bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of a Zebrafish Infection Model for the Study of Wild-Type and Recombinant European Sheatfish Virus
Authors: Martín Verónica , Mavian Carla , López Bueno Alberto , de Molina Antonio , Díaz Eduardo , Andrés Germán , Alcami Antonio , Alejo Alí 
Published: August 2015

ABSTRACT
Amphibian-like ranaviruses include pathogens of fish, amphibians, and reptiles that have recently evolved from a fish-infecting ancestor. The molecular determinants of host range and virulence in this group are largely unknown, and currently fish infection models are lacking. We show that European sheatfish virus (ESV) can productively infect zebrafish, causing a lethal pathology, and describe a method for the generation of recombinant ESV, establishing a useful model for the study of fish ranavirus infections.
Host Determinants of Prion Strain Diversity Independent of Prion Protein Genotype
Authors: Crowell Jenna , Hughson Andrew , Caughey Byron , Bessen Richard A. 
Published: August 2015

ABSTRACT

Phenotypic diversity in prion diseases can be specified by prion strains in which biological traits are propagated through an epigenetic mechanism mediated by distinct PrP
Sc
conformations. We investigated the role of host-dependent factors on phenotypic diversity of chronic wasting disease (CWD) in different host species that express the same prion protein gene (
Prnp
). Two CWD strains that have distinct biological, biochemical, and pathological features were identified in transgenic mice that express the Syrian golden hamster (SGH)
Prnp
. The CKY strain of CWD had a shorter incubation period than the WST strain of CWD, but after transmission to SGH, the incubation period of CKY CWD was ∼150 days longer than WST CWD. Limited proteinase K digestion revealed strain-specific PrP
Sc
polypeptide patterns that were maintained in both hosts, but the solubility and conformational stability of PrP
Sc
differed for the CWD strains in a host-dependent manner. WST CWD produced PrP
Sc
amyloid plaques in the brain of the SGH that were partially insoluble and stable at a high concentration of protein denaturant. However, in transgenic mice, PrP
Sc
from WST CWD did not assemble into plaques, was highly soluble, and had low conformational stability. Similar studies using the HY and DY strains of transmissible mink encephalopathy resulted in minor differences in prion biological and PrP
Sc
properties between transgenic mice and SGH. These findings indicate that host-specific pathways that are independent of
Prnp
can alter the PrP
Sc
conformation of certain prion strains, leading to changes in the biophysical properties of PrP
Sc
, neuropathology, and clinical prion disease.

IMPORTANCE
Prions are misfolded pathogenic proteins that cause neurodegeneration in humans and animals. Transmissible prion diseases exhibit a spectrum of disease phenotypes and the basis of this diversity is encoded in the structure of the pathogenic prion protein and propagated by an epigenetic mechanism. In the present study, we investigated prion diversity in two hosts species that express the same prion protein gene. While prior reports have demonstrated that prion strain properties are stable upon infection of the same host species and prion protein genotype, our findings indicate that certain prion strains can undergo dramatic changes in biological properties that are not dependent on the prion protein. Therefore, host factors independent of the prion protein can affect prion diversity. Understanding how host pathways can modify prion disease phenotypes may provide clues on how to alter prion formation and lead to treatments for prion, and other, human neurodegenerative diseases of protein misfolding.
Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein
Authors: Dick Robert A. , Datta Siddhartha A. K. , Nanda Hirsh , Fang Xianyang , Wen Yi , Barros Marilia , Wang Yun-Xing , Rein Alan , Vogt Volker M. 
Published: August 2015

ABSTRACT

Previously, no retroviral Gag protein has been highly purified in milligram quantities and in a biologically relevant and active form. We have purified Rous sarcoma virus (RSV) Gag protein and in parallel several truncation mutants of Gag and have studied their biophysical properties and membrane interactions
in vitro
. RSV Gag is unusual in that it is not naturally myristoylated. From its ability to assemble into virus-like particles
in vitro
, we infer that RSV Gag is biologically active. By size exclusion chromatography and small-angle X-ray scattering, Gag in solution appears extended and flexible, in contrast to previous reports on unmyristoylated HIV-1 Gag, which is compact. However, by neutron reflectometry measurements of RSV Gag bound to a supported bilayer, the protein appears to adopt a more compact, folded-over conformation. At physiological ionic strength, purified Gag binds strongly to liposomes containing acidic lipids. This interaction is stimulated by physiological levels of phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and by cholesterol. However, unlike HIV-1 Gag, RSV Gag shows no sensitivity to acyl chain saturation. In contrast with full-length RSV Gag, the purified MA domain of Gag binds to liposomes only weakly. Similarly, both an N-terminally truncated version of Gag that is missing the MA domain and a C-terminally truncated version that is missing the NC domain bind only weakly. These results imply that NC contributes to membrane interaction
in vitro
, either by directly contacting acidic lipids or by promoting Gag multimerization.

