Summary
The V3 domain is highly variable and induces HIV neutralizing antibodies (NA). Here we addressed the issues of 1) the participation of mutations in V3 in generation of neutralization resistant escape virus in vivo and 2) the applicability of synthetic V3 peptides corresponding to field isolates to induce neutralizing immune sera. Seven peptides corresponding to the V3 region of primary and escape virus from 3 HIV-1 infected patients were synthesized and used for antibody (Abs) studies and immunizations. The anti-V3 Abs titre in patient serum was generally low against peptides corresponding to autologous virus isolated later than the serum sample in contrast to the titre against peptides corresponding to virus isolated earlier than the serum sample. Furthermore, neutralizing anti-V3 monoclonal antibodies (MAbs) raised against V3 peptides from laboratory strains of HIV-1 showed distinct binding patterns against V3 peptides corresponding to sequential primary and escape field isolates, with the strongest reactivity against late isolated escape virus. These observations suggest that the neutralization epitope was influenced by the appearance of mutations. When used as immunogen in rabbits, V3 peptides corresponding to field isolates were highly immunogenic but failed to induce neutralizing or gp120-precipitating Abs. On the contrary, V3 peptide corresponding to the laboratory strain HXB2 induced HIV neutralizing, gp120-precipitating immune serum. In conclusion, these data suggest a participation of the V3 domain in the immunoselection of escape virus, and that V3 on early field virus is less accessible to NA than that on laboratory strains.
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References
Ait-Khaled M, Emery VC (1993) Comparative sequence analysis of HIV-1 LTR and V3 quasispecies present in lymph node (LN) and peripheral blood mononuclear cells (PBMC) of HIV-1 infected individuals. IXth International Congress of Virology, P48–1
Arendrup M, Nielsen C, Hansen J-ES, Pedersen C, Mathiesen L, Nielsen JO (1992) Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies. J Acquir Immune Defic Syndr 5: 303–307
Arendrup M, Sönnerborg A, Svennerholm B, Åkerblom L, Nielsen C, Clausen H, Olofsson S, Nielsen JO, Hansen J-ES (1993) Neutralizing antibody response during human immunodeficiency virus type 1 infection: type and group specificity and viral escape. J Gen Virol 74: 855–863
Ashelford S, Walker R, Harvey E, et al. (1993) Neutralization of patient derived HIV-1 gp120 variants by autologous sera following substitution into an infectious clone. IXth International Congress of Virology, P48–16
Atherton E, Sheppard RC (1989) Solid phase peptide synthesis, a practical approach. IRL Press, Oxford
Cann AJ, Churcher MJ, Boyd M, O'Brian W, Zhao J-Q, Zack J, Chen ISY (1992) The region of the envelope gene of human immunodeficiency virus type 1 responsible for determination of cell tropism. J Virol 66: 305–309
Cloyd MW, Moore BE (1990) Spectrum of biological properties of human immunodeficiency virus (HIV-1) isolates. Virology 174: 103–116
de Jong J-J, Goudsmit J, Keulen W, Klaver B, Krone W, Tersmette M, de Ronde A (1992) Human immunodeficiency virus type 1 clones chimeric for the envelope V3 domain differ in syncytium formation and replication capacity. J Virol 66: 757–765
Donaldson Y, Rebus S, Bell J, Leigh Brown AJ, Simmonds P (1993) Organ-specific differences in populations of HIV-1 env sequence variants in vivo. IXth International Congress of Virology, P48–10
Fouchier RAM, Groenink M, Kootstra NA, Tersmette M, Huisman HG, Miedema F, Schuitemaker H (1992) Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule. J Virol 66: 3183–3187
Gorny MK, Xu J-Y, Gianakakos V, Karwowska S, Williams C, Sheppard HW, Hanson CV, Zolla-Pazner S (1991) Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein. Proc Natl Acad Sci USA 88: 3238–3242
Hansen J-ES, Nielsen C, Arendrup M, Olofsson S, Mathiesen L, Nielsen JO, Clausen H (1991) Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus. J Virol 65: 6461–6467
