Rodriguez Shaun K, Sarr Abdoulaye Dieng, MacNeil Adam, Thakore-Meloni Seema, Gueye-Ndiaye Aissatou, Traoré Ibrahima, Dia Mamadou C, Mboup Souleymane, Kanki Phyllis J
Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, USA.
J Virol. 2007 May;81(10):5331-8. doi: 10.1128/JVI.02789-06. Epub 2007 Feb 14.
Neutralizing antibody responses against heterologous isolates in human immunodeficiency virus type 1 (HIV-1) and HIV-2 infections were compared, and their relationships with established clinical markers of progression were examined. Neutralizing responses against 7 heterologous primary isolates and 1 laboratory strain were compared between 32 untreated HIV-1-infected subjects and 35 untreated HIV-2-infected subjects using a pseudotyped reporter virus assay. The breadth of the neutralizing response, defined as the proportion of panel viruses positively neutralized by patient plasma, was significantly greater among HIV-2-infected subjects than among HIV-1-infected subjects. Notably, for fully one-third of HIV-2 subjects, all viruses were effectively neutralized in our panel. Magnitudes of responses, defined as reciprocal 50% inhibitory concentration (IC(50)) titers for positive reactions, were significantly greater among HIV-1-infected subjects than among HIV-2-infected subjects. When plasma samples from HIV-1 patients were tested for cross-neutralization of HIV-2 and vice versa, we found that these intertype responses are very rare and their prevalences comparable in both HIV-1 and HIV-2 infection. The significantly higher magnitude of heterologous responses for HIV-1 compared to HIV-2 prompted us to examine associations with viremia, which is known to be significantly higher in HIV-1 infection. Importantly, there was a significant positive correlation between the IC(50) titer and viral load within both the HIV-1 and HIV-2 groups, suggesting heterologous antibodies may be driven by viral replication. We conclude that HIV-2 infection is characterized by a broad, low-magnitude intratype neutralization response, while HIV-1 is characterized by a narrower but higher-magnitude intratype response and that a significant positive association between the IC(50) titer and viremia is common to both HIV-1 and HIV-2 infections.
比较了人类免疫缺陷病毒1型（HIV-1）和HIV-2感染中针对异源分离株的中和抗体反应，并研究了它们与既定疾病进展临床标志物之间的关系。使用假型报告病毒检测法，比较了32名未经治疗的HIV-1感染受试者和35名未经治疗的HIV-2感染受试者针对7种异源原代分离株和1种实验室毒株的中和反应。中和反应的广度定义为患者血浆阳性中和的一组病毒的比例，HIV-2感染受试者中的中和反应广度显著大于HIV-1感染受试者。值得注意的是，在我们的一组病毒中，整整三分之一的HIV-2受试者的所有病毒都被有效中和。反应强度定义为阳性反应的倒数50%抑制浓度（IC(50)）滴度，HIV-1感染受试者中的反应强度显著大于HIV-2感染受试者。当检测HIV-1患者血浆样本对HIV-2的交叉中和作用以及反之亦然时，我们发现这些不同类型间的反应非常罕见，并且在HIV-1和HIV-2感染中的发生率相当。与HIV-2相比，HIV-1的异源反应强度显著更高，这促使我们研究其与病毒血症的关联，已知HIV-1感染中的病毒血症显著更高。重要的是，HIV-1组和HIV-2组中IC(50)滴度与病毒载量之间均存在显著正相关，表明异源抗体可能由病毒复制驱动。我们得出结论，HIV-2感染的特征是广泛、低强度的同型中和反应，而HIV-1的特征是较窄但高强度的同型反应，并且IC(50)滴度与病毒血症之间的显著正相关在HIV-1和HIV-2感染中均常见。
