State Key Laboratory for Infection Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention (China-CDC), Beijing, China.
Virol J. 2013 Jan 5;10:10. doi: 10.1186/1743-422X-10-10.
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.
Twelve 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.
These 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.
在中国，HIV-1 亚型 B' 分离株一直占主导地位。尚未对其自体和异体血浆的种内和种间中和敏感性进行充分研究。
对来自患者的 12 株 HIV-1 B' 临床分离株进行了检测，以评估其对感染 HIV-1 B' 和 CRF07_BC 亚型患者的血浆中中和抗体的种内和种间中和敏感性。我们发现，来自 HIV-1 B' 感染患者的血浆可以有效地中和异源 B' 亚型病毒，其平均 ID50 滴度（1/x）约为 67，但对自体 B' 亚型病毒的中和作用不强，平均 ID50 滴度（1/x）约为 8。来自 HIV-1 CRF07_BC 感染患者的血浆对 B' 亚型病毒具有较弱的种间中和活性，其 ID50 滴度（1/x）约为 22。HIV-1 B' 分离株的中和敏感性与感染 HIV-1 B' 患者的血浆中和活性呈负相关（Spearman's r = -0.657，P = 0.020），与 V1-V5 区潜在 N-糖基化位点（PNGS）的数量呈负相关（Spearman's r = -0.493，P = 0.034），但与病毒载量呈正相关（Spearman's r = 0.629，P = 0.028）。它与 V1-V5 区的长度或 CD4+T 细胞计数无关。病毒 AH259V 具有较低的种内中和敏感性，可被 17b（IC50：10μg/ml）和 447-52D（IC50：1.6μg/ml）中和，AH259P 血浆中的中和抗体（nAbs）可有效中和不同亚型的原发性 HIV-1 分离株的感染，ID50 滴度（1/x）范围为 32-396。
这些发现表明，HIV-1 亚型 B' 病毒可能在免疫压力下发生突变，从而对自体 nAbs 产生耐药性，可能是通过改变病毒 gp120 的 V1-V5 区的 PNGS 数量。一些原发性 HIV-1 分离株能够诱导种内和种间交叉中和抗体反应。
