Graziosi C, Pantaleo G, Butini L, Demarest J F, Saag M S, Shaw G M, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6405-9. doi: 10.1073/pnas.90.14.6405.
HIV-1 replication and viral burden in peripheral blood mononuclear cells (PBMC) have been reported to be high in primary infection but generally very low during the prolonged period of clinical latency. It is uncertain precisely when this transition occurs during the HIV-1 infection and what the relationship is between the changes in HIV-1 replication versus the clearance of infected cells in the overall control of viral replication. In the present study, the kinetics of viral burden (i.e., frequency of HIV-1-infected cells) and replication during primary and early-chronic infection were analyzed in PBMC of four acutely infected individuals. High frequencies of HIV-1-infected cells and high levels of virus replication were observed in PBMC after primary HIV-1 infection. Down-regulation of virus replication in PBMC was observed in all four patients coincident with the emergence of HIV-1-specific immune responses. Other parameters of virus replication, such as circulating plasma p24 antigen and plasma viremia showed similar kinetics. In contrast, a significant decline in viral burden in PBMC was observed in only one of four patients. These results indicate that the down-regulation in the levels of virus replication associated with the clinical transition from acute to chronic infection does not necessarily reflect a reduction in viral burden, thus suggesting the involvement of additional factors. Identification of these factors will be important in elucidating the host mechanisms involved in the early control of HIV-1 infection and disease.
据报道,在初次感染时,外周血单个核细胞(PBMC)中的HIV-1复制和病毒载量很高,但在临床潜伏期的延长阶段通常非常低。目前尚不确定这种转变在HIV-1感染过程中具体何时发生,以及在病毒复制的总体控制中,HIV-1复制的变化与被感染细胞清除之间的关系是什么。在本研究中,对四名急性感染个体的PBMC在初次感染和早期慢性感染期间的病毒载量动力学(即HIV-1感染细胞的频率)和复制情况进行了分析。初次HIV-1感染后,在PBMC中观察到高频率的HIV-1感染细胞和高水平的病毒复制。在所有四名患者中,随着HIV-1特异性免疫反应的出现,均观察到PBMC中病毒复制的下调。病毒复制的其他参数,如循环血浆p24抗原和血浆病毒血症,也表现出类似的动力学。相比之下,在四名患者中只有一名患者的PBMC中的病毒载量出现了显著下降。这些结果表明,与从急性感染到慢性感染的临床转变相关的病毒复制水平下调并不一定反映病毒载量的降低,因此提示还有其他因素的参与。确定这些因素对于阐明宿主在HIV-1感染和疾病早期控制中所涉及的机制将具有重要意义。