IMPORTANCE
Retroviruses like HIV assemble at and bud from the plasma membrane of cells. Assembly requires the interaction between thousands of Gag molecules to form a lattice. Previous work indicated that lattice formation at the plasma membrane is influenced by the conformation of monomeric HIV. We have extended this work to the more tractable RSV Gag. Our results show that RSV Gag is highly flexible and can adopt a folded-over conformation on a lipid bilayer, implicating both the N and C termini in membrane binding. In addition, binding of Gag to membranes is diminished when either terminal domain is truncated. RSV Gag membrane association is significantly less sensitive than HIV Gag membrane association to lipid acyl chain saturation. These findings shed light on Gag assembly and membrane binding, critical steps in the viral life cycle and an untapped target for antiretroviral drugs.
Role for a Zinc Finger Protein (Zfp111) in Transformation of 208F Rat Fibroblasts by Jaagsiekte Sheep Retrovirus Envelope Protein
Authors: Hsu Tom , Phung An , Choe Kevin , Kim Jung Woo , Fan Hung 
Published: August 2015

ABSTRACT

The native envelope gene (
env
) of Jaagsiekte sheep retrovirus (JSRV) also acts as an oncogene. To investigate the mechanism of transformation, we performed yeast 2-hybrid screening for cellular proteins that interact with Env. Among several candidates, we identified mouse or rat zinc finger protein 111 (
zfp111
). The interaction between Env and Zfp111 was confirmed through
in vivo
coimmunoprecipitation assays. Knockdown of endogenous Zfp111 caused a decrease in cell transformation by JSRV Env, while overexpression of Zfp111 increased overall Env transformation, supporting a role for Zfp111 in Env transformation. Knockdown of Zfp111 had no effect on the growth rate of parental rat 208F cells, while it decreased the proliferation rate of JSRV-transformed 208F cells, suggesting that JSRV-transformed cells became dependent on Zfp111. In addition, Zfp111 preferentially bound to a higher-mobility form of JSRV Env that has not been described previously. The higher-mobility form of Env (P70

env

) was found exclusively in the nuclear fraction, and size of its polypeptide backbone was the same as that of the cytoplasmic Env polyprotein (Pr80

env

). The differences in glycosylation between the two versions of Env were characterized. These results identify a novel cellular protein, Zfp111, that binds to the JSRV Env protein, and this binding plays a role in Env transformation. These results indicate that JSRV transformation also involves proteins and interactions in the nucleus.

IMPORTANCE
The envelope protein (Env) of Jaagsiekte sheep retrovirus (JSRV) is an oncogene, but its mechanism of cell transformation is still unclear. Here we identified seven candidate cellular proteins that can interact with JSRV Env by yeast two-hybrid screening. This study focused on one of the seven candidates, zinc finger protein 111 (Zfp111). Zfp111 was shown to interact with JSRV Env in cells and to be involved in JSRV transformation. Moreover, coexpression of JSRV Env and Zfp111 led to the identification of a novel nuclear form of the JSRV Env protein that binds Zfp111. Nuclear Env was found to differ by glycosylation from the cytoplasmic Env precursor to the virion envelope proteins. These results suggest that JSRV Env transformation may involve nuclear events such as an alteration in transcription mediated by Env-Zfp111 interactions.
Soluble Envelope Glycoprotein Trimers from a CD4-Independent HIV-1 Elicit Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies in Guinea Pigs
Authors: Murray Marta K. , Teran Victor A. , Chapleau Jean-Philippe , Wang Baomin , Kim Su Hyon , LaBranche Celia C. , Richard Jonathan , Montefiori David C. , Finzi Andrés , Yuan Wen 
Published: August 2015

