Analysis of the human immunodeficiency virus type 1 envelope protein interaction with the CD4 host cell receptor

Malvoisin, Etienne; Wild, Fabian

doi:10.1099/0022-1317-75-4-839

Cited by 14 publications

(11 citation statements)

References 28 publications

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“…Our observations on the oligomerization of nCD4 support previous predictions from the crystal structure [18,31], observations on sheep CD4 [40,41] and on CD4 transfectants [43]. This also complements the oligomeric structures of other Ig superfamily members (e. g. CD8) [44,45], and of the CD4-associating membrane protein, TCR [46], and of the CD4 ligands, MHC class II [34], IL-16 [5,6] and HIV gp120 [33].…”

Section: Mt-4 and Cem Cells Of Lymphocytoid Lineage And Of Monocytsupporting

confidence: 89%

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Direct evidence for native CD4 oligomers in lymphoid and monocytoid cells

et al. 1999

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CD4 is expressed by T lymphocytes and monocytes and is generally considered a monomer even though its structure was originally modelled on the REI Bence‐Jones homodimer. However, native CD4 was demonstrated as both monomer and dimers of 55 and 110 kDa in lymphoid and monocytoid cells by immunoprecipitation and immunoblotting after solubilization with alkylating (iodoacetamide) or reducing (dithiothreitol, 2‐mercaptoethanol) reagents. Full reduction yielded only the 55‐kDa monomeric form. Purified CD4 oligomers from CEM‐T4 cells were also resolved as homodimers by MALDI‐Tof mass fingerprinting after tryptic digestion. Cell treatment with the membrane impermeable, free‐thiol reactive, 5,5′‐dithiobis‐2‐nitrobenzoic acid enhanced cell surface CD4 dimers and tetramers. The interaction sites producing dimerization were probably in the D4 domain as OKT4 inhibited self association of recombinant CD4 (rCD4). Oligomerization of rCD4 by glutathione and thioredoxin indicates that thiol exchange interactions were responsible. Enhanced CD4 dimer expression was also observed after PMA (20 ng/ml) activation of THP‐1 cells. These findings demonstrate that different quaternary forms of CD4 such as monomers, homodimers and tetramers are expressed by T lymphocytes and monocytes/macrophages.

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Section: Mt-4 and Cem Cells Of Lymphocytoid Lineage And Of Monocytsupporting

confidence: 89%

“…The primary HIV gp120 binding site on CD4 resides on the CDR2-like region of the N-terminal (D1) domain (aa [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] [23][24][25][26][27][28]. Mutational analysis has shown the most important contact residues to be Phe 43, Lys 46 and Arg 59.…”

Section: Introductionmentioning

confidence: 99%

Direct evidence for native CD4 oligomers in lymphoid and monocytoid cells

et al. 1999

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“…Furthermore, the concentration dependency of sCD4 was essentially the same as that of antibody induced AME, suggesting that cross-linking is required for sCD4 induced AME (Sullivan et al, 1995). It is not clear, however, how sCD4, which is a monomeric structure (Malvoisin & Wild, 1994), may cause cross-linking. We postulate that either sCD4 dimerizes with membrane associated proteins that also bind to HIV-1 gp120, or that more than one recognition site exists between gp120 and sCD4.…”

Section: Discussionmentioning

confidence: 99%

Modulation of primary human immunodeficiency virus type 1 envelope glycoprotein-mediated entry by human antibodies.

Schutten¹,

Andeweg²,

Rimmelzwaan³

et al. 1997

Journal of General Virology

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Recently, we and others have shown that the interaction between envelope specific antibodies and primary human immunodeficiency virus type 1 (HIV-1) isolates may result in either inhibition or enhancement of virus entry. The outcome proved to be determined by the virus isolate rather than by the specificity of the antiserum used. To study the mechanism underlying this phenomenon, a series of HIV-1 envelope glycoproteins from closely related primary virus isolates of different syncytium inducing phenotypes, together with chimeras of these proteins, were tested in an envelope transcomplementation assay for their sensitivity to either antibody mediated inhibition or enhancement of HIV-1 entry. Based on the observation that, in contrast to the inhibition of HIV-1 entry, antibody mediated enhancement was not temperature de-

