Characterization of the African HIV-1 isolate CBL-4 (RUT) by partial sequence analysis and virus neutralization with peptide antibody and antisense phosphate-methylated DNA

Goudsmit, Jaap; Geelen, J. L. M. C.; Keulen, Wilco; Notermans, Daan W.; Kuiken, Carla; Ramautarsing, Chitra; Smit, L.; Koole, Leo Lh; M, van Genderen; Buck, HM Henk

doi:10.1097/00002030-199006000-00010

Cited by 16 publications

(7 citation statements)

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“…Early studies of the immunological structures of HIV-1 and SIV envelope proteins suggested differences between the two viruses with respect to the antigenicity and immunogenicity of the V3 loop (18,19,24,39,62). V3 region-directed antibodies from HIV-infected individuals were able to efficiently neutralize laboratory-adapted strains of HIV, leading researchers to call the V3 loop the principal neutralizing determinant (62).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ability of the V3 Loop of Simian Immunodeficiency Virus To Serve as a Target for Antibody-Mediated Neutralization: Correlation of Neutralization Sensitivity, Growth in Macrophages, and Decreased Dependence on CD4

Means

Matthews

Hoxie

et al. 2001

J Virol

106

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To better define the effects of sequence variation and tropism on the ability of the simian immunodeficiency virus SIVmac V3 loop to act as a target of antibody-mediated neutralization, a series of experiments were performed. Three SIV strains, SIVmac239, SIVmac316, and SIVmac155/T3, each with defined differences in env sequence and tropism, were used to construct a panel of viruses chimeric for a portion of envelope that includes the V2 and V3 regions. Peptides with sequences corresponding to the V3 loops of the parental viruses were used to immunize rabbits. The polyclonal rabbit antibodies and plasma from SIVmac239-infected animals were then used to assess the neutralization sensitivity of the parental and chimeric viruses. One of the parental viruses, SIVmac316, which is able to replicate to high titer in alveolar macrophages and can infect cells in a CD4-independent fashion, was highly sensitive to neutralization by plasma from SIVmac-infected rhesus macaques, with average 50% neutralization titers of 1:20,480; this same strain was also sensitive to neutralization by the anti-V3 loop peptide sera. Other parental and chimeric viruses were less sensitive to neutralization with this same panel of antibodies, but as seen with SIVmac316, those viruses that were able to productively replicate in alveolar macrophages were more sensitive to antibody-mediated neutralization. To further define the amino acids involved in increased sensitivity to neutralization, a panel of viruses was constructed by changing envelope residues in SIVmac316 to the corresponding SIVmac239 amino acids. The increased neutralization sensitivity observed for SIVmac316 was mapped principally to three amino acid changes spread throughout gp120. In addition, the increased sensitivity to neutralization by V3-directed antibodies correlated with the ability of the various viruses to replicate to high levels in alveolar macrophage cultures and a CD4-negative cell line, BC7/CCR5. These results demonstrate that the V3 loop of SIVmac Env can act as an efficient target of neutralizing antibodies in a fashion that is highly dependent on sequence context. In addition, these studies suggest a correlation between decreased dependence on CD4 and increased sensitivity to antibody-mediated neutralization.

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Section: Discussionmentioning

confidence: 99%

“…Historically, the V3 loop of HIV type 1 (HIV-1) was initially identified as the principal neutralizing determinant of the virus (18,19,39,62). In analogous studies, the V3 loop of SIV was found not to be a target of neutralizing antibodies (23,24,51).…”

mentioning

confidence: 99%

Ability of the V3 Loop of Simian Immunodeficiency Virus To Serve as a Target for Antibody-Mediated Neutralization: Correlation of Neutralization Sensitivity, Growth in Macrophages, and Decreased Dependence on CD4

Means

Matthews

Hoxie

et al. 2001

J Virol

106

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“…HIV-1 CBL-4 was poorly neutralized (N &! l 100 µg\ml), although its V3 loop tip sequence (GXXGPGRA) differs only by the substitution of G for I (Goudsmit et al, 1990). As free MicroAb or MAb were removed in all these assays after virus or virus-antibody complexes had been incubated with cells, it seems that the neutralization obtained was not against progeny virus, as proposed by Levi et al (1993).…”

Section: Neutralization By Syncytium-inhibition Inhibition Of P24 Prmentioning

confidence: 91%

“…HIV-1 B clade strains IIIB, RF, MN, HXB-2D (a molecular clone of IIIB) and the unclassified CBL-4 (Goudsmit et al, 1990) were obtained from the MRC AIDS Reagent Project. These were propagated by co-cultivating chronically infected H9 cells and uninfected H9 cells.…”

Section: Methodsmentioning

confidence: 99%

Properties and mechanism of action of a 17 amino acid, V3 loop-specific microantibody that binds to and neutralizes human immunodeficiency virus type 1 virions.

