Ostrowski M A, Krakauer D C, Li Y, Justement S J, Learn G, Ehler L A, Stanley S K, Nowak M, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
J Virol. 1998 Oct;72(10):7772-84. doi: 10.1128/JVI.72.10.7772-7784.1998.
Virus replication in a human immunodeficiency virus (HIV)-infected individual, as determined by the steady-state level of plasma viremia, reflects a complex balance of viral and host factors. We have previously demonstrated that immunization of HIV-infected individuals with the common recall antigen, tetanus toxoid, disrupts this steady state, resulting in transient bursts of plasma viremia after immunization. The present study defines the viral genetic basis for the transient bursts in viremia after immune activation. Tetanus immunization was associated with dramatic and generally reversible shifts in the composition of plasma viral quasispecies. The viral bursts in most cases reflected a nonspecific increase in viral replication secondary to an expanded pool of susceptible CD4(+) T cells. An exception to this was in a patient who harbored viruses of differing tropisms (syncytium inducing and non-syncytium inducing [NSI]). In this situation, immunization appeared to select for the replication of NSI viruses. In one of three patients, the data suggested that immune activation resulted in the appearance in plasma of virus induced from latently infected cells. These findings illustrate certain mechanisms whereby antigenic stimulation may influence the dynamics of HIV replication, including the relative expression of different viral variants.
通过血浆病毒血症的稳态水平测定，人类免疫缺陷病毒（HIV）感染者体内的病毒复制反映了病毒和宿主因素的复杂平衡。我们之前已经证明，用常见的回忆抗原破伤风类毒素对HIV感染者进行免疫会破坏这种稳态，导致免疫后血浆病毒血症短暂爆发。本研究确定了免疫激活后病毒血症短暂爆发的病毒遗传基础。破伤风免疫与血浆病毒准种组成的显著且通常可逆的变化有关。在大多数情况下，病毒爆发反映了继发于易感CD4(+) T细胞池扩大的病毒复制非特异性增加。有一名携带不同嗜性病毒（合胞体诱导型和非合胞体诱导型[NSI]）的患者是个例外。在这种情况下，免疫似乎选择了NSI病毒进行复制。在三名患者中的一名患者中，数据表明免疫激活导致潜伏感染细胞诱导产生的病毒出现在血浆中。这些发现阐明了抗原刺激可能影响HIV复制动态的某些机制，包括不同病毒变体的相对表达。
