Quantitating the Multiplicity of Infection with Human Immunodeficiency Virus Type 1 Subtype C Reveals a Non-Poisson Distribution of Transmitted Variants
Quantitating the Multiplicity of Infection with Human Immunodeficiency Virus Type 1 Subtype C Reveals a Non-Poisson Distribution of Transmitted Variants
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DOI：
10.1128/jvi.02132-08
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发表时间：
2009-04-15
影响因子：
5.4
通讯作者：
Williamson, C.
中科院分区：
文献类型：
--
作者：
Abrahams, M. -R.;Anderson, J. A.;Williamson, C.
确定成功传播的变异体的特定遗传特征可能对开发有效的疫苗和杀微生物剂干预措施至关重要。虽然人类免疫缺陷病毒的传播与人口瓶颈有关，但不同因素对传播病毒多样性的影响程度尚不清楚。我们在这里估计69名异性恋男性和女性原发性C亚型感染的传播变异的数量。从使用单基因组扩增方法获得的1，505个env序列中，我们发现78%的感染涉及单变异传播，22%涉及多变异传播（中位数为3）。我们发现的突变选择细胞毒性T淋巴细胞或抗体逃逸的证据和高患病率的重组感染的多个变种，代表另一个潜在的逃逸途径，在这些个人。在对171起B和C亚型传播事件的联合分析中，我们发现，感染一种以上变异体并不遵循泊松分布，这表明单个病毒体的传播不能被视为独立事件，每个事件发生的概率都很低。虽然大多数传播是由单一感染单位引起的，但多种变异传播占传播事件的很大一部分，这表明这些群体之间可能存在尚未了解的重要机制差异。
Identifying the specific genetic characteristics of successfully transmitted variants may prove central to the development of effective vaccine and microbicide interventions. Although human immunodeficiency virus transmission is associated with a population bottleneck, the extent to which different factors influence the diversity of transmitted viruses is unclear. We estimate here the number of transmitted variants in 69 heterosexual men and women with primary subtype C infections. From 1,505 env sequences obtained using a single genome amplification approach we show that 78% of infections involved single variant transmission and 22% involved multiple variant transmissions (median of 3). We found evidence for mutations selected for cytotoxic-T-lymphocyte or antibody escape and a high prevalence of recombination in individuals infected with multiple variants representing another potential escape pathway in these individuals. In a combined analysis of 171 subtype B and C transmission events, we found that infection with more than one variant does not follow a Poisson distribution, indicating that transmission of individual virions cannot be seen as independent events, each occurring with low probability. While most transmissions resulted from a single infectious unit, multiple variant transmissions represent a significant fraction of transmission events, suggesting that there may be important mechanistic differences between these groups that are not yet understood.