Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees

Nara, Peter L.; Smit, L.; Dunlop, Nancy M.; Hatch, W.; Merges, Michael; Waters, David J.; Kelliher, JC; Gallo, Robert C.; Fischinger, Peter J.; Goudsmit, Jaap

doi:10.1128/jvi.64.8.3779-3791.1990

Cited by 219 publications

(66 citation statements)

References 56 publications

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“…Although the extent of antibody crossreactivity decreased with increasing number of substitutions in the V3 tip sequence IGPGR, the hierarchy of reactivity among the various peptides was not always related to the degree of homology with respect to the entire chimeric sequence. For instance, antibody binding to the SC peptide in BIAcore TM was lower than to the WMJ2, SF2 and 4071 peptides ( Table 1), indicating that flanking regions of the sequence GPGR are involved in the antigenicity of the V3 region, a finding in agreement with previous studies [11,16,33].…”

Section: Discussionsupporting

confidence: 91%

Cross-reactive potential of rabbit antibodies raised against a cyclic peptide representing a chimeric V3 loop of HIV-1 gp120 studied by biosensor technique and ELISA

Richalet-Sécordel

Deslandres

Plaué³

et al. 1994

FEMS Immunol Med Microbiol

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Rabbit antibodies were induced against a free cyclic peptide representing the chimeric sequence of a consensus V3 loop of HIV-1 gp120. The reactivity of these antibodies was tested in a biosensor system (BIAcore, Pharmacia AB, Uppsala, Sweden) and in ELISA with the peptide immunogen in its cyclic and linear forms, as well as with peptides corresponding to the V3 region of different HIV-1 variants. The antibodies reacted with all the peptides tested both in ELISA and in biosensor assays and recognized the cyclic form of the chimeric peptide better than the linear form. Although antibodies raised against the V3 region of particular HIV-1 variants cross-react with other HIV-1 strains, it seems that the use of a chimeric peptide as immunogen improved the cross-reactivity spectrum of recognition of the antibodies. The anti-V3 antibodies were also tested for their ability to neutralize in vitro four HIV-1 laboratory strains. Only the HIVMN variant was found to be neutralized. Compared to conventional solid phase immunoassays, the BIAcore presents several advantages for measuring the differential reactivity of peptide analogues. In view of their broadly cross-reactive potential, antibodies raised against a consensus sequence should be useful in immunodiagnosis of viral antigenic variants.

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Section: Discussionsupporting

confidence: 91%

Cross-reactive potential of rabbit antibodies raised against a cyclic peptide representing a chimeric V3 loop of HIV-1 gp120 studied by biosensor technique and ELISA

Richalet-Sécordel

Deslandres

Plaué³

et al. 1994

FEMS Immunol Med Microbiol

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show abstract

“…However, this hypothesis is far too simplistic. Several longitudinal studies [32,33] have shown the occurrence of viral neutralization escape in the presence of conserved V3 linear sequence. In addition, it has recently been shown that neutralization of divergent HIV isolates might be due to antibodies recognizing other regions than V3, which may be linear or conformational [34,35].…”

Section: Discussionmentioning

confidence: 99%

Antibody-dependent cellular cytotoxicity and neutralizing activity in sera of HIV-1-infected mothers and their children

Broliden

Sievers

Tovo

et al. 1993

Clinical and Experimental Immunology

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SUMMARYThe prognostic and protective role of antibodies mediating cellular cytotoxicity (ADCC) and neutralization was evaluated in sera of HIV-1-infected mothers and their consecutively followed children. The presence and titres of ADCC mediating and/or neutralizing antibodies in maternal sera did not predict HIV-1 infection in their respective children. No significant diflFerence in the sera from the children was seen when comparing the presence of neutralizing antibodies between the uninfected and infected children. Stratification of the infected group according to clinical status revealed differences. Only one of 24 AIDS patients had a high neutralizing titre against IIIB. Four patients had a very low titre and the remaining had no detectable neutralizing antibodies at all. In contrast, 10/17 infected non-AIDS children had neutralizing antibodies. Similarly, no significant difference was seen when comparing the presence of ADCC-mediating antibodies between the uninfected and the infected group of children. However, a significantly higher frequency of ADCC was seen in the seropositive non-AIDS children compared with the AIDS children. This study clearly shows that the presence of antibodies mediating ADCC and neutralization in infected children, 0-2 years old, is associated with a better clinical status and delayed disease progression.

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“…Escape of HIV-1 from humoral immune response is well docu-mented. It was assumed that escape might be due to extensive viral replication, leading to mutants no longer recognized by the immune system [18,25,26]. In keeping this theory is the close relationship between the outgrowth of certain virus variants and the lack of the corresponding V3-specific antibody.…”

Section: Discussionmentioning

confidence: 99%

Escape of HIV-1 is associated with lack of V3 domain-specific antibodies in vivo

Schreiber

Müller

Wachsmuth

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThis study was performed to analyse correlates of viral escape in AIDS patients. Peripheral blood mononuclear cells (PBMC) from HIV ¹ donors were inoculated with AIDS patients' serum to detect neutralization-resistant cell-free virus. Infectious virus was detected by polymerase chain reaction (PCR) and analysed by sequencing the V3 region. The escaped virus species was compared with all V3 virus variants found in the patients' PBMC and plasma. In one patient escaped virus was also compared with variants found in CD4 þ T cells isolated by FACS from blood, spleen and lymph node. The frequency of the virus variants was determined by cloning and sequence analysis of 20 V3 clones for each PCR amplification. To monitor anti-V3 antibodies by ELISA, each V3 sequence was expressed as fusion with glutathione S-transferase (GST-V3). In our AIDS patients, a V3-directed antibody response against the infectious virus V3 loop was not detectable. In contrast, virus variants unable to infect the donor PBMC in vitro were well recognized by homologous V3-directed antibody. After an interval of 1 year the frequency of these variants clearly decreased, while at the same time the escaped variants grew out and finally represented the predominant viral species both in plasma and PBMC. The infectious variants lacking V3 antibody response were also predominant in CD4 þ T cells in spleen and lymph node. Our data indicate that the escape of virus variants is closely related to the lack of V3-directed antibody.

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Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees

Cited by 219 publications

References 56 publications

Cross-reactive potential of rabbit antibodies raised against a cyclic peptide representing a chimeric V3 loop of HIV-1 gp120 studied by biosensor technique and ELISA

Cross-reactive potential of rabbit antibodies raised against a cyclic peptide representing a chimeric V3 loop of HIV-1 gp120 studied by biosensor technique and ELISA

Antibody-dependent cellular cytotoxicity and neutralizing activity in sera of HIV-1-infected mothers and their children

Escape of HIV-1 is associated with lack of V3 domain-specific antibodies in vivo

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