Ball Sarah C, Abraha Awet, Collins Kalonji R, Marozsan Andre J, Baird Heather, Quiñones-Mateu Miguel E, Penn-Nicholson Adam, Murray Michael, Richard Nathalie, Lobritz Michael, Zimmerman Peter A, Kawamura Tatsuyoshi, Blauvelt Andrew, Arts Eric J
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
J Virol. 2003 Jan;77(2):1021-38. doi: 10.1128/jvi.77.2.1021-1038.2003.
Continual human immunodeficiency virus type 1 (HIV-1) evolution and expansion within the human population have led to unequal distribution of HIV-1 group M subtypes. In particular, recent outgrowth of subtype C in southern Africa, India, and China has fueled speculation that subtype C isolates may be more fit in vivo. In this study, nine subtype B and six subtype C HIV-1 isolates were added to peripheral blood mononuclear cell cultures for a complete pairwise competition experiment. All subtype C HIV-1 isolates were less fit than subtype B isolates (P < 0.0001), but intrasubtype variations in HIV-1 fitness were not significant. Increased fitness of subtype B over subtype C was also observed in primary CD4(+) T cells and macrophages from different human donors but not in skin-derived human Langerhans cells. Detailed analysis of the retroviral life cycle during several B and C virus competitions indicated that the efficiency of host cell entry may have a significant impact on relative fitness. Furthermore, phyletic analyses of fitness differences suggested that, for a recombined subtype B/C HIV-1 isolate, higher fitness mapped to the subtype B env gene rather than the subtype C gag and pol genes. These results suggest that subtype B and C HIV-1 may be transmitted with equal efficiency (Langerhans cell data) but that subtype C isolates may be less fit following initial infection (T-cell and macrophage data) and may lead to slower disease progression.
人类免疫缺陷病毒1型(HIV-1)在人群中持续进化和传播,导致HIV-1 M组亚型分布不均。特别是,近年来C亚型在南非、印度和中国的迅速增长引发了人们对C亚型毒株在体内可能更具适应性的猜测。在本研究中,将9株B亚型和6株C亚型HIV-1毒株添加到外周血单核细胞培养物中,进行了完整的两两竞争实验。所有C亚型HIV-1毒株的适应性均低于B亚型毒株(P < 0.0001),但HIV-1适应性的亚型内变异并不显著。在来自不同人类供体的原代CD4(+) T细胞和巨噬细胞中也观察到B亚型比C亚型的适应性增强,但在皮肤来源的人类朗格汉斯细胞中未观察到。对几种B和C病毒竞争过程中逆转录病毒生命周期的详细分析表明,宿主细胞进入效率可能对相对适应性有显著影响。此外,对适应性差异的系统发育分析表明,对于一株重组的B/C亚型HIV-1毒株,更高的适应性映射到B亚型env基因而非C亚型gag和pol基因。这些结果表明,B亚型和C亚型HIV-1可能以相同的效率传播(朗格汉斯细胞数据),但C亚型毒株在初次感染后可能适应性较差(T细胞和巨噬细胞数据),并可能导致疾病进展较慢。