, R. A. & Henderson, A. J. (2003). Phosphatidylserine on HIV envelope is a cofactor for infection of monocytic cells. J Immunol 170, 48404845.
Clark, H., Palaniyar, N., Strong, P., Edmondson, J., Hawgood, S. & Reid, K. (2002). Surfactant protein D reduces alveolar macrophage apoptosis in vivo. J Immunol 169, 28922899.
Crouch, E., Hartshorn, K. & Ofek, I. (2000). Collectins and pulmonary innate immunity. Immunol Rev 173, 5265.[CrossRef][Medline]
Ezekowitz, R. A. B., Kuhlman, M., Groopman, J. & Byrn, R. A. (1989). A human serum mannose-binding protein inhibits in vitro infection by the human immunodeficiency virus. J Exp Med 169, 185196.
Floros, J., Lin, H., Garcia, A. & 7 other authors (2000). Surfactant protein marker alleles identify a subgroup of tuberculosis patients in a Mexican population. J Infect Dis 182, 14731478.[CrossRef][Medline]
Garred, P., Madsen, H., Balslev, U., Pedersen, C., Gerstoft, J. & Svegaard, A. (1997). Susceptibility to HIV infection and progression of AIDS in relation to variant alleles of mannose-binding lectin. Lancet 349, 236240.[CrossRef][Medline]
Haigwood, N. L., Nara, P. L., Brooks, E. & 7 other authors (1992). Native but not denatured recombinant human immunodeficiency virus type 1 gp120 generates broad-spectrum neutralizing antibodies in baboons. J Virol 66, 172182.[Medline]
Hammer, S. M., Gillis, J. M., Groopman, J. E. & Rose, R. M. (1986). In vitro modification of human immunodeficiency virus infection by granulocytemacrophage colony-stimulating factor and interferon. Proc Natl Acad Sci U S A 83, 87348738.
Hart, M., Saifuddin, M. & Spear, G. (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., Neumeyer, D., Vogt, M. V., Schooley, R. T. & Hirsch, M. S. (1987). Activity of interferons alpha, beta, and gamma against human immunodeficiency virus in vitro. AIDS Res Hum Retroviruses 3, 125133.[Medline]
Hartshorn, K. L., Collamer, M., Auerbach, M., Myers, J. B., Pavlotsky, N. & Tauber, A. I. (1988). Effects of influenza A virus on human neutrophil calcium metabolism. J Immunol 141, 12951301.
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., Crouch, E. C., White, M. R., Eggleton, P., Tauber, A. I., Chang, D. & Sastry, K. (1994). Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. J Clin Invest 94, 311319.[Medline]
Hartshorn, K. L., Chang, D., Rust, K., White, M. R., Heuser, J. & Crouch, E. C. (1996a). Interactions of recombinant human pulmonary surfactant protein D and SP-D multimers with influenza A. Am J Physiol 271, L753L762.
Hartshorn, K. L., Reid, K. B. M., White, M. R., Jensenius, J. C., Morris, S. M., Tauber, A. I. & Crouch, E. (1996b). Neutrophil deactivation by influenza A viruses: mechanisms of protection after viral opsonization with collectins and hemagglutination-inhibiting antibodies. Blood 87, 34503461.
Hartshorn, K. L., White, M. R., Shepherd, V., Reid, K., Jensenius, J. C. & Crouch, E. C. (1997). Mechanisms of anti-influenza activity of pulmonary surfactant proteins A and D: comparison with other collectins. Am J Physiol 273, L11561166.
Hartshorn, K. L., Crouch, E., White, M. R., Colamussi, M. L., Kakkanatt, A., Tauber, B., Shepherd, V. & Sastry, K. N. (1998). Pulmonary surfactant proteins A and D enhance neutrophil uptake of bacteria. Am J Physiol 274, L958L969.
Hartshorn, K. L., White, M. R., Voelker, D. R., Coburn, J., Zaner, K. & Crouch, E. C. (2000). Mechanism of binding of surfactant surfactant protein D to influenza A viruses: importance of binding to haemagglutinin to antiviral activity. Biochem J 351, 449458.[CrossRef][Medline]
Hartshorn. , White, M. R. & Crouch, E. C. (2002). Contributions of the N- and C-terminal domains of surfactant protein D to the binding, aggregation, and phagocyte uptake of bacteria. Infect Immun 70, 61296139.
