Target Cell Cyclophilins Facilitate Human Papillomavirus Type 16 Infection

Following attachment to primary receptor heparan sulfate proteoglycans (HSPG), human papillomavirus type 16 (HPV16) particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB) facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV–induced diseases

Entry of Human Papillomavirus Type 16 by Actin-Dependent, Clathrin- and Lipid Raft-Independent Endocytosis

Infectious endocytosis of incoming human papillomavirus type 16 (HPV-16), the main etiological agent of cervical cancer, is poorly characterized in terms of cellular requirements and pathways. Conflicting reports attribute HPV-16 entry to clathrin-dependent and -independent mechanisms. To comprehensively describe the cell biological features of HPV-16 entry into human epithelial cells, we compared HPV-16 pseudovirion (PsV) infection in the context of cell perturbations (drug inhibition, siRNA silencing, overexpression of dominant mutants) to five other viruses (influenza A virus, Semliki Forest virus, simian virus 40, vesicular stomatitis virus, and vaccinia virus) with defined endocytic requirements. Our analysis included infection data, i.e. GFP expression after plasmid delivery by HPV-16 PsV, and endocytosis assays in combination with electron, immunofluorescence, and video microscopy. The results indicated that HPV-16 entry into HeLa and HaCaT cells was clathrin-, caveolin-, cholesterol- and dynamin-independent. The virus made use of a potentially novel ligand-induced endocytic pathway related to macropinocytosis. This pathway was distinct from classical macropinocytosis in regards to vesicle size, cholesterol-sensitivity, and GTPase requirements, but similar in respect to the need for tyrosine kinase signaling, actin dynamics, Na+/H+ exchangers, PAK-1 and PKC. After internalization the virus was transported to late endosomes and/or endolysosomes, and activated through exposure to low pH

The Circadian Light Table

Technological innovation provides us with lives that are happier, healthier, and longer than ever before in human history. Advancements in our lifetime have connected us in ways never before imaginable. Yet, despite its countless benefits, the progress of technology must be viewed critically at every forward step that is taken. We must be mindful of the changes we make to our lives, lest we create a digital world unsuited for our natural bodies and minds. As we spend more time indoors, under artificial lights, interacting with illuminated screens, we lose track of a vital connection with nature. Our circadian rhythm is a biological process that we share with nearly all living organisms. Informed by the rising and setting of the sun and other environmental factors, circadian rhythm regulates not only when we sleep, but our mental processes, emotional stability, and our chemical metabolisms. With increasingly sophisticated LED technology, we can design our environments to restore our natural cycle. With varying light intensity and color temperature, this illuminated table designed and built in Illinois's architecture graduate studio mimics natures rhythm and harmonizes with its users.Ope

Truss Chair

The Truss Chair is the culmination of a semester of research into furniture innovation through structural invention. As a multidisciplinary experiment, the Truss Chair research was conducted by graduate architecture student Aaron Laniosz in the industrial design studio of Professor David Weightman. The objective of the research was to explore the utilization of an architectural understanding of structure to the scale of a furniture object. In this application, the two-force member truss structural system creates opportunity for material efficiency and aesthetically stimulating geometry. The use of a space truss system breaks down the traditional understanding of a chairs components and reassembles a new organization of load bearing members. This image shows the final chair during the process of assembly, before the application of the chairs seat and back. This is the chairs structural skeleton.Ope

The Circadian Light Table

Technological innovation provides us with lives that are happier, healthier, and longer than ever before in human history. Advancements in our lifetime have connected us in ways never before imaginable. Yet, despite its countless benefits, the progress of technology must be viewed critically at every forward step that is taken. We must be mindful of the changes we make to our lives, lest we create a digital world unsuited for our natural bodies and minds. As we spend more time indoors, under artificial lights, interacting with illuminated screens, we lose track of a vital connection with nature. Our circadian rhythm is a biological process that we share with nearly all living organisms. Informed by the rising and setting of the sun and other environmental factors, circadian rhythm regulates not only when we sleep, but our mental processes, emotional stability, and our chemical metabolisms. With increasingly sophisticated LED technology, we can design our environments to restore our natural cycle. With varying light intensity and color temperature, this illuminated table designed and built in Illinois's architecture graduate studio mimics natures rhythm and harmonizes with its users.Ope

Allergic-dermatological symptoms and psychological variables in fibromyalgia: A preliminary study of their relationship

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Human Papillomavirus Type 16 Infection of Human Keratinocytes Requires Clathrin and Caveolin-1 and Is Brefeldin A Sensitive▿ †

Human papillomavirus type 16 (HPV16) has been identified as being the most common etiological agent leading to cervical cancer. Despite having a clear understanding of the role of HPV16 in oncogenesis, details of how HPV16 traffics during infection are poorly understood. HPV16 has been determined to enter via clathrin-mediated endocytosis, but the subsequent steps of HPV16 infection remain unclear. There is emerging evidence that several viruses take advantage of cross talk between routes of endocytosis. Specifically, JCV and bovine papillomavirus type 1 have been shown to enter cells by clathrin-dependent endocytosis and then require caveolin-1-mediated trafficking for infection. In this paper, we show that HPV16 is dependent on caveolin-1 after clathrin-mediated endocytosis. We provide evidence for the first time that HPV16 infection is dependent on trafficking to the endoplasmic reticulum (ER). This novel trafficking may explain the requirement for the caveolar pathway in HPV16 infection because clathrin-mediated endocytosis typically does not lead to the ER. Our data indicate that the infectious route for HPV16 following clathrin-mediated entry is caveolin-1 and COPI dependent. An understanding of the steps involved in HPV16 sorting and trafficking opens up the possibility of developing novel approaches to interfere with HPV16 infection and reduce the burden of papillomavirus diseases including cervical cancer