Human Papillomavirus Type 11 Alters the Transcription and Expression of Loricrin, the Major Cell Envelope Protein

Lehr, Elizabeth; Jarnik, Michael; Brown, Darron R.

doi:10.1006/viro.2002.1445

Cited by 16 publications

(11 citation statements)

References 23 publications

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“…However, SPR3 transcription was only slightly increased in RNA from HPV 59-infected epithelium. Loricrin amplimers were decreased from uninfected epithelium in both HPV 11-and 59-infected epithelium as previously found [Brown and Bryan, 2000;Lehr et al, 2002]. Scanning densitometry data points (adjusted for b-actin) were plotted against the cycle number for SPR2A, SPR2B, SPR3, and loricrin ( Fig.…”

Section: Hpv Infection Results In Abnormal Spr Transcriptionsupporting

confidence: 66%

“…It is possible that the abnormalities of loricrin and SPR expression could contribute to the altered mechanical properties seen in CCEs previously isolated from HPV-infected epithelium. CCEs from healthy human genital epithelium are approximately 65-70% loricrin [Steven and Steinert, 1994], and the thinner wall of the CCE from HPV-infected epithelium may be due to reduced expression of this protein, which provides only 26% of the CCE protein mass in HPV 11-infected epithelium [Lehr et al, 2002]. This cytopathic effect could render the CCE more likely to rupture from mechanical stress, thus releasing mature virions.…”

Section: Production Of Infectious Virions Occurs In Differentiated Kementioning

confidence: 99%

“…Our prior work shows that several CCE proteins are abnormal in abundance and distribution in both HPV 11-and HPV 59-infected epithelium. Loricrin is reduced in both HPV 11-and 59-infected genital epithelium, due to reduced transcription of the loricrin gene [Brown and Bryan, 2000;Lehr et al, 2002;Lehr and Brown, 2003]. Because mature HPV virions must escape from the desquamated keratinocyte, we have focused our studies on the CCE to determine a mechanism for viral release.…”

Section: Introductionmentioning

confidence: 99%

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Infection with human papillomavirus alters expression of the small proline rich proteins 2 and 3

Lehr¹,

Hohl²,

Huber³

et al. 2004

Journal of Medical Virology

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Human papillomavirus (HPV) does not induce lysis of infected keratinocytes, and the exact mechanisms of viral escape are not known. As keratinocytes differentiate, the cornified cell envelope (CCE) develops, providing a protective barrier to the host. Our prior studies have identified abnormalities in CCEs isolated from genital epithelium infected with HPV 11 (a low-risk HPV type) and HPV 59 (a high-risk HPV type). These abnormalities included reduced thickness and increased fragility compared to CCEs in healthy epithelium. Transcription of loricrin is also reduced in HPV 11- and 59-infected epithelium. In this study, uninfected and HPV 11- or 59-infected human genital epithelium were examined for expression of the small proline rich proteins (SPRs), which serve as cross-linking proteins within the CCE. Limiting cycle RT-PCR was performed to detect the various SPR transcripts in HPV 11- and 59-infected, or uninfected epithelium. Immunohistochemical analysis and immunoblot assays were performed to analyze the distribution and quantity of SPR2A, SPR2B, and SPR3. SPR2B transcripts were moderately increased in the HPV 11- and 59-infected tissues and SPR3 transcripts were significantly increased in HPV 11-infected tissues and minimally increased in HPV 59-infected tissues. SPR2B protein quantities were moderately increased while SPR2A was not significantly changed. SPR3 protein, while not present in uninfected epithelium, was detected in abundance in HPV 11-infected tissue. We conclude that low-risk and high-risk HPVs share the ability to alter expression of CCE proteins, although the exact mechanisms may differ. Expression of individual SPRs differed between these types and these alterations may play a role in fragility of CCEs in HPV infection.

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Section: Hpv Infection Results In Abnormal Spr Transcriptionsupporting

confidence: 66%

Section: Production Of Infectious Virions Occurs In Differentiated Kementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Infection with human papillomavirus alters expression of the small proline rich proteins 2 and 3

Lehr¹,

Hohl²,

Huber³

et al. 2004

Journal of Medical Virology

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“…The E6 and E7 genes of both HPV-20 and HPV-27 seem to influence these pathways, as the expressions of these differentiation markers in the nontransgenic mice, which were irradiated in the same way, were not similarly modified. A link between both involucrin and loricrin expression and the late viral proteins of a number of HPV types has been reported (34,40,47), but the role of the early proteins of the papillomaviruses is unknown.…”

Section: Discussionmentioning

confidence: 99%

E6/E7 Expression of Human Papillomavirus Type 20 (HPV-20) and HPV-27 Influences Proliferation and Differentiation of the Skin in UV-Irradiated SKH-hr1 Transgenic Mice