Laman JD, Schellekens MM, Abacioglu YH, Lewis GK, Tersmette M, Fouchier RAM, Langedijk JPM, Claassen E, Boersma WJA (1992) Variant-specific monoclonal antibodies and group-specific polyclonal human immunodeficiency virus type 1 neutralizing antibodies raised with synthetic peptides from the gp120 third variable domain. J Virol 66: 1823–1831
Langedijk JP, Back NK, Durda PJ, Goudsmit J, Meloen RH (1991) Neutralizing activity of anti-peptide antibodies against the principal neutralization domain of human immunodeficiency virus type 1. J Gen Virol 72: 2519–2526
Langedijk JP, Back NK, Kiney-Thomas E, Bruck C, Francotte M, Goudsmit J, Meloen RH (1992) Comparison and fine mapping of both high and low neutralizing monoclonal antibodies against the principal neutralization domain of HIV-1. Arch Virol 126: 129–146
Leigh Brown AJ, Zhang LQ, Robertson P, Cleland A, Holmes EC, Simmonds P (1993) Effect of virus load and sequence on HIV transmission. IXth International Congress of Virology, W48–1
Moore JP, McKeating JA, Huang Y, Ashkenazi A, Ho DD (1992) Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates. J Virol 66: 235–243
Neurath AR, Strick N (1990) Confronting the hypervariability of an immunodominant epitope eliciting virus neutralizing antibodies from the envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1). Mol Immunol 27: 539–549
Neurath AR, Jiang S, Strick N, Kolbe H, Kieny M-P, Muchmore E, Girard M (1991) Antibody response of chimpanzees immunized with synthetic peptides corresponding to full-length V3 hypervariable loops of HIV-1 envelope glycopoteins. AIDS Res Hum Retroviruses 7: 813–823
Nielsen CM, Bygbjerg IC, Vestergaard BF (1987) Detection of HIV antigens in eluates from whole blood collected on filterpaper. Lancet i: 566–567
Nielsen C, Nielsen CM, Petersen JL, Gøtzsch PC, Pedersen C, Arendrup M, Vestergaard BF (1991) Isolation of HIV from cultures of purified CD4+ lymphocytes. J Virol Methods 35: 15–25
Nielsen C, Pedersen C, Lundgren JD, Gerstoft J (1993) Biological properties of HIV-isolates in primary HIV-infection: consequences for subsequent course of infection. AIDS 7: 1035–1040
Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoint. Am J Hyg 27: 493–497
Sanchez-Palomino S, Rojas JM, Martinez MA, Fenyö EM, Najera R, Domingo E, Lopez-Galindez C (1993) Dilute passage promotes expression of genetic and phenotypic variants of human immunodeficiency virus type 1 in cell culture. J Virol 67: 2938–2943
Schreiber M, Petersen H, Wachsmuth C, Müller H, Hufert F, Schmitz (1993) Infectivity of HIV-1 quasispecies correlates with absence of anti V3 loop antibodies. IXth International Conference of Virology, P14–13
Skinner MA, Ting R, Langlois AJ, Weinhold KJ, Lyerly HK, Javaherian K, Matthews TJ (1988) Characteristics of a neutralizing monoclonal antibody to the HIV envelope glycoprotein. AIDS Res Hum Retroviruses 4: 187–197
Sönnerborg A, Abens J, Johansson B, Strannegård Ö (1990) Detection of HIV-1 by PCR and virus cultivation. J Med Virol 31: 234–240
Sönnerborg A, Bergström T, Johansson B, Håkansson C, Julander I, Norkrans G, Svennerholm B, Strannegård Ö (1991) Demonstration of HIV-1 DNA in immunocompetent HIV-1 antibody positive, but not in seronegative, homosexual men. Immun Infect Dis 1: 85–89
Sundqvist VA, Albert J, Ohlsson E, Hinkula J, Fenyø EM, Wahren B (1989) Human immunodeficiency virus type 1 p24 production and antigenic variation in tissue culture of isolates with various growth characteristics. J Med Virol 29: 170–175
Zwart G, Langedijk H, Hoek L, Jong JJ, Wolfs TFW, Ramautarsing C, Bakker M, Ronde A, Goudsmit J (1991) Immunodominance and antigenic variation of the principal neutralization domain of HIV-1. Virology 181: 481–489
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Arendrup, M., Åkerblom, L., Heegaard, P.M.H. et al. The HIV-1 V3 domain on field isolates: participation in generation of escape virus in vivo and accessibility to neutralizing antibodies. Archives of Virology 140, 655–670 (1995). https://doi.org/10.1007/BF01309956
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DOI: https://doi.org/10.1007/BF01309956