Data from: Increased susceptibility of WHIM mice to Papillomavirus-induced disease is dependent upon immune cell dysfunction

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.