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“…These interactions between the BLV envelope molecules appear weak since the TM protein is very easily lost during the purification of gp51 (41). For the same reason, it is not possible to analyze the oligomerization of gp51 and gp30 after centrifugation of the complexes on sucrose gradients as it has been described for other envelope proteins (42)(43)(44)(45). However, oligomerization of BLV envelope proteins is not disrupted after centrifugation on metrizamide gradients (41).…”

Section: Mutations Within the Immunosuppressive Region Affect Cellmentioning

confidence: 99%

Conservative Mutations in the Immunosuppressive Region of the Bovine Leukemia Virus Transmembrane Protein Affect Fusion but Not Infectivity in Vivo

Gatot

Callebaut²,

Mornon³

et al. 1998

Journal of Biological Chemistry

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Many retroviruses, including bovine leukemia virus (BLV), contain a highly conserved region located about 40 amino acids downstream from the fusion peptide within the sequence of the external domain of the transmembrane (TM) protein. This region is notably thought to be involved in the presentation of the NH 2 -terminal peptide to allow cell fusion. By using hydrophobic cluster analysis and by analogy with the influenza A hemagglutinin structures, the core of the TM structure including this particular region was predicted to consist, in the BLV and other retroviral envelope proteins, of an ␣-helix followed by a loop region, both docked against a subsequent ␣-helix that forms a triple-stranded coiled coil. The loop region could undergo, as in hemagglutinin, a major refolding into an ␣-helix integrating the coiled coil structure and putting the fusion peptide to one tip of the molecule. Based on this model, we have identified amino acids that may be essential to the BLV TM structure, and a series of mutations were introduced in the BLV env gene of an infectious molecular clone. A first series of mutations was designed to disturb the coiled coil structure (substitutions with proline residues), whereas others would maintain the general TM structure. When expressed by Semliki Forest virus recombinants, all the mutated envelope proteins were stable and efficiently synthesized in baby hamster kidney cells. Both proline-substituted and conservative mutants were strongly affected in their capacity to fuse to CC81 indicator cells. In addition, it appeared that the integrity of the TM coiled coil structure is essential for envelope protein multimerization, as analyzed by metrizamide gradient centrifugation. Finally, to gain insight into the role of this coiled coil in the infectious potential of BLV in vivo, the mutated TM genes were introduced in an infectious and pathogenic molecular clone and injected into sheep. It appeared that only the conservative mutations (A60V and A64S) allowed maintenance of viral infectivity in vivo. Since these mutations destroyed the ability to induce syncytia, we conclude that efficient fusion capacity of the recombinant envelopes is not a prerequisite for the infectious potential of BLV in vivo. Viral propagation of these mutants was strongly affected in some of the infected sheep. However, the proviral loads within half of the infected animals (2 out of 2 for A60V and 1 out of 4 for A64S) were close to the wild-type levels. In these sheep, it thus appears that the A60V and A64S mutants propagate efficiently despite being unable to induce syncytia in cell culture.The infectivity of enveloped viruses is thought to be mediated by surface glycoproteins that are responsible for the recognition of the target cell and for the fusion of both viral and cellular membranes (1). The envelope proteins of the retroviruses are composed of the following two subunits: the extracellular (SU) 1 protein that binds to the receptor and the transmembrane (TM) glycoprotein that anchors the envelope complex into t...

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Analysis of the human immunodeficiency virus type 1 envelope protein interaction with the CD4 host cell receptor

Cited by 14 publications

References 28 publications

Direct evidence for native CD4 oligomers in lymphoid and monocytoid cells

Direct evidence for native CD4 oligomers in lymphoid and monocytoid cells

Modulation of primary human immunodeficiency virus type 1 envelope glycoprotein-mediated entry by human antibodies.

Conservative Mutations in the Immunosuppressive Region of the Bovine Leukemia Virus Transmembrane Protein Affect Fusion but Not Infectivity in Vivo

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