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Objectives Aim of this retrospective study was to analyze the dynamics of BKPyV reactivation in allogeneic hematopoietic stem cell transplant recipients in order to identify patients with higher risk to develop BKPyV-associated hemorrhagic cystitis ( BKPyV-associated HC). Methods The study included 58 allo- HSCT recipients from the University Hospital of Cologne detected BKPyV positive by real-time PCR between 2009 and 2015. For correlative analysis, the first detected BKPyV- DNA load in urine and in plasma as well as the onset and severity of HC following the first day of conditioning regimen was considered. Phylogenetic analysis of BKPyV isolates was performed. Results In 25 of 58 patients, BKPyV- DNA was detected in urine only (group U), whereas 33 patients developed additional viremia (group P). A chronologic sequence viruria-viremia- HC was identified. Viral load of >106 copies/ mL at first viruria and evidence of viremia after 45 days from the start of conditioning represented risk factors for the onset of HC. Molecular characterization revealed a non-stereotypic distribution of viral subtypes across groups U and P. Conclusions Monitoring of BKPyV- DNA by real-time PCR after initiation of conditioning, regularly performed in clinical practice, can be a crucial tool for the early identification of patients with higher risk of BKPyV-associated HC. [ABSTRACT FROM AUTHOR]

The evolution of hepatitis-B virus (HBV) drug resistance is characterized by the emergence of resistance conferring mutations and compensatory mutations. Therefore HBV drug-resistant isolates often harbor multiple mutations in the reverse transcriptase (RT) and corresponding mutations in the hepatitis B surface antigen (HBsAg). In this study mutational patterns of 60 HBV isolates harboring drug resistance mutations rtM204V or rtM204I were retrospectively analyzed. Both mutations, especially mutation rtM204V, were most often accompanied by compensatory mutations rtV173L and rtL180M but also by mutations conferring entecavir (n = 5) or adefovir resistance (n = 4). In addition, 22 (36.7%) drug resistant HBV isolates carried mutations related to immune escape in the HBsAg. In seven cases premature stop codons in HBsAg were detected resulting in the expression of truncated HBsAg. Clonal analysis of these seven quasispecies even disclosed the presence of HBV isolates carrying further stop codons and in one case the occurrence of resistance mutation rtA181T without the stop codon mutation sW172*. Interestingly, only one HBV clone carried the resistance mutations rtM204V and rtA181T. HBV drug resistant isolates frequently harbored HBsAg mutations associated with immune escape or disease progression pointing to a complex interaction of both proteins. HBV genotypic resistance tests based on population sequencing methods seemed to be inappropriate for determining the clinical relevance of stop codons in the HBsAg. J. Med. Virol. 85:775-779, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPV) have been associated with the development of non-melanoma skin cancer (NMSC) but the molecular mechanisms of the role of the virus in NMSC development are not clearly understood. Abnormal epithelial differentiation seen in malignant transformation of keratinocytes is associated with changes in keratin expression. The purpose of this study was to investigate the phenotype of primary human adult keratinocytes expressing early genes of HPV8 with specific reference to their differentiation and cell cycle profile to determine whether early genes of HPV8 lead to changes that are consistent with transformation. The expression of HPV8 early genes either individually or simultaneously caused distinct changes in the keratinocyte morphology and induced an abnormal keratin expression pattern, that included simple epithelial (K8, K18, K19), hyperproliferation-specific (K6, K16), basal-specific (K14, K15) and differentiation-specific (K1, K10) keratins. Our results indicate that expression of HPV8 early genes disrupts the normal keratin expression pattern in vitro. Expression of HPV8-E7 alone caused polyploidy that was associated with decreased expression of p21 and pRb. Expression of individual genes or in combination differentially influenced cell morphology and cell cycle distribution which might be important in HPV8-induced keratinocyte transformation. [ABSTRACT FROM AUTHOR]

Human papillomaviruses (HPV) are small DNA viruses that induce a wide variety of hyperproliferative lesions in cutaneous and mucosal epithelia. It is proposed that HPV is involved in non-melanoma skin cancer development. We have previously shown that HPV8 transgenic mice spontaneously develop papillomatous skin tumors. Histology revealed epidermal hyperplasia, acanthosis and hypergranulosis and in some cases squamous cell carcinomas (SCC). Zymographic and immunoblot analysis of normal skin extracts identified increased amounts of matrix metalloproteinase (MMP)-9, MMP-13 and MT1-MMP in HPV8-positive mice compared with HPV8-negative animals. In situ gelatin zymography of tumor specimens displayed a strong proteolytic activity in papillomas, and SCC putatively attributed to the increased amounts of activated MMP-9 found in tissue extracts. In addition, immunoblot analysis revealed increased amounts of active MMP-13 and MT1-MMP in tumor extracts as compared with control extracts. Immunohistochemical stainings of SCC specimens depicted MMP-13 to be specifically expressed in stromal fibroblasts neighboring the tumor islands, whereas MT1-MMP was detected both in tumor cells and in stromal cells. Taken together, these results implicate a role for MMPs in the development of HPV8-induced cutaneous tumors. [ABSTRACT FROM AUTHOR]

Presents a list of articles about modifications of keratinocyte functions by human papillomaviruses (HPV). "Pathogenesis of Human Papilloma Viruses in Differentiating Epithelia," by M. S. Longworth and L. A. Laimins; "The E6 and E7 Proteins of the Cutaneous Human Papilloma Virus Type 38 Display Transforming Properties," by S. Caldeira, I. Zehbe and R. Accardi; "The E7 Protein of Cutaneous Human Papilloma Virus Type 8 Causes Invasion of Human Keratinocytes Into the Dermis in Organotypic Cultures of Skin," by B. Akgül, R. Garcia-Escudero and L. Ghali.