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]
Hawgood, S., Brown, C., Edmondson, J., Stumbaugh, A., Allen, L., Goerke, J., Clark, H. & Poulain, F. (2004). Pulmonary collectins modulate strain-specific influenza A virus infection and host responses. J Virol 78, 85658572.
Hickling, T. P., Bright, H., Wing, K., Gower, D., Martin, S. L., Sim, R. B. & Malhotra, R. (1999). A recombinant trimeric surfactant protein D carbohydrate recognition domain inhibits respiratory synctitial virus infection in vitro and in vivo. Eur J Immunol 29, 34783484.[CrossRef][Medline]
Hong, P. W.-P., Flummerfelt, K. B., de Parseval, A., Gurney, K., Elder, J. H. & Lee, B. (2002). Human immunodeficiency virus envelope (gp120) binding to DC-SIGN and primary dendritic cells is carbohydrate dependent but does not involve 2G12 or cyanovirin binding sites: implications for structural analysis of gp120-DC-SIGN binding. J Virol 76, 1285512865.
Hoshino, Y., Nakata, K., Hoshino, S., Honda, Y., Tse, D. B., Shioda, T., Rom, W. N. & Weiden, M. (2002). Maximal HIV-1 replication in alveolar macrophages during tuberculosis requires both lymphocyte contact and cytokines. J Exp Med 195, 495505.
Husby, S., Herskind, A., Jensenius, J. & Holmkov, U. (2002). Heritability estimates for the constitutional levels of the collectins, mannan-binding lectin and lung surfactant protein D. Immunology 106, 389394.[CrossRef][Medline]
Lahtl, M., Lofgren, J., Martilla, T., Renko, M., Klaavenuniemi, T., Haataja, R., Ramet, M. & Hallman, M. (2002). Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection. Pediatr Res 51, 696699.
Leonard, C., Spellman, M., Riddle, L., Harris, R., Thomas, J. & Gregory, T. (1990). Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem 265, 1037310382.
Leth-Larsen, R., Floridon, C., Nielsen, O. & Holmskov, U. (2004). Surfactant protein D in the female genital tract. Mol Hum Reprod 10, 149154.
Leth-Larsen, R., Garred, P., Jensenius, H. & 8 other authors (2005). A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. J Immunol 174, 15321538.
LeVine, A., Whitsett, J., Hartshorn, K. & Korfhagen, T. (2001). Surfactant protein D enhances clearance of influenza A virus from the lung in vivo. J Immunol 167, 58685873.
Lue, J., Hsu, M., Yang, D., Marx, P., Chen, Z. & Cheng-Mayer, C. (2002). Addition of a single gp120 glycan confers increased binding to dendritic cell-specific ICAM-3-grabbing nonintegrin and neutralization escape to human immunodeficiency virus type 1. J Virol 76, 1029910306.
Madsen, J., Kliem, A., Tornoe, I., Skjolt, K., Koch, C. & Holmskov, U. (2000). Localization of lung surfactant protein D on mucosal surfaces in human tissues. J Immunol 164, 58665870.
McBride, M., Fischer, P., Sumiya, M., McClure, M., Turner, M., Skinner, C., Weber, J. & Summerfield, J. (1998). Mannose-binding protein in HIV-seropositive patients does not contribute to disease progression or bacterial infections. Int J STD AIDS 9, 683688.[CrossRef][Medline]
Means, R. & Desrosiers, R. (2000). Resistance of native, oligomeric envelope on simian immunodeficiency virus to digestion by glycosidases. J Virol 74, 1118111190.
