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The EVER proteins as a natural barrier against papillomaviruses: a new insight into the pathogenesis of human papillomavirus infections.

ABSTRACT: Infections by human papillomaviruses (HPVs) are the most frequently occurring sexually transmitted diseases. The crucial role of genital oncogenic HPV in cervical carcinoma development is now well established. In contrast, the role of cutaneous HPV in skin cancer development remains a matter of debate. Cutaneous beta-HPV strains show an amazing ubiquity. The fact that a few oncogenic genotypes cause cancers in patients suffering from epidermodysplasia verruciformis is in sharp contrast to the unapparent course of infection in the general population. Our recent investigations revealed that a natural barrier exists in humans, which protects them against infection with these papillomaviruses. A central role in the function of this HPV-specific barrier is played by a complex of the zinc-transporting proteins EVER1, EVER2, and ZnT-1, which maintain cellular zinc homeostasis. Apparently, the deregulation of the cellular zinc balance emerges as an important step in the life cycles not only of cutaneous but also of genital HPVs, although the latter viruses have developed a mechanism by which they can break the barrier and impose a zinc imbalance. Herein, we present a previously unpublished list of the cellular partners of EVER proteins, which points to future directions concerning investigations of the mechanisms of action of the EVER/ZnT-1 complex. We also present a general overview of the pathogenesis of HPV infections, taking into account the latest discoveries regarding the role of cellular zinc homeostasis in the HPV life cycle. We propose a potential model for the mechanism of function of the anti-HPV barrier.

SUBMITTER: Lazarczyk M

PROVIDER: S-EPMC2698414 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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The EVER proteins as a natural barrier against papillomaviruses: a new insight into the pathogenesis of human papillomavirus infections.

Lazarczyk Maciej M Cassonnet Patricia P Pons Christian C Jacob Yves Y Favre Michel M

Microbiology and molecular biology reviews : MMBR 20090601 2

Infections by human papillomaviruses (HPVs) are the most frequently occurring sexually transmitted diseases. The crucial role of genital oncogenic HPV in cervical carcinoma development is now well established. In contrast, the role of cutaneous HPV in skin cancer development remains a matter of debate. Cutaneous beta-HPV strains show an amazing ubiquity. The fact that a few oncogenic genotypes cause cancers in patients suffering from epidermodysplasia verruciformis is in sharp contrast to the un ...[more]

PMID: 19487731

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Project description:Viruses in the family Papillomaviridae have circular dsDNA genomes of approximately 5.7-8.6 kb that are packaged within non-enveloped, icosahedral capsids. The known papillomavirus (PV) representatives infect vertebrates, and there are currently more than 130 recognized PV species in more than 50 genera. We identified 12 novel avian papillomavirus (APV) types in wild birds that could represent five distinct species and two genera. Viruses were detected in paired oropharyngeal/cloacal swabs collected from six bird species, increasing the number of avian species known to harbor PVs by 40%. A new duck PV (DuPV-3) was found in mallard and American black duck (27.6% estimated prevalence) that was monophyletic with other known DuPVs. A single viral type was identified in Atlantic puffin (PuPV-1, 9.8% estimated prevalence), while a higher genetic diversity was found in other Charadriiformes. Specifically, three types [gull PV-1 (GuPV-1), -2, and -3] were identified in two gull species (estimated prevalence of 17% and 2.6% in American herring and great black-backed gull, respectively), and seven types [kittiwake PV-1 (KiPV-1) through -7] were found in black-legged kittiwake (81.3% estimated prevalence). Significantly higher DuPV-3 circulation was observed in spring compared to fall and in adults compared to juveniles. The studied host species' tendencies to be in crowded environments likely affect infection rates and their migratory behaviors could explain the high viral diversity, illustrating how host behavior can influence viral ecology and distribution. For DuPV-3, GuPV-1, PuPV-1, and KiPV-2, we obtained the complete genomic sequences, which showed the same organization as other known APVs. Phylogenetic analyses showed evidence for virus-host co-divergence at the host taxonomic levels of family, order, and inter-order, but we also observed that host-specificity constraints are relaxed among highly related hosts as we found cross-species transmission within ducks and within gulls. Furthermore, the phylogeny of viruses infecting the Charadriiformes did not match the host phylogeny and gull viruses formed distinct monophyletic clades with kittiwake viruses, possibly reflecting past host-switching events. Considering the vast PV genotype diversity in other hosts and the large number of bird species, many more APVs likely remain to be discovered.

Project description:BACKGROUND:Since late 2011, cases of suspected canine pseudorabies have increased in north China with the outbreak of swine pseudorabies in the same area, but the pathogenesis of canine Pseudorabies virus (PRV) infections in China is poorly understood. In this study, we investigated the pathogenesis of canine pseudorabies. METHODS:The pathological changes in 13 dogs that died of natural PRV infections (confirmed by pathogen detection) during 2011-2013 in Beijing were evaluated. An experimental study was also conducted in which healthy adult beagle dogs were administered PRV isolate BJ-YT by subcutaneous injection. The dog tissues were subjected to gross and microscopic examinations and immunohistochemical analysis and the dogs' serum cardiac troponin-I (cTn-I) was measured. RESULTS:Systemic hemorrhage and/or congestion were the most marked pathological changes in both the naturally and experimentally PRV-infected dogs. Macroscopically, the major lesions consisted of petechiae and ecchymoses in both the endocardium and epicardium, thrombi in the mitral valves, hemorrhage in the lungs and thymus, and incomplete contraction of the spleen. Microscopically, the major histopathological findings were systemic hemorrhage and congestion, nonsuppurative ganglioneuritis (in the experimentally infected dogs, unexamined in the naturally PRV-infected dogs), brainstem encephalitis (in the naturally infected dogs), necrosis or exudation in the myocardium, and lymphoid depletion in many lymphoid organs and tissues. Viral antigens were only detected in the brainstems and peripheral ganglia of the infected dogs. Serum cTn-I was significantly higher in the experimentally PRV-infected dogs with myocardial lesions than in the dogs without myocardial lesions. CONCLUSIONS:Based on these results, we conclude that virally induced systemic hemorrhage, peripheral nervous system pathology, and/or cardiac injury can individually or collectively cause death in PRV-infected dogs. The respiratory signs of the disease are attributed to cardiogenic lesions.

Dataset Information

The EVER proteins as a natural barrier against papillomaviruses: a new insight into the pathogenesis of human papillomavirus infections.

Publications

The EVER proteins as a natural barrier against papillomaviruses: a new insight into the pathogenesis of human papillomavirus infections.

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