Infection of colonic epithelial cell lines by type 1 human immunodeficiency virus is associated with cell surface expression of galactosylceramide, a potential alternative gp120 receptor.

Fantini, Jacques; Cook, David G.; Nathanson, Neal; Spitalnik, Steven L.; González‐Scarano, Francisco

doi:10.1073/pnas.90.7.2700

Cited by 235 publications

(158 citation statements)

References 33 publications

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“…The rationale for this strategy was based on previous observations suggesting that the GalCer receptor, putatively used by HIV-1 to infect neural cells (16,17) and colon cells (18,19), was recognized by the V3 domain of gp120: (i) anti-V3 antibodies block gp120 binding to GalCer (26); (ii) these antibodies inhibit HIV-1 infection of CD4 Ϫ /GalCer ϩ human colon epithelial HT-29 cells (15,26); (iii) synthetic multimeric peptide constructs of the V3 consensus sequence (GPGRAF) bind to GalCer and prevent HIV-1 entry into HT-29 cells (24); (iv) the V3 loop is a common genetic determinant controlling HIV-1 tropism for neural SKNMC cells (17,28) and HT-29 cells (29), as demonstrated by using chimeric proviral clones. Although these data strongly suggested the involvement of the V3 loop in GalCer recognition, direct evidences for a physical interaction between GalCer and the V3 loop of gp120 were lacking.…”

Section: Discussionmentioning

confidence: 99%

“…An antigen capture assay (DuPont, Les Ulis, France) was used for p24 determinations. The viruses used in these experiments were the prototype HIV-1(LAI) or the african HIV-1(NDK) isolates, as described previously (18,19,22,24).…”

Section: Materials-spc3 Ie (Gpgraf)mentioning

confidence: 99%

“…of 0.1 TCID 50 per cell) was preincubated with various concentrations of CA52(n15) and then exposed to exponentially growing HT-29 cells cultures in six-well plates. After 2 h of infection, the cells were treated with trypsin to inactivate residual inoculum (19), and the level of infection was analyzed 7 days later by measuring the production of HIV-1 p24 antigen in the cell-free culture supernatant. The results in Fig.…”

Section: Anti-hiv-1 Activity Of Ca52(n15)-mentioning

confidence: 99%

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Synthetic Soluble Analogs of Galactosylceramide (GalCer) Bind to the V3 Domain of HIV-1 gp120 and Inhibit HIV-1-induced Fusion and Entry

Fantini¹,

Hammache²,

Delézay³

et al. 1997

Journal of Biological Chemistry

119

107

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Galactosylceramide (GalCer) is an alternative receptor allowing human immunodeficiency virus (HIV)-1 entry into CD4-negative cells of neural and colonic origin.Several lines of evidence suggest that this glycosphingolipid recognizes the V3 region of HIV-1 surface envelope glycoprotein gp120. Since the V3 loop plays a key role in the fusion process driven by HIV-1, we decided to synthesize soluble analogs of GalCer with the aim to develop a new class of anti-HIV-1 agents that could neutralize HIV-1 infection through masking of the V3 loop. We describe a short route, in three steps, for the synthesis of soluble analogs of GalCer, using unprotected lactose as the starting sugar. The analogs were prescreened in an assay based on the interaction between a V3 loopderived synthetic peptide and [ 3 H]suramin, a polysulfonyl compound displaying high affinity for the V3 loop. One of the soluble analogs, i.e. CA52(n15), strongly inhibited the binding of [ 3 H]suramin to the V3 peptide, with an IC 50 of 1.2 M. This molecule was also able to inhibit [ 3 H]suramin binding to recombinant gp120 with similar activity. Using a competition enzyme-linked immunosorbent assay with highly specific anti-gp120 monoclonal antibodies, the region recognized by CA52(n15) could be mapped to amino acids 318 -323, which corresponds to the highly conserved consensus motif GPGRAF. Interestingly, the region recognized by suramin, i.e. IQRGP-R-F, was partially overlapping this motif. CA52(n15) was able to inhibit HIV-1-induced cell fusion as well as HIV-1 entry into both CD4 ؉ and CD4 ؊ / GalCer ؉ cells. A structure-activity relationship study showed that: (i) the antiviral activity of soluble analogs of GalCer correlates with V3 loop binding, and (ii) the hydrophobic moiety of the molecule plays an important role in this activity. Taken together, these data show that synthetic analogs of GalCer can inhibit HIV-1 entry into both CD4 ؊ and CD4 ؉ cells through masking of the V3 loop.

