Peeters M, Vincent R, Perret J L, Lasky M, Patrel D, Liegeois F, Courgnaud V, Seng R, Matton T, Molinier S, Delaporte E
Laboratoire Retrovirus, Institut de Recherche pour le Developpement, IRD (ORSTOM), Montpellier, France.
J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Feb 1;20(2):115-21. doi: 10.1097/00042560-199902010-00002.
Non-syncytium-inducing (NSI) variants seem to be more readily transmitted than syncytium-inducing (SI) variants, and the switch from NSI to SI during HIV-1 infection seems to be a key determinant to the evolution of AIDS. We investigated eventual differences in the SI capacity on MT-2 cells according to genetic subtypes of HIV-1 and correlated this observations with CD4 counts and duration of HIV infection. In total, 86 patients, most with known date of HIV contamination and infected with different genetic subtypes, have been studied: 11 subtype A, 46 subtype B, 22 subtype C, and 7 subtype E. Multivariate analysis used a Cox's proportional hazards regression. The number and percentage of patients infected with an SI strain were as follows: 3 of 11 (27%) for subtype A, 15 of 46 (33%) for subtype B, 0 of 22 (0%) for subtype C, and 5 of 7 (71%) for subtype E. After adjustment for time after seroconversion and CD4 counts, significantly fewer SI variants were observed in patients infected with subtype C (p < .002) and it was found that subjects infected with subtype E had a higher risk of being infected with an SI strain (rate ratio [RR] = 12.39%; 95% confidence interval [CI] 1.55-98.67; p < .001). Most of the subtype E-infected patients from our study switched from an NSI to SI phenotype early after seroconversion (<4 years). To predict the in vitro presence of SI variants, we scanned V3-loop sequences for mutations at positions 11 and/or 25. Overall, 54 of 55 (98.2%) NSI strains in vitro were predicted NSI, and only 4 of 12 (33.3%) of SI viruses were predicted SI. For patients in whom a switch from an NSI to an SI virus was observed, the SI phenotype could be detected earlier in vitro than by the corresponding V3-loop sequence. No SI strains were observed among patients infected with subtype C; however, longer follow-up is needed to see whether the appearance of SI variants in subtype E or the absence of SI variants in subtype C-infected patients is also associated respectively with a faster or slower progression to AIDS as described for subtype B.
非合胞体诱导（NSI）变异株似乎比合胞体诱导（SI）变异株更容易传播，并且在HIV-1感染过程中从NSI向SI的转变似乎是艾滋病发展演变的一个关键决定因素。我们根据HIV-1的基因亚型调查了MT-2细胞上SI能力的最终差异，并将这一观察结果与CD4细胞计数及HIV感染持续时间相关联。总共研究了86例患者，其中大多数患者已知HIV感染日期且感染了不同的基因亚型：11例为A亚型，46例为B亚型，22例为C亚型，7例为E亚型。多变量分析采用Cox比例风险回归。感染SI毒株的患者数量及百分比情况如下：A亚型11例中有3例（27%），B亚型46例中有15例（33%），C亚型22例中无（0%），E亚型7例中有5例（71%）。在对血清转化后时间和CD4细胞计数进行校正后，感染C亚型的患者中观察到的SI变异株明显较少（p < 0.002），并且发现感染E亚型的受试者感染SI毒株的风险更高（率比[RR] = 12.39%；95%置信区间[CI] 1.55 - 98.67；p < 0.001）。我们研究中的大多数感染E亚型的患者在血清转化后早期（<4年）就从NSI表型转变为SI表型。为了预测SI变异株在体外的存在情况，我们扫描了V3环序列中第11位和/或第25位的突变。总体而言，体外55株NSI毒株中有54株（98.2%）被预测为NSI，而12株SI病毒中只有4株（33.3%）被预测为SI。对于观察到从NSI病毒转变为SI病毒的患者，SI表型在体外比通过相应的V3环序列能更早被检测到。在感染C亚型的患者中未观察到SI毒株；然而，需要更长时间的随访来观察E亚型中SI变异株的出现或C亚型感染患者中SI变异株的缺失是否也分别与向艾滋病进展的更快或更慢相关，如同B亚型的情况那样。
