Abstract
BackgroundHIV-1 subtype B’ isolates have been predominantly circulating in China. Their intra- and inter-subtype neutralization sensitivity to autologous and heterologous plasmas has not been well studied.ResultsTwelve HIV-1 B’ clinical isolates obtained from patients were tested for their intra- and inter-subtype neutralization sensitivity to the neutralization antibodies in the plasmas from patients infected by HIV-1 B’ and CRF07_BC subtypes, respectively. We found that the plasmas from the HIV-1 B’-infected patients could potently neutralize heterologous viruses of subtype B’ with mean ID50 titer (1/x) of about 67, but they were not effective in neutralizing autologous viruses of subtype B’ with mean ID50 titer (1/x) of about 8. The plasmas from HIV-1 CRF07_BC-infected patients exhibited weak inter-subtype neutralization activity against subtype B’ viruses with ID50 titer (1/x) is about 22. The neutralization sensitivity of HIV-1 B’ isolates was inversely correlated with the neutralizing activity of plasmas from HIV-1 B’-infected patients (Spearman’s r = −0.657, P = 0.020), and with the number of potential N-glycosylation site (PNGS) in V1-V5 region (Spearman’s r = −0.493, P = 0.034), but positively correlated with the viral load (Spearman’s r = 0.629, P = 0.028). It had no correlation with the length of V1-V5 regions or the CD4+ T cell count. Virus AH259V has low intra-subtype neutralization sensitivity, it can be neutralized by 17b (IC50: 10μg/ml) and 447-52D (IC50: 1.6μg/ml), and the neutralizing antibodies (nAbs) in plasma AH259P are effective in neutralizing infection by the primary HIV-1 isolates with different subtypes with ID50 titers (1/x) in the range of 32–396.ConclusionsThese findings suggest that the HIV-1 subtype B’ viruses may mutate under the immune pressure, thus becoming resistant to the autologous nAbs, possibly by changing the number of PNGS in the V1-V5 region of the viral gp120. Some of primary HIV-1 isolates are able to induce both intra- and inter-subtype cross-neutralizing antibody responses.
Highlights
human immunodeficiency virus type 1 (HIV-1) subtype B’ isolates have been predominantly circulating in China
General characteristics of the study subjects and viral subtypes Viruses were isolated from the peripheral blood mononuclear cells (PBMCs) of 12 HIV-1-infected patients, who are former plasma donors (FPDs) from Anhui province of China
The amino acid (AA) lengths and numbers of potential N-glycosylation site (PNGS) in the V1 to V5 (V1-V5) regions were analyzed by comparing their HIV-1 gp120 sequences
Summary
HIV-1 subtype B’ isolates have been predominantly circulating in China. Their intra- and inter-subtype neutralization sensitivity to autologous and heterologous plasmas has not been well studied. Neutralizing antibodies (nAbs) are likely to be a critical component of protective immunity if a human immunodeficiency virus type 1 (HIV-1) vaccine is to be effective [10]. Most individuals developed nAbs to their own virus (autologous neutralization) within a few months of infection [11], whereas plasmas from chronically-infected. The development of crossreactive nAbs during HIV-1 infection correlates with duration of infection, higher plasma viral RNA load and lower CD4+ T cell counts [13,14,15]. Some studies revealed the mechanisms that HIV-1 escaped from nAbs through extensions of the variable loops of Env, protection of conserved regions from antibody recognition, extensive glycosylation patterns of Env, steric occlusion and conformational masking of receptor binding sites [10,16,18,19,20]
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