Sonza S, Kiernan R E, Maerz A L, Deacon N J, McPhee D A, Crowe S M
AIDS Pathogenesis Research Unit, National Centre for HIV Virology Research, Macfarlane Burnet Centre for Medical Research Melbourne, Australia.
J Leukoc Biol. 1994 Sep;56(3):289-93. doi: 10.1002/jlb.56.3.289.
Cytocidal retrovirus infection is characterized by rapid accumulation of unintegrated viral DNA forms. These are thought to be generated by multiple rounds of reinfection and have been suggested to play a central role in cytopathogenesis. Here we have reviewed the work done in this area with HIV-1, mostly using acutely and chronically infected T cell and monocytic cell lines and in some cases T cells blocked at S phase of the cell cycle by aphidicolin treatment. To these studies, we have compared our findings with HIV-1 infected primary peripheral blood monocyte-derived macrophages and untreated and growth-arrested MT-2 cells, two biologically disparate cell populations. Using 1- and 2-long terminal repeat (LTR) circular forms as indicators of unintegrated viral DNA, we found similar rapid accumulation in both untreated and growth-arrested MT-2 cells. In contrast, we found much lower levels in monocyte/macrophages. Our findings suggest that accumulation of unintegrated viral DNA does not require virus production and reinfection in growth-arrested T cells. The significantly lower levels found in monocyte/macrophages may reflect superinfection resistance, allowing the maintenance of a persistent infection.
细胞病变性逆转录病毒感染的特征是未整合的病毒DNA形式迅速积累。这些被认为是由多轮再感染产生的，并被认为在细胞病变发生过程中起核心作用。在此，我们回顾了在该领域针对HIV-1所开展的工作，主要使用急性和慢性感染的T细胞及单核细胞系，在某些情况下还使用了通过阿非迪霉素处理而阻滞在细胞周期S期的T细胞。对于这些研究，我们将我们的发现与HIV-1感染的原代外周血单核细胞衍生的巨噬细胞以及未处理和生长停滞的MT-2细胞（两种生物学上不同的细胞群体）进行了比较。使用1-和2-长末端重复序列（LTR）环状形式作为未整合病毒DNA的指标，我们发现在未处理和生长停滞的MT-2细胞中都有类似的快速积累。相比之下，我们在单核细胞/巨噬细胞中发现的水平要低得多。我们的发现表明，在生长停滞的T细胞中，未整合病毒DNA的积累不需要病毒产生和再感染。在单核细胞/巨噬细胞中发现的显著较低水平可能反映了超级感染抗性，从而允许维持持续性感染。
