Viral dynamics in hepatitis B virus infection
Viral dynamics in hepatitis B virus infection
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DOI：
10.1073/pnas.93.9.4398
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发表时间：
1996-04-30
影响因子：
11.1
通讯作者：
McDade, H
中科院分区：
文献类型：
--
作者：
Nowak, MA;Bonhoeffer, S;McDade, H
用逆转录酶抑制剂拉米夫定治疗慢性乙型肝炎病毒（HBV）感染可导致血浆病毒血症迅速下降，并提供HBV复制的关键动力学常数的估计。我们发现，在持续感染的患者中，HBV颗粒从血浆中被清除，半衰期约为1.0天，这意味着每天有50%的游离病毒群周转。病毒向外周的总释放量约为每天10（11）个病毒颗粒。虽然我们没有直接测量受感染的细胞群，但我们可以通过两种方式估计这些细胞的周转率：(i)通过比较治疗前后的病毒产生率或（ii）通过治疗期间乙型肝炎抗原的下降。这两种独立的方法给出了相同的结果：我们发现产生病毒的细胞的半衰期分布广泛，在不同的患者中从10天到100天不等，这可能反映了免疫反应对感染细胞的裂解率的差异。我们的分析提供了体内HBV复制动力学的定量理解，并对慢性HBV感染的药物治疗和免疫治疗的最佳时机具有指导意义。这项研究也代表了对人类免疫缺陷病毒（HIV）感染动力学的最新发现的比较。平均而言，慢性乙型肝炎病毒携带者的血浆病毒日产量高于艾滋病毒感染者，但艾滋病毒感染者的病毒产生细胞的半衰期要短得多。最引人注目的是，在治疗长达24周的hbv感染患者中没有出现耐药性的迹象。
Treatment of chronic hepatitis B virus (HBV) infections with the reverse transcriptase inhibitor lamivudine leads to a rapid decline in plasma viremia and provides estimates for crucial kinetic constants of HBV replication. We find that in persistently infected patients, HBV particles are cleared from the plasma with a half-life of approximate to 1.0 day, which implies a 50% daily turnover of the free virus population. Total viral release into the periphery is approximate to 10(11) virus particles per day. Although we have no direct measurement of the infected cell mass, we can estimate the turnover rate of these cells in two ways: (i) by comparing the rate of viral production before and after therapy or (ii) from the decline of hepatitis B antigen during treatment. These two independent methods give equivalent results: we find a wide distribution of half-lives for virus-producing cells, ranging from 10 to 100 days in different patients, which may reflect differences in rates of lysis of infected cells by immune responses. Our analysis provides a quantitative understanding of HBV replication dynamics in vivo and has implications for the optimal timing of drug treatment and immunotherapy in chronic HBV infection. This study also represents a comparison for recent findings on the dynamics of human immunodeficiency virus (HIV) infection. The total daily production of plasma virus is, on average, higher in chronic HBV carriers than in HIV-infected patients, but the half-life of virus-producing cells is much shorter in HIV. Most strikingly, there is no indication of drug resistance in HBV-infested patients treated for up to 24 weeks.