Serum immunoglobulin A (IgA)-mediated immunity in human immunodeficiency virus type 2 (HIV-2) infection

Abstract

In the present study, we sought to define the importance of serum IgA (sIgA)-mediated immunity in HIV-2 infection. Serum samples from a total of 29 HIV-2-infected patients from Guinea-Bissau (n = 20) and Portugal (n = 9) were studied. Samples from seronegative individuals were used as controls. Antibody reactivity to native and recombinant envelope glycoproteins as well as peptides representing various regions of the envelope glycoproteins was investigated. Furthermore, the capacity of purified IgA to neutralize the HIV-2(SBL6669) strain was tested. All serum samples showed IgA reactivity against whole HIV-2 antigen. Twenty-eight out of 29 IgA samples (96%) reacted with native HIV-2 gp125, 26/29 (90%) with recombinant gp105, and 29/29 (100%) with recombinant gp36. When using peptides, the most prominent IgA reactivity was seen against the peptide representing aa 644-658 of the transmembranous protein gp36, to which 72% of the sera reacted. Purified sIgA antibodies showed neutralizing effects against HIV-2(SBL6669) in 17/29 cases (59%). This work describes the HIV-2-specific sIgA antigenic response. Moreover, our findings show, for the first time, that sIgA may play a role in the in vitro neutralization of HIV-2.

Potent Neutralizing Serum Immunoglobulin A (IgA) in Human Immunodeficiency Virus Type 2-Exposed IgG-Seronegative Individuals

“…We have recently shown that HIV-2-specific serum IgA has the capacity to neutralize a well-documented HIV-2 strain, SBL6669. The serum IgA primarily bound a region within the HIV-2 transmembrane gp36 (amino acids 644 to 658) (35). Taken together, the results of HIV-1 and HIV-2 studies indicate that HIV-specific IgA immune responses directed against envelope proteins with neutralizing capability may be important in host-pathogen interactions.…”

“…IgA was purified from serum on Artocarpus integrifolia agglutinin (Jacalin; Vector, Burlingame, Calif.), and IgG was purified on protein G-Sepharose (Pharmacia, Uppsala, Sweden) as previously described in detail (35). Briefly, a 200-l volume of Jacalin-agarose beads was added to 20 l of serum diluted 1:10 in dilution buffer (2% [vol/vol] Triton X-100, 150 mM NaCl, 600 mM KCl, 5 mM disodium EDTA, pH 7.8).…”

“…A 5-l volume of molecular weight markers was included in each run as a reference (Amersham Laboratories, Amersham, Buckinghamshire, Great Britain). The electrophoresis procedure was performed as detailed before (35).…”

“…Whole HIV-2 antigen, rgp36, rgp105, and native gp125 ELISAs were performed on purified immunoglobulin fractions and whole serum samples as described elsewhere (35). Briefly, microtiter plates (Nunc, Roskilde, Denmark) were coated overnight with whole HIV-2 antigen (0.1 g/well), rgp36 (0.1 g/ well), gp105 (0.1 g/well), or gp125 (0.1 g/well).…”

HIV-2 A-subtype gp125C2-V3-C3 mutations and their association with CCR5 and CXCR4 tropism

“…Furthermore, six immunogenic regions have been identified in the HIV-2 envelope glycoproteins. Three of them are in gp125 (amino acids 234 to 248 in C2, 296 to 337 in V3, and 472 to 507 in C5), and the others are in the ectodomain of gp36 (amino acids 573 to 595, 634 to 649, and 644 to 658) [42][43][44][45][46][47][48][49][50]. Recently, Barroso and his co-workers have shown that the HIV-2 C2 and C3 are well exposed in the envelope complex and are under strong diversifying selection [41].…”