Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection
Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection
复制标题
DOI：
10.1128/jvi.71.10.7518-7525.1997
复制
发表时间：
1997-10-01
影响因子：
5.4
通讯作者：
Lifson, JD
中科院分区：
文献类型：
--
作者：
Nowak, MA;Lloyd, AL;Lifson, JD
基于抗逆转录病毒治疗期间血浆中病毒粒子相关RNA水平的连续测量，对病毒复制动态的数学建模为人类免疫缺陷病毒1型致病机理带来了新的见解。我们利用猴免疫缺陷病毒(SIV)感染猕猴模型，在初次感染期间和抗逆转录病毒药物(R)-9-(2-膦甲氧基丙基)腺嘌呤(PMPA)治疗期间进行了详细的测量和数学建模。在初次感染的病毒血症高峰消退期间，计算的生产性感染细胞的清除半衰期约为1天，在PMPA治疗期间计算的清除毛发寿命略短。在相同的动物中，在PMPA治疗2周后停止治疗的病毒繁殖率大约是开始治疗前的两倍，这可能反映了治疗过程中易感靶细胞的积累。还估计了SIV感染在体内传播的基本繁殖比(R-0)，它代表在感染开始时从每个生产性感染细胞获得的生产性感染细胞的数量，该参数量化了抗病毒治疗或疫苗接种必须限制病毒初始传播以防止建立慢性播散性感染的程度。因此，这些结果为努力开发针对SIV，进而针对人类免疫缺陷病毒的疫苗提供了重要的指导。
Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis, We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance hair-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 H weeks were approximately twofold greater than those obtained just prier to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R-0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated, This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.