The L1 major capsid protein of HPV16 differentially modulates APC trafficking according to the vaccination or natural infection context.

in European Journal of Immunology (2010), 40(11), 3075-84

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The progression of cervical lesions suggests that viral antigens are not adequately ... [more ▼]

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The progression of cervical lesions suggests that viral antigens are not adequately presented to the immune system. The aim of this study was to determine whether HPV16 viral particles can influence the trafficking of human DC/Langerhans cells (LC), either by direct interactions with DC or following incubation with human normal keratinocytes that are in close contact with LC in the squamous epithelium. We first demonstrated that HPV16 L1 major capsid protein, when self-assembled into virus-like particles (VLP), is able to induce in DC an over-expression of CXC receptor 4 (CXCR4) via the activation of the NF-kappaB signaling pathway and to enhance DC motility in the presence of CXCL12, suggesting an ability to migrate towards lymph nodes. We also showed that conditioned media of HPV16 VLP-treated keratinocytes induce a lower LC migration than those from untreated keratinocytes and that prostaglandin E2 (PGE(2)), detected in HPV16 VLP-treated keratinocyte supernatants, may reduce LC recruitment into the squamous epithelium. Taken together, our data demonstrate that HPV16 VLP may differentially regulate the immune protective response according to their target cells. [less ▲]

High expression of PGE2 enzymatic pathways in cervical (pre)neoplastic lesions and functional consequences for antigen-presenting cells

in Cancer Immunology, Immunotherapy (2009), 58(4), 603-614

Silencing of E7 oncogene restores functional E-cadherin expression in human papillomavirus 16-transformed keratinocytes

in Carcinogenesis (2008), 29(7), 1441-7

Occult Herpes Simplex Virus Colonization of Bullous Dermatitides

in American Journal of Clinical Dermatology (2008)

Background: Acantholytic disorders, including pemphigus vulgaris, chronic benign familial pemphigus (Hailey-Hailey disease), Darier disease, and Grover transient acantholytic dermatosis, as well as other ... [more ▼]

Background: Acantholytic disorders, including pemphigus vulgaris, chronic benign familial pemphigus (Hailey-Hailey disease), Darier disease, and Grover transient acantholytic dermatosis, as well as other vesiculobullous disorders, including bullous pemphigoid, epidermolysis bullosa, and atopic dermatitis, are prone to florid infections by herpes simplex virus (HSV)-I and -II, and, more rarely, by varicella-zoster virus (VZV). As these infections are difficult to recognize clinically and histologically, their frequency remains unknown. A possible occult viral colonization has never been documented in these disorders. The manner in which the primary bullous disorders are contaminated by herpesviridae remains unclear. Objective: To retrospectivally assess the possible presence of HSV and VZV in a series of biopsies of acantholytic disorders and bullous pemphigoid. Method: The typical a-herpesviridae-related cytopathic signs were searched for by conventional microscopy in skin biopsies of patients with pemphigus vulgaris (n = 19), bullous pemphigoid (n = 20), Darier disease (n = 18), Hailey-Hailey disease((Author: is this the same as superficial pemphigus, as mentioned in both Histology sections?)) (n = 3), and Grover transient acantholytic dermatosis (n = 3). Immunohistochemistry (IHC) targeted specific HSV-I, HSV-II, and VZV antigens. Polymerase chain reaction (PCR) was used for detecting HSV- and VZV-specific DNA sequences. Results: No cytopathic signs suggestive of HSV or VZV infection were detected. However, IHC revealed HSV antigens in Darier disease (1/18, HSV-I), Grover transient acantholytic dermatosis (1/3, HSV-I), pemphigus vulgaris (1/20((Author: 1/19 in the Immunohistochemistry section?)), HSV-I), and bullous pemphigoid (2/ 20, HSV-I and HSV-II). In these IHC-positive cases, PCR amplified specific HSV primers in Darier disease (1/ 18), pemphigus vulgaris (1/20((Author: 1/19 in the PCR section?))), and bullous pemphigoid (1/20). VZV antigens and nucleic acids were never identified. The HSV antigens were ((Author: nearly always, as in the Immunohistochemistry section?)) restricted to the upper part of the granular layer and thus differed from the usual HSV distribution during cutaneous infection. Negative and positive controls yielded consistently positive and negative results, respectively.((Author: OK?)) Conclusion: This report shows for the first time that clinically and histologically occult HSV colonization may occur in Darier disease, Grover transient acantholytic disease, pemphigus vulgaris, and bullous pemphigoid. Given the frequent use of immunosuppressive treatments for primary bullous disorders, greater awareness of HSV colonization and infection is recommended in these patients. [less ▲]

Role of hormone cofactors in the human papillomavirus-induced carcinogenesis of the uterine cervix

in Molecular & Cellular Endocrinology (2007), 264(1-2), 1-5

If human papillomavirus (HPV) is necessary for the development of (pre)neoplastic lesions of the uterine cervix, it is not sufficient. Among the cofactors involved in the malignant transformation of cells ... [more ▼]

If human papillomavirus (HPV) is necessary for the development of (pre)neoplastic lesions of the uterine cervix, it is not sufficient. Among the cofactors involved in the malignant transformation of cells infected by HPV, sex hormones may facilitate the cervical carcinogenesis by different mechanisms, including the induction of squamous metaplasia in the transformation zone of the cervix, interactions between steroid hormones and HPV gene expression and alterations of the local immune microenvironment. [less ▲]