Comparative studies on neutralisation of primary HIV-1 isolates by human sera and rabbit anti-V3 peptide sera.
IgG binding to V3 peptides and serum neutralising responses were studied in four HIV-1 infected individuals with progressive disease over a period of 31-70 months. The 18-20 mer peptides comprised residues 299-317 (numbering of HIV1 MN) in the N-terminal half of the V3 loop of the envelope glycoprotein gp120 and were derived from the sequences of autologous, as well as heterologous isolates. All four individuals studied lacked anti-V3 IgG binding to at least one autologous V3 sequence. V3 peptides to which autologous sera lacked binding IgG were all immunogenic in rabbits and induced antisera that were broadly cross-reactive by EIA and broadly cross-neutralising to primary HIV-1 isolates. This indicates that the peptides are immunogenic per se and that the respective human hosts have selective defects in recognising the corresponding V3 sequences. Despite the absence of antibody binding to autologous V3 peptides, the human sera had neutralising antibodies to autologous (three out of four cases), as well as heterologous isolates (all cases). Moreover, in vitro exposure of the patients' isolates to autologous neutralising serum or the homologous rabbit antiserum selected for variants with amino acid substitutions close to the crown of the V3 loop or in regions outside the sequence corresponding to peptides used for immunisation. The amino acid exchanges affected V3 positions known to be antigenic and which are also prone to change successively in infected persons. It is likely that neutralising antibodies recognise both linear and conformational epitopes in the V3 loop. Apparently, there are several, but restricted, numbers of ways for this structure to change its conformation and thereby give rise to neutralisation resistant viruses.
Lawoko
A L
AL
Section of Virology, Department of Medical Microbiology, Lund University, Lund, Sweden. alex.lawoko@alinks.se
Johansson
B
B
Hjalmarsson
S
S
Christensson
B
B
Ljungberg
B
B
Al-Khalili
L
L
Sjölund
M
M
Pipkorn
R
R
Fenyö
E M
EM
Blomberg
J
J
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009500:Neutralization Tests / Q000379:methods; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D011817:Rabbits; D017386:Sequence Homology, Amino Acid
D000914:Antibodies, Viral; D000939:Epitopes; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007074:Immunoglobulin G; D010446:Peptide Fragments