University of California, San Diego, La Jolla, California, USA.
J Virol. 2013 Dec;87(23):12737-44. doi: 10.1128/JVI.02260-13. Epub 2013 Sep 18.
Investigating the incidence and prevalence of HIV-1 superinfection is challenging due to the complex dynamics of two infecting strains. The superinfecting strain can replace the initial strain, be transiently expressed, or persist along with the initial strain in distinct or in recombined forms. Various selective pressures influence these alternative scenarios in different HIV-1 coding regions. We hypothesized that the potency of the neutralizing antibody (NAb) response to autologous viruses would modulate viral dynamics in env following superinfection in a limited set of superinfection cases. HIV-1 env pyrosequencing data were generated from blood plasma collected from 7 individuals with evidence of superinfection. Viral variants within each patient were screened for recombination, and viral dynamics were evaluated using nucleotide diversity. NAb responses to autologous viruses were evaluated before and after superinfection. In 4 individuals, the superinfecting strain replaced the original strain. In 2 individuals, both initial and superinfecting strains continued to cocirculate. In the final individual, the surviving lineage was the product of interstrain recombination. NAb responses to autologous viruses that were detected within the first 2 years of HIV-1 infection were weak or absent for 6 of the 7 recently infected individuals at the time of and shortly following superinfection. These 6 individuals had detectable on-going viral replication of distinct superinfecting virus in the env coding region. In the remaining case, there was an early and strong autologous NAb response, which was associated with extensive recombination in env between initial and superinfecting strains. This extensive recombination made superinfection more difficult to identify and may explain why the detection of superinfection has typically been associated with low autologous NAb titers.
研究 HIV-1 再次感染的发生率和流行率具有挑战性，因为两种感染毒株的复杂动力学。再次感染的毒株可以取代初始毒株，可以短暂表达，也可以以不同或重组的形式与初始毒株共存。不同的选择压力会影响不同 HIV-1 编码区域的这些替代情况。我们假设，针对自身病毒的中和抗体 (NAb) 反应的效力将在有限的再次感染病例中调节 env 中的病毒动力学。从 7 名有再次感染证据的个体的血浆中生成了 HIV-1 env 焦磷酸测序数据。对每个患者内的病毒变异体进行重组筛选，并使用核苷酸多样性评估病毒动力学。在再次感染之前和之后评估对自身病毒的 NAb 反应。在 4 名个体中，再次感染的毒株取代了原始毒株。在 2 名个体中，初始和再次感染的毒株继续共同循环。在最后一名个体中，存活的谱系是种间重组的产物。在 HIV-1 感染的前 2 年内检测到的针对自身病毒的 NAb 反应在再次感染时和之后不久，7 名最近感染的个体中的 6 名个体较弱或不存在。这 6 名个体在 env 编码区检测到持续进行的不同再次感染病毒的复制。在剩下的病例中，存在早期且强烈的自身 NAb 反应，这与初始和再次感染的毒株之间 env 中的广泛重组有关。这种广泛的重组使得再次感染更难识别，这可能解释了为什么再次感染的检测通常与低自身 NAb 滴度相关。
