Antibody reactivity to HIV-1 Vpu in HIV-1/AIDS patients on highly active antiretroviral therapy.
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 > or =500, 200-500 and <200/mm(3) were 40.6, 34.7 and 14.3%, respectively (chi(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 the VPU gene. All of them had an intact VPU 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.
Chen
Yi-Ming A
YM
AIDS Prevention and Research Center, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. arthur@ym.edu.tw
Rey
Wei-Yu
WY
Lan
Yu-Ching
YC
Lai
Shu-Fen
SF
Huang
Yu-Chuan
YC
Wu
Shiow-Ing
SI
Liu
Tze-Tze
TT
Hsiao
Kwang-Jen
KJ
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology*; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D015153:Blotting, Western; D015704:CD4 Antigens / Q000096:biosynthesis; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism; D016336:Gene Products, vpr / Q000276:immunology*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D010802:Phylogeny; D010957:Plasmids / Q000378:metabolism; D011379:Prognosis; D011994:Recombinant Proteins / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D054325:vpr Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D016336:Gene Products, vpr; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; D005982:Glutathione Transferase