疣、低丙种球蛋白血症、感染和骨髓缺乏症 (WHIM) 综合征是一种罕见的人类原发性免疫缺陷疾病，由 CXCR4 功能获得引起，主要是由于 CXCR4 的遗传性杂合突变所致。 WHIM 患者的一项主要临床症状是他们对人乳头瘤病毒 (HPV) 诱发的疾病（例如疣）高度敏感。持续的高危 HPV 感染导致 5% 的人类癌症，包括宫颈癌、肛门生殖器癌、头颈癌和一些皮肤癌。携带与 WHIM 患者相同的突变的 WHIM 小鼠被创建，以研究 WHIM 综合征患者出现症状的根本原因。使用鼠乳头瘤病毒 (MmuPV1) 作为小鼠 HPV 诱导疾病的感染模型，我们证明与野生型小鼠相比，WHIM 小鼠更容易受到 MmuPV1 诱导的疣（乳头状瘤）的影响。也就是说，当小鼠暴露于低剂量的 MmuPV1 时，与野生型小鼠相比，WHIM 小鼠的乳头状瘤发病率更高。 MmuPV1 感染促进了野生型小鼠血液中骨髓细胞和淋巴细胞的动员，但在 WHIM 小鼠中则不然。 WHIM 小鼠中乳头状瘤的较高发病率和较大尺寸与乳头状瘤内浸润性 T 细胞丰度较低相关。最后，我们证明将野生型小鼠的骨髓移植到 WHIM 小鼠中可以使乳头状瘤的发生率和大小正常化，这与造血细胞中的 WHIM 突变导致 WHIM 小鼠对 MmuPV1 诱导的疾病具有更高的易感性一致。我们的结果证明 WHIM 小鼠的 MmuPV1 感染是一种强大的临床前感染模型，可用于研究减轻 WHIM 综合征中乳头瘤病毒感染的治疗方案。版权所有：© 2024 Wang 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome is a rare primary immunodeficiency disease in humans caused by a gain of function in CXCR4, mostly due to inherited heterozygous mutations in CXCR4. One major clinical symptom of WHIM patients is their high susceptibility to human papillomavirus (HPV) induced disease, such as warts. Persistent high risk HPV infections cause 5% of all human cancers, including cervical, anogenital, head and neck and some skin cancers. WHIM mice bearing the same mutation identified in WHIM patients were created to study the underlying causes for the symptoms manifest in patients suffering from the WHIM syndrome. Using murine papillomavirus (MmuPV1) as an infection model in mice for HPV-induced disease, we demonstrate that WHIM mice are more susceptible to MmuPV1-induced warts (papillomas) compared to wild type mice. Namely, the incidence of papillomas is higher in WHIM mice compared to wild type mice when mice are exposed to low doses of MmuPV1. MmuPV1 infection facilitated both myeloid and lymphoid cell mobilization in the blood of wild type mice but not in WHIM mice. Higher incidence and larger size of papillomas in WHIM mice correlated with lower abundance of infiltrating T cells within the papillomas. Finally, we demonstrate that transplantation of bone marrow from wild type mice into WHIM mice normalized the incidence and size of papillomas, consistent with the WHIM mutation in hematopoietic cells contributing to higher susceptibility of WHIM mice to MmuPV1-induced disease. Our results provide evidence that MmuPV1 infection in WHIM mice is a powerful preclinical infectious model to investigate treatment options for alleviating papillomavirus infections in WHIM syndrome.Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.