Human <i>Beta‐papillomavirus</i> infection and keratinocyte carcinomas

Quint, Koen D.; Genders, Roel E.; Koning, Maurits N.C. de; Borgogna, Cinzia; Gariglio, Marisa; Bavinck, Jan Nico Bouwes; Doorbar, John; Feltkamp, Mariet C.W.

doi:10.1002/path.4425

Cited by 115 publications

(135 citation statements)

References 121 publications

(147 reference statements)

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…There is strong evidence from laboratory studies to suggest that HPV plays a role in cSCC carcinogenesis, principally through synergy with UVR 13, 14, 15. In normal cells, UVR upregulates cellular defense processes leading to p53 activation, cell cycle arrest, apoptosis, or DNA repair.…”

Section: Discussionmentioning

confidence: 99%

“…αHPVs (eg, mucosal HPV types 16 and 18) are responsible for the development of cervical carcinoma and other mucosal SCCs, including anogenital and oropharyngeal carcinomas 10. The role of skin βPVs in cSCC carcinogenesis is controversial,9, 11, 12 but evidence for etiologic involvement is accumulating 13, 14, 15, 16, 17. βPV cause latent, persistent skin infections18 and were first discovered in cSCCs from patients with epidermodysplasia verruciformis, a rare genetic skin disease characterized by increased susceptibility to βPV with a high risk of cSCC on sun‐exposed skin 9…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study

Bavinck

Feltkamp

Green

et al. 2018

American Journal of Transplantation

View full text Add to dashboard Cite

Organ transplant recipients (OTRs) have a 100‐fold increased risk of cutaneous squamous cell carcinoma (cSCC). We prospectively evaluated the association between β genus human papillomaviruses (βPV) and keratinocyte carcinoma in OTRs. Two OTR cohorts without cSCC were assembled: cohort 1 was transplanted in 2003‐2006 (n = 274) and cohort 2 was transplanted in 1986‐2002 (n = 352). Participants were followed until death or cessation of follow‐up in 2016. βPV infection was assessed in eyebrow hair by using polymerase chain reaction–based methods. βPV IgG seroresponses were determined with multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of βPV by using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HRs). OTRs with 5 or more different βPV types in eyebrow hair had 1.7 times the risk of cSCC vs OTRs with 0 to 4 different types (HR 1.7, 95% confidence interval 1.1‐2.6). A similar risk was seen with high βPV loads (HR 1.8, 95% confidence interval 1.2‐2.8). No significant associations were seen between serum antibodies and cSCC or between βPV and basal cell carcinoma. The diversity and load of βPV types in eyebrow hair are associated with cSCC risk in OTRs, providing evidence that βPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study

Bavinck

Feltkamp

Green

et al. 2018

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…On the basis of biologic and epidemiologic data, some HPV types within the beta-1 and beta-2 species are likely to be involved, together with UV irradiation, in the development of NMSC (2,3,22). However, very little is known about the biology of most beta HPV types and whether they are linked to additional human diseases.…”

Section: Discussionmentioning

confidence: 99%

Novel ß-HPV49 Transgenic Mouse Model of Upper Digestive Tract Cancer

et al. 2016

View full text Add to dashboard Cite

The beta genus of human papillomaviruses (ß-HPV) includes approximately 50 different viral types that are subdivided into five species (ß-1 through ß-5). Nonmelanoma cancers may involve some ß-1 and ß-2 HPV types, but the biology of most ß-HPV types and their possible connections to human disease are still little characterized. In this study, we studied the effects of ß-3 type HPV49 in a novel transgenic (Tg) mouse model, using a cytokeratin K14 promoter to drive expression of the E6 and E7 genes from this virus in the basal skin epidermis and the mucosal epithelia of the digestive tract (K14 HPV49 E6/E7-Tg mice). Viral oncogene expression only marginally increased cellular proliferation in the epidermis of Tg animals, compared with wild-type littermates, and we observed no spontaneous tumor formation during their entire lifespan. However, we found that K14 HPV49 E6/E7-Tg mice were highly susceptible to upper digestive tract carcinogenesis upon initiation with 4-nitroquinoline 1-oxide (4NQO). This was a selective effect, as the same mice did not exhibit any skin lesions after chronic UV irradiation. Opposite results were observed in an analogous Tg model expressing the ß-2 HPV38 E6 and E7 oncogenes at the same anatomic sites. While these mice were highly susceptible to UV-induced skin carcinogenesis, as previously shown, they were little affected by 4NQO treatment. Overall, our findings highlight important differences in the biologic properties of certain ß-type HPV that affect their impact on carcinogenesis in an anatomic site-specific manner.