ABSTRACT
CD4-independent HIV-1 variants can infect coreceptor-expressing cells lacking CD4. The envelope (Env) glycoproteins on these HIV-1 variants expose a coreceptor binding site that overlaps some CD4-induced (CD4i) epitopes. Reports have demonstrated that CD4i antibodies mediate antibody-dependent cellular cytotoxicity (ADCC). Here we investigated the immunogenicity of soluble Env trimers (sgp140) from a CD4-independent HIV-1 in guinea pigs and found that the sgp140 elicited ADCC-mediating antibodies. Therefore, these sgp140 might be useful in vaccine regimens aimed at eliciting ADCC responses.
Structural and Functional Diversity of Nairovirus-Encoded Nucleoproteins
Authors: Wang Wenming , Liu Xiang , Wang Xu , Dong Hui , Ma Chao , Wang Jingmin , Liu Baocheng , Mao Yonghong , Wang Ying , Li Ting , Yang Cheng , Guo Yu 
Published: August 2015

ABSTRACT
The nairoviruses include assorted tick-borne bunyaviruses that are emerging as causative agents of infectious diseases among humans and animals. As negative-sense single-stranded RNA (−ssRNA) viruses, nairoviruses encode nucleoprotein (NP) that encapsidates the genomic RNA and further forms ribonucleoprotein (RNP) complex with viral RNA-dependent RNA polymerase (RdRp). We previously revealed that the monomeric NP encoded by Crimean-Congo hemorrhagic fever virus (CCHFV) presents a racket-shaped structure and shows unusual DNA-specific endonuclease activity. To examine the structural and biological variation of nairovirus-encoded NPs, here, we systematically solved the crystal structures of NPs encoded by various nairoviruses, including Hazara virus (HAZV), Kupe virus (KUPV), and Erve virus (ERVEV). Combined with biochemical analysis, our results generate a clearer picture to aid in the understanding of the functional diversity of nairovirus-encoded NPs and the formation of nairovirus RNPs.

IMPORTANCE
Nairoviruses comprise several tick-borne bunyaviruses that are emerging as causative agents of infectious diseases among humans and animals; however, little is known of the nairovirus genome assembly and transcription mechanisms. Based on the previous study of CCHFV NP reported by different research groups, we systematically investigate here the structural and functional diversity among three different nairoviruses. This work provides important information on nairovirus nucleoprotein function and the formation of RNPs.
Suppressor of Cytokine Signaling 3 Is an Inducible Host Factor That Regulates Virus Egress during Ebola Virus Infection
Authors: Okumura Atsushi , Rasmussen Angela L. , Halfmann Peter , Feldmann Friederike , Yoshimura Akihiko , Feldmann Heinz , Kawaoka Yoshihiro , Harty Ronald N. , Katze Michael G. 
Published: August 2015

ABSTRACTEbola virus (EBOV) initially targets monocytes and macrophages, which can lead to the release of proinflammatory cytokines and chemokines. These inflammatory cytokines are thought to contribute to the development of circulatory shock seen in fatal EBOV infections. The VP40 matrix protein is a key viral structural protein that is critical for virion egress. Physical and functional interactions between VP40 and host proteins such as Tsg101 and Nedd4 facilitate efficient release of VP40-driven virus-like particles (VLPs) and infectious virus. Here, we show that host suppressor of cytokine signaling 3 (SOCS3) can also bind to EBOV VP40, leading to enhanced ubiquitinylation and egress of VP40. Indeed, titers of infectious EBOV derived from SOCS3 knockout mouse embryonic fibroblasts (MEFs) were significantly reduced compared to those from wild-type (WT) MEFs at 24 and 48 h postinfection. Importantly, this reduced virus yield could be rescued back to WT levels by exogenously expressing SOCS3. Lastly, we show that SOCS3 expression is induced by EBOV glycoprotein (GP) expression and that VLPs containing EBOV VP40 and GP induced production of proinflammatory cytokines, which induced SOCS3 for negative-feedback regulation. These data indicate that host innate immune protein SOCS3 may play an important role in budding and pathogenesis of EBOV.IMPORTANCEThe VP40 matrix protein is a key structural protein critical for Ebola virus budding. Physical and functional interactions between VP40 and host proteins such as Tsg101 and Nedd4 facilitate efficient release of VLPs and infectious virus. We reported that host TLR4 is a sensor for Ebola GP on VLPs and that the resultant TLR4 signaling pathways lead to the production of proinflammatory cytokines. Host SOCS3 regulates the innate immune response by controlling and limiting the proinflammatory response through negative-feedback inhibition of cytokine receptors. We present evidence that Ebola virus VLPs stimulate induction of SOCS3 as well as proinflammatory cytokines, and that expression of human SOCS3 enhances budding of Ebola VLPs and infectious virus via a mechanism linked to the host ubiquitinylation machinery.
Infections on Cruise Ships
Authors: Kak Vivek 
Published: August 2015

