Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
PLoS One. 2018 Mar 27;13(3):e0194837. doi: 10.1371/journal.pone.0194837. eCollection 2018.
Penile acquisition of HIV infection contributes substantially to the global epidemic. Our goal was to establish a preclinical macaque model of penile HIV infection for evaluating the efficacy of new HIV prevention modalities. Rhesus macaques were challenged once or twice weekly with consistent doses of SHIVsf162P3 (a chimeric simian-human immunodeficiency virus containing HIV env) ranging from 4-600 TCID50 (50% tissue culture infective dose), via two penile routes, until systemic SHIV infection was confirmed. One route exposed the inner foreskin, glans and urethral os to virus following deposition into the prepuce (foreskin) pouch. The second route introduced the virus non-traumatically into the distal urethra only. Single-route challenges resulted in dose-dependent rates of SHIV acquisition informing selection of optimal SHIV dosing. Concurrent SHIV challenges via the prepuce pouch (200 TCID50) and urethra (16 TCID50) resulted in infection of 100% (10/10) animals following a median of 2.5 virus exposures (range, 1-12). We describe the first rhesus macaque repeat-exposure SHIV challenge model of penile HIV acquisition. Utilization of the model should further our understanding of penile HIV infection and facilitate the development of new HIV prevention strategies for men.
阴茎获得性 HIV 感染在全球流行中起着重要作用。我们的目标是建立一种猕猴阴茎 HIV 感染的临床前模型，以评估新的 HIV 预防方法的疗效。恒河猴每周接受一次或两次挑战，给予一致剂量的 SHIVsf162P3（一种嵌合猴-人免疫缺陷病毒，含有 HIV env），范围从 4-600TCID50（50%组织培养感染剂量），通过两种阴茎途径，直到确认系统性 SHIV 感染。一种途径是将病毒注入阴茎包皮（包皮）袋内，暴露内包皮、龟头和尿道口，以感染病毒。第二种途径是非创伤性地将病毒引入仅远端尿道。单途径挑战导致 SHIV 获得的剂量依赖性比率，从而选择最佳 SHIV 剂量。通过包皮袋（200TCID50）和尿道（16TCID50）同时进行 SHIV 挑战，在中位数为 2.5 次病毒暴露（范围为 1-12 次）后，导致 100%（10/10）动物感染。我们描述了第一个恒河猴重复暴露 SHIV 挑战阴茎 HIV 获得模型。该模型的使用将有助于我们更好地了解阴茎 HIV 感染，并促进为男性开发新的 HIV 预防策略。
