Chang J, Naif H M, Li S, Sullivan J S, Randle C M, Cunningham A L
Virology Department, ICPMR, Westmead Hospital, University of Sydney, National Centre in HIV Research, New South Wales, Australia.
J Virol. 1996 Nov;70(11):7792-803. doi: 10.1128/JVI.70.11.7792-7803.1996.
Biological and genetic variability is a prominent feature of human immunodeficiency virus (HIV) strains, especially in tropism, syncytium formation, and replicative capacity. To determine whether there were variable host cell effects on HIV replication in monocytes, three different strains of low-passage-number monocytotropic blood isolates of HIV and the laboratory-adapted strain Ba-L were inoculated into panels of adherent monocytes drawn from 44 different donors, and peak extracellular HIV p24 antigen titers were compared. The clinical HIV strains showed patterns of either moderate or low-level replication in most donor monocytes (20 to 4,000 pg/ml). However, within this range there was marked variation in peak titers in most donors. HIV type 1 Ba-L replicated in all donor monocytes to much higher levels with less variability (30 to 40 ng/ml). Furthermore, replication of 21 clinical blood-derived strains of HIV in blood monocytes and monocyte-derived macrophages (MDM) from pairs of identical twins and age-matched unrelated donors (URD) of the same sex were compared. In all of the seven pairs of identical twins, the kinetics of replication (measured by extracellular HIV p24 antigen) of panels of four clinical HIV type 1 isolates in monocytes were similar within pairs. However, marked and significant differences in kinetics of HIV production occurred within 10 of the 12 unrelated donor pairs (P = 0.0007). The remaining two URD pairs showed similar kinetic patterns, but only one pair had the same HLA-DR genotype. Similar results were observed with monocytes/MDMs obtained from a second bleed of the same donor. Hence, discordant patterns of HIV replication kinetics between URD monocyte pairs contrasted with concordant patterns in identical twin monocytes. These data strongly suggest a host cell genetic effect on productive viral replication in monocytes and MDMs. So far, no consistent genetic linkage of HIV replication pattern with HLA-DR genotype has been observed.
生物学和基因变异性是人类免疫缺陷病毒（HIV）毒株的一个显著特征，尤其是在嗜性、合胞体形成和复制能力方面。为了确定宿主细胞对HIV在单核细胞中复制是否存在可变效应，将三株不同的低传代单核细胞嗜性血液HIV分离株以及实验室适应株Ba-L接种到来自44个不同供体的贴壁单核细胞中，并比较细胞外HIV p24抗原的峰值滴度。临床HIV毒株在大多数供体单核细胞中表现出中等或低水平复制模式（20至4000 pg/ml）。然而，在此范围内，大多数供体的峰值滴度存在显著差异。1型HIV Ba-L在所有供体单核细胞中复制到更高水平且变异性较小（30至40 ng/ml）。此外，还比较了来自同卵双胞胎和年龄匹配的同性无关供体（URD）的21株临床血液来源的HIV毒株在血液单核细胞和单核细胞衍生巨噬细胞（MDM）中的复制情况。在所有七对同卵双胞胎中，四株临床1型HIV分离株在单核细胞中的复制动力学（通过细胞外HIV p24抗原测量）在双胞胎对之间相似。然而，在12对无关供体中的10对中，HIV产生动力学存在显著差异（P = 0.0007）。其余两对URD表现出相似的动力学模式，但只有一对具有相同的HLA-DR基因型。从同一供体的第二次采血中获得的单核细胞/MDM也观察到了类似结果。因此，URD单核细胞对之间HIV复制动力学的不一致模式与同卵双胞胎单核细胞中的一致模式形成对比。这些数据强烈表明宿主细胞基因对单核细胞和MDM中病毒的有效复制有影响。到目前为止，尚未观察到HIV复制模式与HLA-DR基因型之间一致的基因连锁关系。