ABSTRACT
The modern cruise ship is a small city on the seas, with populations as large as 5,000 seen on large ships. The growth of the cruise ship industry has continued in the twenty-first century, and it was estimated that nearly 21.3 million passengers traveled on cruise ships in 2013, with the majority of these sailing from North America. The presence of large numbers of individuals in close proximity to each other facilitates transmission of infectious diseases, often through person-to-person spread or via contaminated food or water. An infectious agent introduced into the environment of a cruise ship has the potential to be distributed widely across the ship and to cause significant morbidity. The median cruise ship passenger is over 45 years old and often has chronic medical problems, so it is important that, to have a safe cruise ship experience, any potential for the introduction of an infecting agent as well as its transmission be minimized. The majority of cruise ship infections involve respiratory and gastrointestinal infections. This article discusses infectious outbreaks on cruise ships and suggests preventative measures for passengers who plan to travel on cruise ships.
The Role of Vibrios in Diseases of Corals
Authors: Munn Colin B. 
Published: August 2015

ABSTRACT

The tissue, skeleton, and secreted mucus of corals supports a highly dynamic and diverse community of microbes, which play a major role in the health status of corals such as the provision of essential nutrients or the metabolism of waste products. However, members of the
Vibrio
genus are prominent as causative agents of disease in corals. The aim of this chapter is to review our understanding of the spectrum of disease effects displayed by coral-associated vibrios, with a particular emphasis on the few species where detailed studies of pathogenicity have been conducted. The role of
Vibrio shilonii
in seasonal bleaching of
Oculina patagonica
and the development of the coral probiotic hypothesis is reviewed, pointing to unanswered questions about this phenomenon. Detailed consideration is given to studies of
V. coralliilyticus
and related pathogens and changes in the dominance of vibrios associated with coral bleaching. Other
Vibrio
-associated disease syndromes discussed include yellow band/blotch disease and tissue necrosis in temperate gorgonian corals. The review includes analysis of the role of enzymes, resistance to oxidative stress, and quorum sensing in virulence of coral-associated vibrios. The review concludes that we should probably regard most—possibly all—vibrios as “opportunistic” pathogens which, under certain environmental conditions, are capable of overwhelming the defense mechanisms of appropriate hosts, leading to rapid growth and tissue destruction.
Relationship between education levels and booster counselling sessions on smoking cessation among Chinese smokers
Authors: Wu Lei , He Yao , Jiang Bin , Zuo Fang , Liu Qinghui , Zhang Li , Zhou Changxi , Liu Miao , Chen Hongyan 
Published: August 2015

ObjectivesAlthough various effective interventions are available to help individuals quit smoking, the effect of educational levels on cessation rates has rarely been studied, and of the few intervention studies on this topic, the results have been conflicting.Design and settingFrom October 2008 to August 2013, a partly retrospective non-randomised study was conducted in a smoking cessation clinic of a large general hospital in Beijing, China.ParticipantsIn total, 547 Chinese smokers who sought treatment were divided into two groups: a face-to-face counselling group (FC, n=149) and an FC group subjected to four telephone follow-up sessions (FCF, n=398).OutcomesWe evaluated self-reported cessation rates by day 7 and after 6 and 12 months and stratified the two groups by education levels.ResultsThe 7-day and 6-month and 12-month continuous cessation rates of smokers of low education levels in the FC group at the time of the 12-month follow-up were 12.5%, 7.1% and 7.1%, respectively, which were lower than those of the highly educated smokers (16.1%, 12.9% and 9.7%, respectively). The results were opposite for the FCF group. The corresponding results for the highly educated smokers of the FCF group were 25.0%, 17.2% and 10.3%, respectively, which were lower than those for the smokers of low education levels (28.3%, 22.9% and 18.1%, respectively). However, significant differences were observed only among the FCF group participants who had experienced 12 months of continuous abstinence, and the crude OR for these individuals was recorded at 0.52 (0.29 to 0.93), p=0.03. A stepwise logistic regression showed that education levels may play a role in various intervention methods. Being married and higher Fagerström test scores were also predictors of cessation tendencies.ConclusionsEducation levels may affect the benefits of booster counselling sessions on smoking cessation among Chinese smokers.
Retrospective study of the predictors of mortality and radiographic deterioration in 782 patients with nodular/bronchiectaticMycobacterium aviumcomplex lung disease
Authors: Gochi Mina , Takayanagi Noboru , Kanauchi Tetsu , Ishiguro Takashi , Yanagisawa Tsutomu , Sugita Yutaka 
Published: August 2015

