Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, TN, United States; LeBonheur Children's Hospital, Memphis, TN, United States; Children's Foundation Research Center, Memphis, TN, United States.
Department of Pediatrics, University of Tennessee Health Sciences Center, Memphis, TN, United States.
J Clin Virol. 2018 Sep;106:1-6. doi: 10.1016/j.jcv.2018.06.014. Epub 2018 Jun 27.
Respiratory symptoms in RSV persist long after the virus is no longer detected by culture. Current concepts of RSV pathogenesis explain this by RSV inducing a long-lasting pathogenic immune cascade. We alternatively hypothesized that prolonged unrecognized RSV replication may be responsible and studied this possibility directly in a human wild-type RSV experimental infection model.
The objective of the current report was to define the duration of true human RSV replication by studying it directly in immunocompetent adults experimentally infected with a clinical strain of RSV utilizing this previously established safe and reproducible model.
35 healthy adult volunteers were inoculated with RSV-A (Memphis-37, a low11 passage clinical strain virus, manufactured from a hospitalized bronchiolitic infant) and evaluated over 12 days. Viral load by culture, parallel quantitative PCR (genomic, message) and RSV-specific IgA, were measured twice daily from serially collected nasal washes.
After inoculation, 77% (27/35) of volunteers became RSV infected. As expected, culture-detectable RSV ceased abruptly by the 5-6 t h 15 infection day. However, infected volunteers demonstrated prolonged RSV presence by both genomic and message PCR. RSV-specific IgA rose within respiratory secretions of infected volunteers during same time frame.
RSV replication appears to continue in humans far longer than previously thought. The rise in nasal RSV-specific IgA shortly after infection likely neutralizes culture detectable virus producing misleadingly short durations of infection. Prolonged viral replication helps explain RSV's extended disease manifestations and increases the potential utility of antivirals.
呼吸道合胞病毒（RSV）感染后，即使病毒在培养中不再被检测到，呼吸道症状仍会持续很长时间。目前关于 RSV 发病机制的概念通过 RSV 诱导持久的致病性免疫级联反应来解释这一现象。我们则假设，持续未被识别的 RSV 复制可能是导致这一现象的原因，并在人类野生型 RSV 实验感染模型中直接研究了这种可能性。
本研究旨在通过利用先前建立的安全且可重复的模型，直接在免疫功能正常的成人中研究 RSV 实验感染，从而明确 RSV 真正复制的持续时间。
35 名健康成年志愿者接种 RSV-A（Memphis-37，一种低传代临床分离株病毒，由住院毛细支气管炎婴儿制造），并在 12 天内进行评估。通过培养、平行定量 PCR（基因组、mRNA）和 RSV 特异性 IgA 对病毒载量进行检测，从连续采集的鼻洗液中进行每日两次的测量。
接种后，77%（27/35）的志愿者发生 RSV 感染。如预期的那样，培养可检测到的 RSV 在第 5-6 天感染时突然停止。然而，受感染的志愿者通过基因组和 mRNA PCR 显示出 RSV 的持续存在。RSV 特异性 IgA 在感染志愿者的呼吸道分泌物中也在同一时间范围内升高。
RSV 复制似乎在人类中持续时间比以前认为的要长得多。感染后短时间内鼻腔 RSV 特异性 IgA 的升高可能中和了可培养检测到的病毒，导致感染时间的假象缩短。病毒复制时间延长有助于解释 RSV 延长的疾病表现，并增加抗病毒药物的潜在应用。
