New Insights into the Functionality of a Virion-Anchored Host Cell Membrane Protein: CD28 Versus HIV Type 1

Abstract

It is now well established that the HIV type 1 (HIV-1) incorporates a vast array of host-encoded molecules in its envelope during the budding process. Interestingly, it was demonstrated that the attachment process is accentuated by supplementary interactions between virion-anchored host molecules and their cognate ligands. Such an enhancement of the viral attachment process was found to result in an increase of infectivity for both T and macrophage-tropic strains of HIV-1. Given that previous work indicates that HIV-1 is budding at the site of cell-to-cell contact, a location rich in the costimulatory CD28 glycoprotein, we investigated whether CD28 could be efficiently acquired by HIV-1. We have been able to generate progeny viruses bearing or not bearing on their surfaces host-derived CD28 using our previously described transient transfection and expression system. The physical presence of CD28 was found to markedly increase virus infectivity in a CD28/B7-dependent manner following infection of two human lymphoid cell lines expressing high levels of surface B7-1/B7-2, two natural ligands of CD28. The physiological significance of CD28 incorporation was provided by the observation that an anti-CD28 Ab decreased replication in primary human mononuclear cells of clinical isolates of HIV-1 propagated in such cells. A virus precipitation assay revealed that M-, T-, and dual-tropic clinical strains of HIV-1 produced in primary human mononuclear cells do indeed incorporate CD28. These results show for the first time that HIV-1 can incorporate CD28 and the acquisition of this specific host surface glycoprotein modulates the virus life cycle.

Insertion of Host-Derived Costimulatory Molecules CD80 (B7.1) and CD86 (B7.2) into Human Immunodeficiency Virus Type 1 Affects the Virus Life Cycle

“…However, it is becoming clear that the insertion of some defined host cell membrane components into mature virions has various impacts on the HIV-1 life cycle and/or virus susceptibility to immune defense. For example, CD55 and CD59 contribute to complement resistance (47); HLA-DR, CD28, and some adhesion molecules (e.g., ICAM-1, LFA-1, and VLA-4) increase virus infectivity by facilitating the binding and entry process when the target cell expresses the appropriate counterligand (10,18,23,30); ICAM-1 renders HIV-1 virions less susceptible to antibody-mediated neutralization (17, 44); major histocompatibility complex class II (MHC II) molecules present superantigens, leading to a polyclonal activation of T cells (45); and CD86 results in intracellular signal transduction events which, when coupled with the engagement of the TCR/ CD3 complex, culminate in the nuclear translocation of both NF-B and NFAT (7).…”

“…This scenario was investigated by assessing the internalization of isogenic virions either lacking or bearing host CD80 or CD86 by an HIV-1 entry assay (23). The data shown in Table 1 indicate that HIV-1 entry is more efficient for virions bearing CD80 and CD86 than for isogenic progeny viruses lacking these two host cell membrane constituents.…”

“…The binding of HIV-1 to the cell surface was monitored as described previously (23). Briefly, virus stocks (25 ng of p24) were exposed to 2.5 ϫ 10 5 Jurkat cells for 1 h at 37°C in a total volume of 250 l of complete culture medium.…”

“…More recently, the presence of host-encoded CD28 in the HIV-1 envelope resulted in a close to 20-fold augmentation in virus infectivity when target cells that expressed high levels of CD80 (B7.1) and CD86 (B7.2), two natural ligands of CD28, were used (23).…”

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

“…For instance, CD55 and CD59 molecules have been shown to protect HIV-1 against destruction by complement proteins (2). The acquisition of the costimulatory molecule CD28 has been reported to result in an increase of virus infectivity (3), whereas insertion of host-encoded CD86 enables whole HIV-1 virions to mediate signal transduction events leading to activation of HIV-1 long terminal repeat (LTR) 3 driven gene expression in human CD4 ϩ T cells via the mammalian ubiquitous transcriptional factor NF-B (4). Incorporation of CD54 (ICAM-1) has been reported to promote infection of CD4-negative cells, enhance virus infectivity, and diminish sensitivity to Ab-mediated neutralization (5)(6)(7)(8).…”