ObjectivesSome patients with nodular/bronchiectaticMycobacterium aviumcomplex lung disease (NB MAC-LD) deteriorate and die. The main aim of the study is to evaluate the prognostic factors and radiographic outcomes in patients with NB MAC-LD.SettingRetrospective single-centre review.Participants782 HIV-negative patients with NB MAC-LD treated at our institution in Japan.Primary and secondary outcome measuresAll-cause and MAC-LD progression mortality rates and the prognostic factors, and radiographic deterioration rates and the prognostic factors.ResultsMean age was 68.1 years, and median follow-up period was 4.3 years. Death from any cause and progression of MAC lung disease (MAC-LD) occurred in 130 (16.6%), and 19 (2.4%) patients, respectively. All-cause and MAC-LD progression 10-year mortality rates were 27.4% and 4.8%, respectively. In 536 patients with MAC-LD who were followed-up for more than 1 year, radiographic deterioration occurred in 221 (41.2%) patients and median time-to-radiographic deterioration was 9 years. A multivariate Cox proportional hazard model showed male sex, older age, body mass index <18.5 kg/m2, absence of bloody sputum, hypoalbuminaemia and erythrocyte sedimentation rate >40 mm/h to be negative prognostic factors for all-cause mortality, and the presence of idiopathic pulmonary fibrosis, haemoglobin <11.3 mg/dL, C reactive protein >1.0 mg/dL and the presence of cavity to be negative prognostic factors for radiographic deterioration.ConclusionsOnly 2.4% of patients with NB MAC-LD died from MAC-LD progression. As clinical trials testing the effectiveness of drug therapy in patients with NB MAC-LD are being designed and implemented, the primary end point could be time-to-radiographic deterioration, and trial patients need to be stratified according to these prognostic factors before randomisation.
Plasma levels of matrix metalloproteinase-2 and -9 in male and female patients with cirrhosis of different aetiologies
Authors: Huang Chih-Yang , Tseng Kuo-Chih , Lin Ming-Nan , Tsai Jen-Pi , Su Cheng-Chuan 
Published: August 2015

BackgroundLiver fibrosis and cirrhosis may be reversible in some circumstances. Reliable diagnostic tests are necessary for monitoring hepatic fibrogenesis. Matrix metalloproteinase (MMP)-2 and MMP-9 are two of the major MMPs in the circulation and may be most relevant to hepatic fibrosis. The behaviour of MMPs may be significantly different in men and women and may also differ in cases of cirrhosis of various aetiologies.AimsTo evaluate the manifestations of MMP-2 and MMP-9 in liver cirrhosis of different aetiologies in men and women and to compare these patterns with those of healthy controls.MethodsWe measured MMP-2 and MMP-9 levels in plasma samples from 112 patients with cirrhosis and 112 age- and gender-matched healthy controls. We then correlated these MMP levels with gender and disease aetiology.ResultsPlasma MMP-2 concentrations in patients showed a trend towards increasing values with cirrhosis severity and were markedly increased in patients regardless of gender and aetiology compared with healthy controls (p<0.0001). Plasma mean MMP-9 levels were comparable in patients with cirrhosis and controls, but increased with disease severity. They were significantly lower in patients (130.5 ng/mL), female patients (85.4 ng/mL) and male patients (150.4 ng/mL) with mild cirrhosis than in controls (163.2 ng/mL), female controls (162.5 ng/mL) and male controls (163.3 ng/mL) (p=0.001, 0.041 and 0.009, respectively). MMP-2 and MMP-9 concentrations were not significantly different between genders among controls and among various patient subgroups.ConclusionsPlasma MMP-2 level may be a useful diagnostic marker for monitoring hepatic fibrogenesis in patients with disease of different aetiologies.