AI Article Synopsis

  • - WHIM syndrome is a rare genetic immunodeficiency caused by inherited mutations in the CXCR4 gene, leading to increased risk of HPV-related diseases like warts and various cancers.
  • - Studies using WHIM mice, which mimic the syndrome in humans, reveal they are more vulnerable to HPV-induced warts, showing a higher incidence of papillomas than normal mice when exposed to low doses of the virus.
  • - Transplanting bone marrow from healthy mice into WHIM mice reduces the size and frequency of warts, indicating that the immune system's malfunction in WHIM syndrome contributes to their susceptibility to papillomavirus infections.

Article Abstract

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11398641PMC
http://dx.doi.org/10.1371/journal.ppat.1012472DOI Listing

Publication Analysis

Top Keywords

wild type
16
type mice
16
mice
15
mmupv1 infection
12
mice mice
12
susceptibility mice
8
compared wild
8
size papillomas
8
disease
5
papillomas
5

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!