Inhibition of HIV‐1 infection in vitro by murine monoclonal anti‐p24 antibodies

Abstract

Murine monoclonal antibodies (Mabs) to the major core protein p24 of the human immunodeficiency virus type 1 (HIV-1) were tested for their ability to inhibit the replication and spread of the virus in permanent cell cultures (Molt4/8, K37, H9) and in the culture of II-2 stimulated T cells of healthy donors. After addition of ascitic fluid containing monoclonal anti-p24 antibodies or purified anti-p24 antibodies or the respective control to co-cultures of infected and non-infected cells, HIV-1 replication was evaluated by determining the percentage of infected cells and the activity of reverse transcriptase (RT) in cell-free supernatant. In addition, the supernatant's infectivity was determined. FACS analysis demonstrated p24 antigen in about 40% of unfixed HIV-1 infected cells at the cell membrane. Monoclonal anti-p24 antibodies of different epitope specificity added to the cells but not to the virus delayed the spread of HIV-1 infection in permanent cell culture. Furthermore, anti-p24 Mabs inhibited the release of RT-active virus particles by HIV-1 infected cell lines or II-2 stimulated T-lymphocytes, respectively, up to 60%. The mode of action of anti-p24 antibodies after HIV-1 infection is discussed on the basis of the data obtained.

Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activity

“…Whether Gag is exposed on the virion surface remains a subject of debate. Although rare studies [52–54] have detected cell surface p24 on infected cells, these studies have only been conducted on cell lines, and surface expression was only observed at high, non-physiological rates of infection. However, it is possible that Gag may be exposed during delivery of HIV-1 Gag to the plasma membrane for virion assembly [55] , particularly in the setting of early apoptosis when the inner-cell lipid layer flips out to expose phosphotidyl-serine, potentially exposing cytosolic anchored membrane proteins as well [56] .…”

Systematic epitope analysis of the p26 EIAV core protein

“…The biological assays of the pentadecapeptide membrane suggest the existence of two sequences containing epitopes close to the N terminus of the protein (regions 10-24 and 22-36) that overlap H1 (region 20-29, YTTWVNTIQT) and include the surface-exposed residues T21, T22, N25, T26, Q28, and T29. The localization of an epitope in HIV-1 p24 (region 11-25) (VHQAISPRTLNAWVK), where residues P17, R18, W23, and V24 are identical in both EIAV and HIV-1 CAs has been reported (Ferns et al, 1987(Ferns et al, , 1989Franke et al, 1992).Another reactive sequence was found near the N-terminus of the protein, centered in spot 16, region 46-60 (VDCTSEEMNAFLDVV) and formed by residues of the b-turn that connects the two adjacent helices (H2 and H3) and covering H3. The localization of an epitope in HIV-1 p24, region 44-60 that overlaps spot 16 of our p26 pentadecapeptide membrane has been reported (Janvier et al, 1990;Truong et al, 1997).…”

Chemical Modification of Recombinant HIV-1 Capsid Protein p24 Leads to the Release of a Hidden Epitope Prior to Changes of the Overall Folding of the Protein

“…The monoclonal antibody CB4-1 used for the antigen binding studies was raised against recombinant p24-βgalactosidase fusion protein (Grunow et al, 1990). CB4-1 is biologically active, since it is able to inhibit virus spread in cell culture (Franke et al, 1992). Peptide scanning revealed that CB4-1 recognizes the linear peptide epitope GATPQDLNTML (Ho ¨hne et al, 1993).…”