Sigmovir Biosystems, Inc., 9610 Medical Center Drive, Suite 100, Rockville, MD 20850, USA.
Center for Vaccines and Immunology, Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Viruses. 2023 Feb 9;15(2):476. doi: 10.3390/v15020476.
Human metapneumovirus (hMPV) is an important cause of respiratory disease in immunocompromised individuals, yet hMPV infection has not been modeled before in immunocompromised animals. In this work, cotton rats immunosuppressed by cyclophosphamide were infected with hMPV, and viral replication and pulmonary inflammation in these animals were compared to those in normal hMPV-infected . The efficacy of prophylactic and therapeutic administration of the anti-hMPV antibody MPV467 was also evaluated. Immunosuppressed animals had higher pulmonary and nasal titers of hMPV on day 5 post-infection compared to normal animals, and large amounts of hMPV were still present in the respiratory tract of immunosuppressed animals on days 7 and 9 post-infection, indicating prolonged viral replication. Immunosuppression was accompanied by reduced pulmonary histopathology in hMPV-infected cotton rats compared to normal animals; however, a delayed increase in pathology and pulmonary chemokine expression was seen in immunosuppressed cotton rats. Prophylactic and therapeutic MPV467 treatments protected both upper and lower respiratory tracts against hMPV infection. The lung pathology and pulmonary expression of IP-10 and MIP-1α mRNA were reduced by therapeutic MPV467 administration. These results indicate that immunosuppressed cotton rats represent a useful model for studying hMPV pathogenesis and for evaluating therapeutics that could alleviate hMPV-induced disease in immunocompromised subjects.
人偏肺病毒（hMPV）是免疫功能低下个体呼吸道疾病的重要病因，但以前尚未在免疫功能低下动物中建立 hMPV 感染模型。在这项工作中，用环磷酰胺免疫抑制的棉鼠感染 hMPV，并比较这些动物与正常 hMPV 感染动物的病毒复制和肺部炎症。还评估了抗 hMPV 抗体 MPV467 的预防和治疗给药的效果。与正常动物相比，感染后第 5 天免疫抑制动物的肺部和鼻腔 hMPV 滴度更高，感染后第 7 和第 9 天免疫抑制动物的呼吸道仍存在大量 hMPV，表明病毒复制延长。与正常动物相比，感染 hMPV 的棉鼠的肺部组织病理学在免疫抑制时减少；然而，在免疫抑制棉鼠中观察到病理学和肺部趋化因子表达的延迟增加。预防性和治疗性 MPV467 治疗可预防 hMPV 感染上、下呼吸道。治疗性 MPV467 给药可降低肺部病理学和 IP-10 和 MIP-1α mRNA 的肺部表达。这些结果表明，免疫抑制棉鼠代表了研究 hMPV 发病机制和评估可减轻免疫功能低下宿主中 hMPV 诱导疾病的治疗方法的有用模型。
