Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Antibody reactivity to HIV-1 Vpu in HIV-1/AIDS patients on highly active antiretroviral therapy

  • 15 Accesses

  • 4 Citations


Human immunodeficiency virus type 1 (HIV-1) Vpu protein promotes both extracellular release of viral particles and degradation of CD4 in the endoplasmic reticulum. The correlation of anti-Vpu antibody (Ab) reactivity to Vpu and AIDS disease progression was studied in 162 HIV-1/AIDS patients after they had received highly active antiretroviral therapy (HAART) for 1 year. Anti-Vpu Ab reactivity was analyzed by Western blot using a recombinant Vpu protein. Results showed that at baseline (prior to initiation of HAART), 31.5% of patients (51/162) had anti-Vpu Ab. The proportion of anti-Vpu Ab in patients with CD4 counts ≥500, 200–500 and <200/mm3 were 40.6, 34.7 and 14.3%, respectively (x 2 test, p<0.05). In addition, decreasing levels of anti-Vpu Ab reactivity were significantly correlated with increasing levels of HIV-1 viral load. After receiving HAART for 1 year, 7 of 111 anti-Vpu Ab-negative patients (6.3%) seroconverted (− → + group) and 8 of 51 anti-Vpu Ab-positive (15.7%) patients became negative (+ → − group). Among 104 anti-Vpu Ab-negative patients, 40 were selected for analysis of thevpu gene. All of them had an intactvpu gene. Patients were further divided into four groups according to their anti-Vpu Ab serostatus and anti-HIV-1 Ab was measured. The results showed that only the anti-Vpu Ab seroconverted group (− → +) had increased serum levels of anti-HIV-1 Abs after 1 year of HAART, while the other three groups (+ → +, − → − and + → −) had decreased serum levels of anti-HIV-1 Abs after 1 year of HAART (p<0.05). In conclusion, the presence of anti-Vpu Ab is associated with improved prognosis following HIV-1 infection, and seroconversion of anti-Vpu Ab in patients on HAART indicates significant recovery of immunity.

This is a preview of subscription content, log in to check access.


  1. 1

    Baudner S, Haupt H, Hubner R. Manufacture and characterization of a new reference preparation for 14 plasma proteins/CRM 470 = RPPHS lot 5. J Clin Lab Anal 8:177–190;1994.

  2. 2

    Chen MY, Maldarelli F, Karczewski MK, Willey RL, Strebel K. Human immunodeficiency virus type 1 Vpu protein induces degradation of CD4 in vitro: The cytoplasmic domain of CD4 contributes to Vpu sensitivity. J Virol 67:3877–3884;1993.

  3. 3

    Chen YM, Lin RH, Fu CY, Lin RY, Syu WJ. Decreasing levels of anti-Nef antibody correlate with increasing viral loads in HIV-1 infected people with differing clinical status. In: Proceedings of the 12th World AIDS Conference. Italy, Monduzzi, vol 2, 627–634;1998.

  4. 4

    Chen YM, Lin RH, Lee CM, Fu CY, Chen SC, Syu WJ. Decreasing levels of anti-Nef antibody correlate with increasing HIV type 1 viral load and AIDS disease progression. AIDS Res Hum Retroviruses 15:43–50;1999.

  5. 5

    Chen YM, Shiu JY, Tzeng SJ, Shih LS, Chen YJ, Lui WY, Chen PH. Characterization of the glycine-N-methyltransferase-gene expression in human hepatocellular carcinoma. Int J Cancer 75:787–793;1998.

  6. 6

    Chen YM, Zhang XQ, Dahl C, Samuel KP, Schooley RT, Essex M, Papas TS. Delineation of type-specific regions on human T-cell leukemia virus envelope glycoproteins. J Immunol 147:2368–2376;1991.

  7. 7

    Chou MJ, Lee TH, Hatzakis A, Mandalaki T, McLane MF, Essex M. Antibody responses in early human immunodeficiency virus type 1 infection in hemophiliacs. J Infect Dis 157:805–811;1988.

  8. 8

    Cohen EA, Terwillinger EF, Sordroski JG, Haseltine WA. Identification of a protein encoded by the vpu gene of HIV. Nature 334:532–534;1988.

  9. 9

    Copeland KF, Heeney JL. T helper cell activation and human retroviral pathogenesis. Microbiol Rev 60:722–742;1996.

  10. 10

    Delwart EL, Shpaer EG, Louwagie J, McCutchan FE, Grez M, Rubsamen-Waigmann H, Mullins JI. Genetic relationships determined by a DNA heteroduplex mobility assay: Analysis of HIV-1 env genes. Science 262:1257–1261;1993.

