Heparin-binding domain of human fibronectin binds HIV-1 gp120/160 and reduces virus infectivity

Bozzini, Silvia; Falcone, Valeria; Conaldi, Pier Giulio; Visai, Livia; Biancone, Luigi; Dolei, Antonina; Toniolo, Antonio; Speziale, Pietro

doi:10.1002/(sici)1096-9071(199801)54:1<44::aid-jmv7>3.0.co;2-p

Cited by 27 publications

(26 citation statements)

References 43 publications

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“…This agrees with our previous finding that III1-C fragment itself can increase HIV infection. This finding may be important during inflammation or wound healing where proteases are released that generate proteolytic fragments with potential biological activities (30). Proteolysis of extracellular matrix releases cryptic activities that can signal differently than the intact protein (31).…”

Section: Discussionmentioning

confidence: 99%

Matrix Fibronectin Increases HIV Stability and Infectivity

Greco

Pal

Pasqualini

et al. 2002

The Journal of Immunology

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HIV particles are detected extracellularly in lymphoid tissues, a major reservoir of the virus. We previously reported that a polymerized form of fibronectin (FN), superfibronectin (sFN), as well as a fragment of FN, III1-C, enhanced infection of primary CD4+ T cells by HIV-1IIIB. We now show that sFN enhances infection of primary CD4+ T cells by both R5 and X4 strains of HIV-1. Using HIV pseudotyped with different envelope glycoproteins (gp120) and HOS cells transfected with various chemokine receptors alone or in combination with the CD4 molecule, we show that sFN-mediated enhancement requires the CD4 receptor and does not alter the specificity of gp120 for different chemokine receptors. Because the III1-C fragment also resulted in enhancement, we asked whether proteolysis of FN generated fragments capable of enhancing HIV infection. We found that progressive proteolysis of FN by chymotrypsin correlates with an enhancement of HIV infection in both primary CD4+ T cells and the IG5 reporter cell line. Furthermore, incubation of HIV with sFN significantly prolonged infectivity at 37°C compared with dimeric FN or BSA. In conclusion, these results indicate that polymerized (matrix) or degraded (inflammation-associated), but not dimeric (plasma), FN are capable of enhancing infection by HIV-1, independent of the coreceptor specificity of the strains. Moreover, virions bound to matrix FN maintain infectivity for longer periods of time than do virions in suspension. This study suggests that matrix proteins and their conformational status may play a role in the pathogenesis of HIV.

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Section: Discussionmentioning

confidence: 99%

Matrix Fibronectin Increases HIV Stability and Infectivity

Greco

Pal

Pasqualini

et al. 2002

The Journal of Immunology

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“…The 220-to 250-kDa monomers are bound together with two disulfide bonds near the carboxyl terminus. Fibronectin has a pI of 5.6 to 6.3, with peak activity at 6.1, but is reported to suffer rapid loss of activity at temperatures over 60 to 65°C (2). In contrast, the native fibronectin complex isolated here had a molecular size of ϳ320 kDa, while the monomer was 220 kDa with a pI of 4.9.…”

Section: Discussionmentioning

confidence: 99%

Isolation of a Bovine Plasma Fibronectin-Containing Complex Which Inhibits the Expression of Bovine Leukemia Virus p24

Heuvel

Jefferson

Jacobs

2005

J Virol

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Bovine leukemia virus (BLV) is a deltaretrovirus that infects cattle worldwide. In agriculturally intensive regions, approximately 30% of dairy cows are BLV infected. Like the human T-cell leukemia virus (HTLV), there is a lengthy period of viral quiescence after initial infection with BLV. Unlike HTLV, BLV resides predominantly in B cells. Lymphoma is observed in less than 10% of BLV-infected adult cattle. Although viremia is undetectable in vivo, BLV-infected peripheral blood mononuclear cells readily become productive when cultured in vitro. Productivity is markedly diminished when cultures are supplemented with bovine plasma. This inhibitory activity of bovine plasma has been attributed to the "plasma blocking factor" (PBF). Here, we describe the purification of a PBF whose activity was resistant to heating to 65°C for 10 min and was attributable to a fibronectin-containing complex of approximately 320 kDa under nonreducing conditions. By use of two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionizationtime of flight (mass spectrometry), a protein with a size of 220 kDa and a pI of 5.4 was identified as a member of the fibronectin group of molecules. Both the purified protein and the commercially available bovine fibronectin inhibited BLV production in naturally infected peripheral blood mononuclear cells, although the fibronectin was less biologically active.

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“…Binding of HIV to FN is thought to be mediated by the envelope protein of HIV (38). We examined whether this was also true for binding of HIV to sFN or the III 1 -C peptide.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the binding of HIV to III 1 -C appears to involve the CD4 binding domain of gp120 and not the V3 loop. Others have shown specific binding of the HIV-1 IIIB envelope protein (gp160) to the heparin binding domain located in the FN carboxyl terminal (38). We speculate that the heparin cell binding domain that contains the III 1 -C region mediates binding of HIV to sFN.…”

Section: Discussionmentioning

confidence: 99%

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Superfibronectin, a Multimeric Form of Fibronectin, Increases HIV Infection of Primary CD4+ T Lymphocytes

Tellier

Greco

Klotman

et al. 2000

The Journal of Immunology

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The ability of viruses and bacteria to interact with the extracellular matrix plays an important role in their infectivity and pathogenicity. Fibronectin is a major component of the extracellular matrix in lymph node tissue, the main site of HIV deposition and replication during the chronic phase of infection. Therefore, we asked whether matrix fibronectin (FN) could affect the ability of HIV to infect lymphocytes. To study the role of matrix FN on HIV infection, we used superfibronectin (sFN), a multimeric form of FN that closely resembles in vivo matrix FN. In this study we show that HIV-1IIIB efficiently binds to multimeric fibronectin (sFN) and that HIV infection of primary CD4+ lymphocytes is enhanced by >1 order of magnitude in the presence of sFN. This increase appears to be due to increased adhesion of viral particles to the cell surface in the presence of sFN, followed by internalization of virus. Enzymatic removal of cell surface proteoglycans inhibited the adhesion of HIV-1IIIB/sFN complexes to lymphocytes. In contrast, Abs to integrins had no effect on binding of HIV-1IIIB/sFN complexes to lymphocytes. The III1-C peptide alone also bound HIV-1IIIB efficiently and enhanced HIV infection, although not as effectively as sFN. HIV-1IIIB gp120 envelope protein binds to the III1-C region of sFN and may be important in the interaction of virus with matrix FN. We conclude that HIV-1IIIB specifically interacts with the III1-C region within matrix FN, and that this interaction may play a role in facilitating HIV infection in vivo, particularly in lymph node tissue.

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Heparin-binding domain of human fibronectin binds HIV-1 gp120/160 and reduces virus infectivity

Cited by 27 publications

References 43 publications

Matrix Fibronectin Increases HIV Stability and Infectivity

Matrix Fibronectin Increases HIV Stability and Infectivity

Isolation of a Bovine Plasma Fibronectin-Containing Complex Which Inhibits the Expression of Bovine Leukemia Virus p24

Superfibronectin, a Multimeric Form of Fibronectin, Increases HIV Infection of Primary CD4+ T Lymphocytes

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