Michel

Kopp‐Schneider

Zentgraf

et al. 2006

J Virol

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The functional role of UV irradiation, in combination with the E6 and E7 proteins of the cutaneous human papillomavirus (HPV) types in the malignant conversion of benign papillomatous lesions, has not been elucidated. Transgenic SKH-hr1 hairless mice expressing HPV-20 and HPV-27 E6 and E7 proteins in the suprabasal compartment were generated and exposed to chronic UV irradiation. UV irradiation is a major etiological factor in the development of nonmelanoma skin cancer, one of the most frequent cancers occurring among the Caucasian population worldwide (6, 38). These basal cell and squamous cell carcinomas (SCC) occur primarily on sun-exposed sites. Wild-type p53 protein is expressed at increased levels after UV irradiation, thereby shutting off DNA synthesis and cell replication and allowing for DNA repair and maintenance of genetic integrity after DNA damage. Severe UV irradiation induces not only acute inflammatory reactions but also DNA damage, which is reflected in the induction of p53 mutations (5,36,39,43,57). These p53 mutations are distributed as scattered cells or in clusters of p53-immunoreactive keratinocytes (4, 35).Papillomavirus infections have been implicated in the etiology of nonmelanoma skin cancer both in immunocompetent and in immunosuppressed individuals. This is evidenced in the malignant conversion of 30% to 60% of warts occurring on sun-exposed body sites in patients with the immune-impairing disease Epidermodysplasia verruciformis (37). Human papillomavirus (HPV) DNA has been demonstrated in the majority of premalignant lesions and SCC of the skin (12,21,23,52). The mechanism by which the high-risk mucosal HPV types participate in anogenital carcinogenesis has been elucidated. The expression of the E6 and E7 genes of the high-risk mucosal HPV types stimulates proliferation and is a precondition for immortalization and malignant growth (58, 59). Very little is known about the molecular pathways involved after infection with cutaneous papillomavirus types. The proinflammatory cytokines (interleukin-1␣ [IL-1␣], IL-1␤, IL-6, and IL-17 and alpha, beta, and gamma interferons) induced by UV irradiation either induce or inhibit the promoters of a number of HPV types associated with cutaneous lesions (13,14,48). The E6 proteins of certain cutaneous HPV types are unable to promote p53 degradation in vitro (18, 51, 53) but effectively inhibit UV-induced apoptosis by attenuating the transcription of p53-regulated proapoptotic genes as well as stimulating the degradation of the proapoptotic protein Bak (26). The ability of the E7 protein of cutaneous HPV types to bind to the pocket protein Rb is not a determinant for oncogenicity for the cutaneous HPV types tested as it has been demonstrated for the high-risk mucosal HPV types (8,58).A number of in vivo models using transgenic mice have been reported in which the E6 and E7 properties of high-risk mucosal HPV-16 or HPV-18 have been studied. Tumors developed in different organs, independent of the promoter used for expression (1,2,7,22,29,33). The in ...

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“…RNA was isolated from individual plates of cells at 24 h intervals using the RNeasy Kit (Qiagen). RT-PCR analysis was then performed as previously de-scribed [12] to detect transcripts encoding loricrin, the major CCE protein [13].…”

Section: Expression Of E1ˆe4 In Differentiated Niks Cellsmentioning

confidence: 99%

Intracellular Expression Patterns of the Human Papillomavirus Type 59 E1^E4 Protein in COS Cells, Keratinocytes, and Genital Epithelium

Brown

Brown²,

Lehr³

2004

Intervirology

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Objective: To compare and contrast the intracellular distribution pattern of the human papillomavirus type 59 (HPV 59) E1^E4 protein in COS cells, human keratinocytes, and naturally infected genital epithelium. Methods: The HPV 59 E1^E4 protein was expressed in COS cells and NIKS cells (immortalized human keratinocytes). A subset of NIKS cells was induced to differentiate. The intracellular distribution pattern of E1^E4 and the effects of E1^E4 expression on the cytoskeleton network were compared for COS and NIKS cells. Expression of E1^E4 was examined in HPV 59-infected foreskin xenografts grown in athymic mice and in a natural HPV 59-infected genital lesion. Results: The HPV 59 E1^E4 protein formed dense perinuclear inclusions in COS cells, similar to those reported for the HPV 16 E1^E4 protein. In contrast, the E1^E4 protein was diffusely cytoplasmic in undifferentiated NIKS cells, co-localizing with an intact cytokeratin filament network. The E1^E4 protein was concentrated in the region of the cornified cell envelope (CCE) of differentiated NIKS cells, co-localizing with involucrin, a CCE component. A similar distribution in the region of the CCE was observed for E1^E4 protein in HPV 59-infected human epithelial tissues. Conclusions: The HPV 59 E1^E4 protein is cytoplasmic and co-localizes with an intact cytokeratin filament network in undifferentiated keratinocytes. The E1^E4 protein is distributed in the region of the CCE and co-localizes with involucrin in differentiated human keratinocytes, consistent with the intracellular distribution pattern observed in HPV 59-infected epithelium.

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Human Papillomavirus Type 11 Alters the Transcription and Expression of Loricrin, the Major Cell Envelope Protein

Cited by 16 publications

References 23 publications

Infection with human papillomavirus alters expression of the small proline rich proteins 2 and 3

Infection with human papillomavirus alters expression of the small proline rich proteins 2 and 3

E6/E7 Expression of Human Papillomavirus Type 20 (HPV-20) and HPV-27 Influences Proliferation and Differentiation of the Skin in UV-Irradiated SKH-hr1 Transgenic Mice

Intracellular Expression Patterns of the Human Papillomavirus Type 59 E1^E4 Protein in COS Cells, Keratinocytes, and Genital Epithelium

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