HPV16 entry requires dynein for minus-end transport and utilizes kinesin Kif11 for plus-end transport along microtubules during mitosis.

Unlabelled: Human papillomaviruses (HPVs) travel from the trans-Golgi network (TGN) to the condensed (mitotic) chromosomes during mitosis. Partially uncoated HPV capsids utilize a unique vesicular structure for trafficking and nuclear import, which is directed by the minor capsid protein L2. However, it is still unknown which precise factors facilitate post-TGN HPV trafficking to the nucleus.

Emerging Fungal Pathogen Rhodotorula Species Isolated From a Patient With a Lung Malignancy.

is a genus of ubiquitous pigmented yeast found in the environment and as a commensal of human and animal microbiota. Previously considered nonpathogenic, has emerged as an important cause of nosocomial and opportunistic infections in susceptible patients. While spp.

Proteomic and mechanistic dissection of the poxvirus-customized ribosome.

Ribosomes are often viewed as protein synthesis machines that lack intrinsic regulatory capacity. However, studies have established that ribosomes can functionally diversify through changes in the composition of, or post-translational modifications to ribosomal subunit proteins (RPs). We recently found that poxviruses phosphorylate unique sites in the RP, receptor for activated C kinase 1 (RACK1) to enhance viral protein synthesis.

PML nuclear body-residing proteins sequentially associate with HPV genome after infectious nuclear delivery.

Subnuclear promyelocytic leukemia (PML) nuclear bodies (NBs) are targeted by many DNA viruses after nuclear delivery. PML protein is essential for formation of PML NBs. Sp100 and Small Ubiquitin-Like Modifier (SUMO) are also permanently residing within PML NBs.

Translational control during poxvirus infection.

Poxviruses are an unusual family of large double-stranded (ds) DNA viruses that exhibit an incredible degree of self-sufficiency and complexity in their replication and immune evasion strategies. Indeed, amongst their approximately 200 open reading frames (ORFs), poxviruses encode approximately 100 immunomodulatory proteins to counter host responses along with complete DNA synthesis, transcription, mRNA processing and cytoplasmic redox systems that enable them to replicate exclusively in the cytoplasm of infected cells. However, like all other viruses poxviruses do not encode ribosomes and therefore remain completely dependent on gaining access to the host translational machinery in order to synthesize viral proteins.

Poxviruses Evade Cytosolic Sensing through Disruption of an mTORC1-mTORC2 Regulatory Circuit.

Viruses employ elaborate strategies to coopt the cellular processes they require to replicate while simultaneously thwarting host antiviral responses. In many instances, how this is accomplished remains poorly understood. Here, we identify a protein, F17 encoded by cytoplasmically replicating poxviruses, that binds and sequesters Raptor and Rictor, regulators of mammalian target of rapamycin complexes mTORC1 and mTORC2, respectively.

ZNF598 Plays Distinct Roles in Interferon-Stimulated Gene Expression and Poxvirus Protein Synthesis.

Post-translational modification of ribosomal subunit proteins (RPs) is emerging as an important means of regulating gene expression. Recently, regulatory ubiquitination of small RPs RPS10 and RPS20 by the ubiquitin ligase ZNF598 was found to function in ribosome sensing and stalling on internally polyadenylated mRNAs during ribosome quality control (RQC). Here, we reveal that ZNF598 and RPS10 negatively regulate interferon-stimulated gene (ISG) expression in primary cells, depletion of which induced ISG expression and a broad antiviral state.

A new cell culture model to genetically dissect the complete human papillomavirus life cycle.

Herein, we describe a novel infection model that achieves highly efficient infection of primary keratinocytes with human papillomavirus type 16 (HPV16). This cell culture model does not depend on immortalization and is amenable to extensive genetic analyses. In monolayer cell culture, the early but not late promoter was active and yielded a spliced viral transcript pattern similar to HPV16-immortalized keratinocytes.

Human Papillomavirus Major Capsid Protein L1 Remains Associated with the Incoming Viral Genome throughout the Entry Process.

During infectious entry, acidification within the endosome triggers uncoating of the human papillomavirus (HPV) capsid, whereupon host cyclophilins facilitate the release of most of the major capsid protein, L1, from the minor capsid protein L2 and the viral genome. The L2/DNA complex traffics to the -Golgi network (TGN). After the onset of mitosis, HPV-harboring transport vesicles bud from the TGN, followed by association with mitotic chromosomes.

Cruising the cellular highways: How human papillomavirus travels from the surface to the nucleus.

The non-enveloped human papillomaviruses (HPVs) specifically target epithelial cells of the skin and mucosa. Successful infection requires a lesion in the stratified tissue for access to the basal cells. Herein, we discuss our recent progress in understanding binding, internalization, uncoating, and intracellular trafficking of HPV particles.

Incoming human papillomavirus 16 genome is lost in PML protein-deficient HaCaT keratinocytes.

Unlabelled: Human papillomaviruses (HPVs) target promyelocytic leukemia (PML) nuclear bodies (NBs) during infectious entry and PML protein is important for efficient transcription of incoming viral genome. However, the transcriptional down regulation was shown to be promoter-independent in that heterologous promoters delivered by papillomavirus particles were also affected. To further investigate the role of PML protein in HPV entry, we used small hairpin RNA to knockdown PML protein in HaCaT keratinocytes.

Human Papillomavirus Entry: Hiding in a Bubble.

Incoming human papillomavirus (HPV) utilize vesicular transport to traffic from the plasma membrane to the trans-Golgi network. Following nuclear envelope breakdown during mitosis, the viral DNA associates with condensed chromosomes utilizing spindle microtubules for delivery. Most intriguingly, the viral DNA resides in a transport vesicle until mitosis is completed and the nuclear envelope has reformed.

Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry.

Unlabelled: The human papillomavirus (HPV) capsid is composed of the major capsid protein L1 and the minor capsid protein L2. During entry, the HPV capsid undergoes numerous conformational changes that result in endosomal uptake and subsequent trafficking of the L2 protein in complex with the viral DNA to the trans-Golgi network. To facilitate this transport, the L2 protein harbors a number of putative motifs that, if capable of direct interaction, would interact with cytosolic host cell factors.

The nuclear retention signal of HPV16 L2 protein is essential for incoming viral genome to transverse the trans-Golgi network.

The Human papillomavirus (HPV) capsid is composed of the major and minor capsid proteins, L1 and L2, respectively. Infectious entry requires a complex series of conformational changes in both proteins that lead to uptake and allow uncoating to occur. During entry, the capsid is disassembled and host cyclophilins dissociate L1 protein from the L2/DNA complex.