Nakata, K., Rom, W. N., Honda, Y., Condos, R., Kanegasaki, S., Cao, Y. & Weiden, M. (1997). Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication in the lung. Am J Respir Crit Care Med 155, 9961003.[Abstract]
Nguyen, D. & Hildreth, J. (2003). Involvement of macrophage mannose receptor in the binding and transmission of HIV by macrophages. Eur J Immunol 33, 483493.[CrossRef][Medline]
Pastinen, T., Liitsola, K., Niini, P., Salminen, M. & Syvanen, A. (1998). Contribution of CCR5 and MBL genes to susceptibility to HIV type 1 infection in the Finnish population. AIDS Res Hum Retroviruses 14, 695698.[Medline]
Reading, P. C., Morey, L. S., Crouch, E. C. & Anders, E. (1997). Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice. J Virol 71, 82048212.[Abstract]
Saifuddin, M., Hart, M., Gewurz, H., Zhang, Y. & Spear, G. (2000). Interaction of mannose-binding lectin with primary isolates of human immunodeficiency virus 1. J Gen Virol 81, 949955.
Sanders, R., Venturi, M., Schiffner, L., Kalyanaraman, R., Katinger, H., Lloyd, K., Kwong, P. & Moore, J. (2002). The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J Virol 76, 72937305.
Spear, G., Zariffard, M., Xin, J. & Saifuddin, M. (2003). Inhibition of DC-sign mediated trans infection of T cells by mannose-binding lectin. Immunology 110, 8083.[CrossRef][Medline]
Strong, P. & Kishore, U. (1998). A novel method of purifying lung surfactant proteins A and D from the lung lavage of alveolar proteinosis patients from pooled amniotic fluid. J Immunol Methods 220, 139149.[CrossRef][Medline]
Super, M., Gillis, S., Foley, S., Sastry, K., Schweinle, J. E., Silverman, V. J. & Ezekowitz, R. A. B. (1992). Distinct and overlapping functions of allelic forms of human mannose binding protein. Nat Genet 2, 5055.[CrossRef][Medline]
Turville, S., Cameron, P., Handley, A., Lin, G., Pohlmann, S., Doms, R. & Cunningham, A. (2002). Diversity of receptors binding HIV on dendritic cell subsets. Nat Immunol 3, 975983.[CrossRef][Medline]
Turville, S., Wilkinson, J., Cameron, P., Dable, J. & Cunningham, A. L. (2003). The role of dendritic cell C-type lectin receptors in HIV pathogenesis. J Leukoc Biol 74, 710718.
van de Wetering, J. K., van Golde, L. M. & Batenburg, J. J. (2004). Collectins: players of the innate immune system. Eur J Biochem 271, 12291249.
van Eijk, M., White, M. R., Crouch, E. C., Batenburg, J. J., Vaandrager, A. B., van Golde, L. M., Haagsman, H. P. & Hartshorn, K. L. (2003). Porcine pulmonary collectins show distinct interactions with influenza A viruses: role of the N-linked oligosaccharides in the carbohydrate recognition domain. J Immunol 171, 14311440.
van Eijk, M., White, M. R., Batenburg, J. J., Vaandrager, A. B., van Golde, L. M., Haagsman, H. P. & Hartshorn, K. L. (2004). Interactions of influenza A virus with sialic acids present on porcine surfactant protein D. Am J Respir Cell Mol Biol 30, 871879.
Wei, X., Decker, J., Wang, S. & 12 other authors (2003). Antibody neutralization and escape by HIV-1. Nature 422, 307312.[CrossRef][Medline]
Wert, S., Yoshida, M., LeVine, A., Ikegami, M., Jones, T., Ross, G., Fisher, J., Korfhagen, T. & Whitsett, J. (2000). Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice. Proc Natl Acad Sci U S A 97, 59725977.
White, M., Crouch, E., Chang, D., Sastry, K., Guo, N., Engelich, G., Takahashi, K., Ezekowitz, R. & Hartshorn, K. (2000). Enhanced antiviral and opsonic activity of a human mannose binding lectin and surfactant protein D fusion protein. J Immunol 165, 21082155.
White, M., Crouch, E., Chang, D. & Hartshorn, K. (2001). Increased antiviral and opsonic activity of a highly multimerized collectin chimera. Biochem Biophys Res Commun 286, 206213.[CrossRef][Medline]
Wright, J. (1997). Immunomodulatory functions of surfactant. Physiol Rev 77, 931962.
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]
Zhang, Y., Nakata, K., Weiden, M. & Rom, W. N. (1995). Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication by transcriptional activation at the long terminal repeat. J Clin Invest 95, 23242331.[Medline]
Received 17 November 2004;
accepted 12 August 2005.
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