show abstract

“…Human papillomaviruses (HPV) are small nonenveloped dsDNA viruses that selectively infect keratinocytes in stratified epithelia of both skin and mucosa (34,35). Like herpesviruses, they replicate in the nucleus, and their target cells-keratinocytes-constitutively express IFI16, endowing the cells with the ability to control HPV replication through IFI16 activity (23,36).…”

mentioning

confidence: 99%

The Nuclear DNA Sensor IFI16 Acts as a Restriction Factor for Human Papillomavirus Replication through Epigenetic Modifications of the Viral Promoters

Cigno

Andrea

Borgogna

et al. 2015

J Virol

Self Cite

View full text Add to dashboard Cite

The human interferon-inducible IFI16 protein, an innate immune sensor of intracellular DNA, was recently demonstrated to act as a restriction factor for human cytomegalovirus (HCMV) and herpes simplex virus 1 (HSV-1) infection by inhibiting both viral-DNA replication and transcription. Through the use of two distinct cellular models, this study provides strong evidence in support of the notion that IFI16 can also restrict human papillomavirus 18 (HPV18) replication. In the first model, an immortalized keratinocyte cell line (NIKS) was used, in which the IFI16 protein was knocked down through the use of small interfering RNA (siRNA) technology and overexpressed following transduction with the adenovirus IFI16 (AdVIFI16) vector. The second model consisted of U2OS cells transfected by electroporation with HPV18 minicircles. In differentiated IFI16-silenced NIKS-HPV18 cells, viral-load values were significantly increased compared with differentiated control cells. Consistent with this, IFI16 overexpression severely impaired HPV18 replication in both NIKS and U2OS cells, thus confirming its antiviral restriction activity. In addition to the inhibition of viral replication, IFI16 was also able to reduce viral transcription, as demonstrated by viralgene expression analysis in U2OS cells carrying episomal HPV18 minicircles and HeLa cells. We also provide evidence that IFI16 promotes the addition of heterochromatin marks and the reduction of euchromatin marks on viral chromatin at both early and late promoters, thus reducing both viral replication and transcription. Altogether, these results argue that IFI16 restricts chromatinized HPV DNA through epigenetic modifications and plays a broad surveillance role against viral DNA in the nucleus that is not restricted to herpesviruses. IMPORTANCEIntrinsic immunity is mediated by cellular restriction factors that are constitutively expressed and active even before a pathogen enters the cell. The host nuclear factor IFI16 acts as a sensor of foreign DNA and an antiviral restriction factor, as recently demonstrated by our group for human cytomegalovirus (HCMV) and herpes simplex virus 1 (HSV-1). Here, we provide the first evidence that IFI16 inhibits HPV18 replication by repressing viral-gene expression and replication. This antiviral restriction activity was observed in immortalized keratinocytes transfected with the religated genomes and in U2OS cells transfected with HPV18 minicircles, suggesting that it is not cell type specific. We also show that IFI16 promotes the assembly of heterochromatin on HPV DNA. These changes in viral chromatin structure lead to the generation of a repressive state at both early and late HPV18 promoters, thus implicating the protein in the epigenetic regulation of HPV gene expression and replication. Many recent studies point to the importance of cell-type-and host-specific expression of antiviral factors in limiting viral infection (1-4). Some of the very early antiviral responses include the activation of intrinsic restriction factors at h...

show abstract

Human Beta‐papillomavirus infection and keratinocyte carcinomas

Cited by 115 publications

References 121 publications

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study

Novel ß-HPV49 Transgenic Mouse Model of Upper Digestive Tract Cancer

The Nuclear DNA Sensor IFI16 Acts as a Restriction Factor for Human Papillomavirus Replication through Epigenetic Modifications of the Viral Promoters

Contact Info

Product

Resources

About