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Section: Discussionmentioning

confidence: 99%

Section: Materials-spc3 Ie (Gpgraf)mentioning

confidence: 99%

Section: Anti-hiv-1 Activity Of Ca52(n15)-mentioning

confidence: 99%

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Synthetic Soluble Analogs of Galactosylceramide (GalCer) Bind to the V3 Domain of HIV-1 gp120 and Inhibit HIV-1-induced Fusion and Entry

Fantini¹,

Hammache²,

Delézay³

et al. 1997

Journal of Biological Chemistry

119

107

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“…First, all our TIGMEC lines and all primary cultures of GMEC we tested [24] are easily infected by CAEV, whereas four of eleven human primary epithelial cells and one of three cell lines were found resistant to HIV-1 infection [31]. These results may be explained by an inefficient usage of galactosyl-ceramide rather than the CD4 receptor by HIV-1 to enter these cells [15]. Secondly, the molecular clone and the field isolate of CAEV were found to replicate to high titer in TIG-MEC cells, whereas, HIV-1 replicates only very poorly in human mammary epithelial cells [30,31], as in other epithelial cells from different organs.…”

Section: Discussionmentioning

confidence: 94%

Immortalized goat milk epithelial cell lines replicate CAEV at high level

et al. 2001

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-Primary milk epithelial cells were isolated from CAEV-uninfected goats and three cell lines designated TIGMEC-1, TIGMEC-2 and TIGMEC-3 were established. The three cell lines retained their morphological characteristics of epithelial cells and expressed specific epithelial cytokeratin marker as well as the immortalizing SV40 large T antigen. The kinetics of growth of TIGMEC1, TIG-MEC2 and TIGMEC3 cell lines showed a doubling time of 24-48 hours while the parental cell lines became senescent after the passage 6 in cell culture. Like the parental primary cells, the three cell lines were found to be highly sensitive to CAEV-pBSCA, an infectious molecular clone of CAEV-CO strain, and to a French isolate CAEV-3112. TIGMEC cell lines infected with CAEV-pBSCA became chronically infected producing high virus titers in absence of cytopathic effects. These cell lines may be useful for study of the possible physiological alterations in mammary epithelial cells infected with small ruminant lentiviruses and their consequences on milk quality. On an other hand, these cell lines can be used to study their role in virus transmission and pathogenesis. CAEV / replication / epithelial cell lineRésumé -Des cellules épithéliales du lait immortalisées répliquent le CAEV avec une grande efficacité. Des cellules épithéliales primaires isolées à partir de chèvres non infectées par le CAEV ont été immortalisées pour dériver 3 lignées appelées TIGMEC-1, TIGMEC-2 et TIGMEC-3. Les cellules des 3 lignées ont conservé leurs caractéristiques morphologiques de cellules épithéliales et expriment la cytokératine, un marqueur spécifique des cellules épithéliales et l'antigène immortalisant T du virus SV40. La courbe de croissance des lignées TIGMEC-1, TIGMEC-2 et TIGMEC-3 montre une multiplication des cellules toutes les 24 à 48 heures alors que les cellules parentales ne Vet. Res. 32 (2001) 429-440 429

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“…For example, gp120 have been shown to associate with the dendritic cell-specific ICAM-3-grabbing nonintegrin (also called CD209) (reviewed in Ref. 49), glycolipid galactocerebroside and its sulfated derivative (50,51), glycosaminoglycan heparan sulfate (52,53), placental membrane-binding protein (now called dendritic cell-specific ICAM-3-grabbing nonintegrin) (54), and macrophage mannose receptor (55). Interaction between virus-acquired host cell membrane constituents with their respective cellular counterparts may also generate signaling that might result in a change in the activation status of the cell.…”

Section: Discussionmentioning

confidence: 99%

HIV Type 1 Can Act as an APC upon Acquisition from the Host Cell of Peptide-Loaded HLA-DR and CD86 Molecules

Roy

Martin

Giguère

et al. 2005

The Journal of Immunology

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It is well documented that a wide range of host-derived cell surface constituents is inserted within HIV type 1 (HIV-1) and located on the exterior of the virion. Although no virus-associated protein of host origin has been shown to be absolutely required for virus replication, studies have revealed that many of these proteins are functional and can affect several steps of the virus life cycle. In this study, we found that HIV-1 acquires peptide-loaded class II MHC (MHC-II) and the costimulatory CD86 molecules from the host cell. Moreover, we present evidence that virions bearing such peptide-loaded MHC-II and CD86 proteins can lead to activation of the transcription factors NF-κB and NF-AT in an Ag-specific human T cell line. A linear correlation was found between activation of NF-κB and the amount of peptide-loaded MHC-II molecules inserted within HIV-1. Finally, transcription of unintegrated and integrated HIV-1 DNA was promoted upon exposure of peptide-specific human T cells to viruses bearing both peptide-loaded MHC-II and CD86 proteins. These data suggest that HIV-1 can operate as an APC depending on the nature of virus-anchored host cell membrane components. It can be proposed that HIV-1 can manipulate one of its primary targets through the process of incorporation of host-derived proteins.

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Infection of colonic epithelial cell lines by type 1 human immunodeficiency virus is associated with cell surface expression of galactosylceramide, a potential alternative gp120 receptor.

Abstract: The gastrointestinal tract plays a major role in the pathogenesis and pathophysiology ofinfection by the type

Cited by 235 publications

References 33 publications

Synthetic Soluble Analogs of Galactosylceramide (GalCer) Bind to the V3 Domain of HIV-1 gp120 and Inhibit HIV-1-induced Fusion and Entry

Synthetic Soluble Analogs of Galactosylceramide (GalCer) Bind to the V3 Domain of HIV-1 gp120 and Inhibit HIV-1-induced Fusion and Entry

Immortalized goat milk epithelial cell lines replicate CAEV at high level

HIV Type 1 Can Act as an APC upon Acquisition from the Host Cell of Peptide-Loaded HLA-DR and CD86 Molecules

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