Jackson

Levi

Wahrén

et al. 1999

Journal of General Virology

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Only two virus-neutralizing peptide microantibodies (MicroAbs) have been described and little is known about their mode of action. This report concerns a 17 amino acid cyclized MicroAb, derived from the third complementarity-determining region of the heavy chain of MAb F58 (IgG1), that recognizes the same minimum epitope in the V3 loop of the gp120 envelope protein of human immunodeficiency virus type 1 (HIV-1) as the MAb. The MicroAb was able to bind to and neutralize free virus particles. It was up to 5-fold more efficient in mass terms than F58 IgG and its neutralization rate on a molar basis was only 32-fold lower. The mechanism of neutralization of the MicroAb was also investigated. A high level of neutralization (99 %) occurred without any significant decrease in attachment of virus to target C8166 cells. Neutralized virus attached to CD4, the HIV-1 primary receptor. Fusion of virions to cells was partially inhibited by the MicroAb, whereas F58 IgG has been shown to inhibit fusion significantly. Thus, neutralization by the MicroAb appears to be mediated, at least in part, by inhibition of fusion. Control peptides, in which the tyrosine at position 5 or 6 was deleted or changed to phenylalanine, showed no antiviral activity, attesting to the specificity of interaction of the MicroAb with the virion. It therefore appears that the MicroAb acts like an immunoglobulin. The data also show that the MicroAb/MAb F58 epitope on the V3 loop is not involved in attachment of virus to CD4 but is required for subsequent events in early infection.

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“…The first attempts using ASOs for antigen manipulation started in 1990. Goudsmit´s group used a phosphate-methylated ASO complementary to the tat responsive region (TAR) of the HIV-1 isolate CBL-4 (RUT) to reduce the viral infectivity [114,115]. However, some technical errors and interpretation of results that were subsequently corrected by the same authors caused the retraction of the article published in Science [116], as well as the conclusion issued that the observed inhibitory effect of viral infectivity should be ascribed to the phosphate methylation of natural DNA.…”

Section: Antigen Modificationmentioning

confidence: 99%

Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement

et al. 2020

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Antisense oligonucleotides (ASOs) are synthetically prepared short single-stranded deoxynucleotide sequences that have been validated as therapeutic agents and as a valuable tool in molecular driving biology. ASOs can block the expression of specific target genes via complementary hybridization to mRNA. Due to their high specificity and well-known mechanism of action, there has been a growing interest in using them for improving vaccine efficacy. Several studies have shown that ASOs can improve the efficacy of vaccines either by inducing antigen modification such as enhanced expression of immunogenic molecules or by targeting certain components of the host immune system to achieve the desired immune response. However, despite their extended use, some problems such as insufficient stability and low cellular delivery have not been sufficiently resolved to achieve effective and safe ASO-based vaccines. In this review, we analyze the molecular bases and the research that has been conducted to demonstrate the potential use of ASOs in vaccines.

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Characterization of the African HIV-1 isolate CBL-4 (RUT) by partial sequence analysis and virus neutralization with peptide antibody and antisense phosphate-methylated DNA

Cited by 16 publications

References 0 publications

Ability of the V3 Loop of Simian Immunodeficiency Virus To Serve as a Target for Antibody-Mediated Neutralization: Correlation of Neutralization Sensitivity, Growth in Macrophages, and Decreased Dependence on CD4

Ability of the V3 Loop of Simian Immunodeficiency Virus To Serve as a Target for Antibody-Mediated Neutralization: Correlation of Neutralization Sensitivity, Growth in Macrophages, and Decreased Dependence on CD4

Properties and mechanism of action of a 17 amino acid, V3 loop-specific microantibody that binds to and neutralizes human immunodeficiency virus type 1 virions.

Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement

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