  11. 11

    Dewar RL, Highbarger HC, Sarmiento MD, Todd JA, Vasudevachari MB, Davey Jr RT, Kovacs JA, Salzman NP, Lane HC, Urdea MS. Application of branched DNA signal amplification to monitor human immunodeficiency virus type 1 burden in human plasma. J Infect Dis 170:1172–1179;1994.

  12. 12

    Emerman M, Malim MH. HIV-1 regulatory/accessory genes: Keys to unraveling viral and host cell biology. Science 280:1880–1884;1998.

  13. 13

    Guan KL, Dixon JE. Eukaryotic proteins expressed inEscherichia coli: An improved thrombin cleavage and purification procedure of fusion proteins with glutathione S-transferase. Anal Biochem 192:262–267;1991.

  14. 14

    Hall TA. BioEdit: A user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98;1999.

  15. 15

    Kerkau T, Bacik J, Yewdell J, Bennink JR, Hünig T, Schimpl A, Schubert U. The human immunodeficiency virus type-1 (HIV-1) Vpu protein interferes with an early step in the biosynthesis of major histocompatibility complex (MHC) class I molecules. J Exp Med 185:1295–1305;1997.

  16. 16

    Kumar S, Tamura K, Jakobsen IB, Nei M. MEGA2: Molecular Evolutionary Genetics Analysis Software. Tempe, Arizona State University, 2001.

  17. 17

    Lee CN, Wang WK, Fan WS, Twu SJ, Chen SC, Sheng MC, Chen MY. Determination of human immunodeficiency virus type 1 subtypes in Taiwan by vpu gene analysis. J Clin Microbiol 38:2468–2474;2000.

  18. 18

    Maldarelli F, Chen MY, Willey RL, Strebel K. Human immunodeficiency virus type 1 Vpu protein is an oligomeric type I integral membrane protein. J Virol 67:5056–5061;1993.

  19. 19

    Matsuda Z, Chou MJ, Matsuda M, Huang JH, Chen YM, Redfield R, Mayer K, Essex M, Lee TH. Human immunodeficiency virus type 1 has an additional coding sequence in the central region of the genome. Proc Natl Acad Sci USA 85:6968–6972;1988.

  20. 20

    Mellors JW, Muňoz A, Qiorgi JV, Margolick JB, Tassoni CJ, Gupta P, Kingsley LA, Todd JA, Saah AJ, Detels R, Phair JP, Rinaldo CR. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 126:946–954;1997.

  21. 21

    Paul M, Mazumder S, Raja N, Jabbar MA. Mutational analysis of the human immunodeficiency virus type 1 Vpu transmembrane domain that promotes the enhanced release of virus-like particles from the plasma membrane of mammalian cells. J Virol 72:1270–1279;1998.

  22. 22

    Reiss P, Lange JMA, de Ronde A, de Wolf F, Dekker J, Danner SA, Debouck C, Goudsmit J. Antibody response to viral protein U (vpu) and R (vpr) in HIV-1-infected individuals. J Acquir Immune Defic Syndr 3:115–122;1990.

  23. 23

    Reiss P, Lange JMA, de Ronde A, de Wolf F, Dekker J, Debouck C, Goudsmit J. Speed of progression to AIDS and degree of antibody response to accessory gene products of HIV-1. J Med Virol 30:163–168;1990.

  24. 24

    Schneider T, Hildebrandt P, Rönspeck W, Weigelt W, Pauli G. The antibody response to the HIV-1 specific ‘out’ (vpu) protein: Identification of an immunodominant epitope and correlation of antibody detectability to clinical stages. AIDS Res Hum Retroviruses 6:943–950;1990.

  25. 25

    Shaw GM, Hahn BH, Arya SK, Groopman JE, Gallo RC, Wong-Staal F. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science 226:1165–1171;1984.

  26. 26

    Smith LM, Sanders JZ, Kaiser RJ, Hughes P, Dodd C, Connell CR, Heiner C, Kent SB, Hood LE. Fluorescence detection in automated DNA sequence analysis. Nature 321:674–679;1986.

  27. 27

    Yan BS, Lee KM, Liu SH, Syu WJ. Characterization of monoclonal antibodies to the 26-kDa glutathione S-transferase ofSchistosoma japonicum. Hybridoma 15:429–433;1996.

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chen, Y.A., Rey, W., Lan, Y. et al. Antibody reactivity to HIV-1 Vpu in HIV-1/AIDS patients on highly active antiretroviral therapy. J Biomed Sci 10, 266–275 (2003). https://doi.org/10.1007/BF02256062

Download citation

Key Words

  • Anti-Vpu antibody
  • lgG subclasses
  • vpu gene
  • Viral load
  • Total lgG
  • Disease progression
  • Highly active antiretroviral therapy
  • AIDS