bluuebunny/crossref_metadata_2025_split huggingface dataset:
The NS1 Protein of Influenza A Virus Interacts with Cellular Processing Bodies and Stress Granules through RNA-Associated Protein 55 (RAP55) during Virus Infection
Authors: Mok Bobo Wing-Yee , Song Wenjun , Wang Pui , Tai Hung , Chen Yixin , Zheng Min , Wen Xi , Lau Siu-Ying , Wu Wai Lan , Matsumoto Ken , Yuen Kwok-Yung , Chen Honglin 
Published: September 2012

ABSTRACT
The nonstructural protein (NS1) of influenza A virus performs multiple functions in the virus life cycle. Proteomic screening for cellular proteins which interact with NS1 identified the cellular protein RAP55, which is one of the components of cellular processing bodies (P-bodies) and stress granules. To verify whether NS1 interacts with cellular P-bodies, interactions between NS1, RAP55, and other P-body-associated proteins (Ago1, Ago2, and DCP1a) were confirmed using coimmunoprecipitation and cellular colocalization assays. Overexpression of RAP55 induced RAP55-associated stress granule formation and suppressed virus replication. Knockdown of RAP55 with small interfering RNA (siRNA) or expression of a dominant-negative mutant RAP55 protein with defective interaction with P-bodies blocked NS1 colocalization to P-bodies in cells. Expression of NS1 inhibited RAP55 expression and formation of RAP55-associated P-bodies/stress granules. The viral nucleoprotein (NP) was found to be targeted to stress granules in the absence of NS1 but localized to P-bodies when NS1 was coexpressed. Restriction of virus replication via P-bodies occurred in the early phases of infection, as the number of RAP55-associated P-bodies in cells diminished over the course of virus infection. NS1 interaction with RAP55-associated P-bodies/stress granules was associated with RNA binding and mediated via a protein kinase R (PKR)-interacting viral element. Mutations introduced into either RNA binding sites (R38 and K41) or PKR interaction sites (I123, M124, K126, and N127) caused NS1 proteins to lose the ability to interact with RAP55 and to inhibit stress granules. These results reveal an interplay between virus and host during virus replication in which NP is targeted to P-bodies/stress granules while NS1 counteracts this host restriction mechanism.
Incorporation of Host Complement Regulatory Proteins into Newcastle Disease Virus Enhances Complement Evasion
Authors: Biswas Moanaro , Johnson John B. , Kumar Sandeep R. P. , Parks Griffith D. , Subbiah Elankumaran 
Published: September 2012

ABSTRACTNewcastle disease virus (NDV), an avian paramyxovirus, is inherently tumor selective and is currently being considered as a clinical oncolytic virus and vaccine vector. In this study, we analyzed the effect of complement on the neutralization of NDV purified from embryonated chicken eggs, a common source for virus production. Fresh normal human serum (NHS) neutralized NDV by multiple pathways of complement activation, independent of neutralizing antibodies. Neutralization was associated with C3 deposition and the activation of C2, C3, C4, and C5 components. Interestingly, NDV grown in mammalian cell lines was resistant to complement neutralization by NHS. To confirm whether the incorporation of regulators of complement activity (RCA) into the viral envelope afforded complement resistance, we grew NDV in CHO cells stably transfected with CD46 or HeLa cells, which strongly express CD46 and CD55. NDV grown in RCA-expressing cells was resistant to complement by incorporating CD46 and CD55 on virions. Mammalian CD46 and CD55 molecules on virions exhibited homologous restriction, since chicken sera devoid of neutralizing antibodies to NDV were able to effectively neutralize these virions. The incorporation of chicken RCA into NDV produced in embryonated eggs similarly provided species specificity toward chicken sera.
Differential Clade-Specific HLA-B*3501 Association with HIV-1 Disease Outcome Is Linked to Immunogenicity of a Single Gag Epitope
Authors: Matthews Philippa C. , Koyanagi Madoka , Kløverpris Henrik N. , Harndahl Mikkel , Stryhn Anette , Akahoshi Tomohiro , Gatanaga Hiroyuki , Oka Shinichi , Juarez Molina Claudia , Valenzuela Ponce Humberto , Avila Rios Santiago , Cole David , Carlson Jonathan , Payne Rebecca P. , Ogwu Anthony , Bere Alfred , Ndung'u Thumbi , Gounder Kamini , Chen Fabian , Riddell Lynn , Luzzi Graz , Shapiro Roger , Brander Christian , Walker Bruce , Sewell Andrew K. , Reyes Teran Gustavo , Heckerman David , Hunter Eric , Buus Søren , Takiguchi Masafumi , Goulder Philip J. R. 
Published: September 2012

ABSTRACTThe strongest genetic influence on immune control in HIV-1 infection is the HLA class I genotype. Rapid disease progression in B-clade infection has been linked to HLA-B*35 expression, in particular to the less common HLA-B*3502 and HLA-B*3503 subtypes but also to the most prevalent subtype, HLA-B*3501. In these studies we first demonstrated that whereas HLA-B*3501 is associated with a high viral set point in two further B-clade-infected cohorts, in Japan and Mexico, this association does not hold in two large C-clade-infected African cohorts. We tested the hypothesis that clade-specific differences in HLA associations with disease outcomes may be related to distinct targeting of critical CD8+T-cell epitopes. We observed that only one epitope was significantly targeted differentially, namely, the Gag-specific epitope NPPIPVGDIY (NY10, Gag positions 253 to 262) (P= 2 × 10−5). In common with two other HLA-B*3501-restricted epitopes, in Gag and Nef, that were not targeted differentially, a response toward NY10 was associated with a significantly lower viral set point. Nonimmunogenicity of NY10 in B-clade-infected subjects derives from the Gag-D260E polymorphism present in ∼90% of B-clade sequences, which critically reduces recognition of the Gag NY10 epitope. These data suggest that in spite of any inherent HLA-linked T-cell receptor repertoire differences that may exist, maximizing the breadth of the Gag-specific CD8+T-cell response, by the addition of even a single epitope, may be of overriding importance in achieving immune control of HIV infection. This distinction is of direct relevance to development of vaccines designed to optimize the anti-HIV CD8+T-cell response in all individuals, irrespective of HLA type.
MicroRNAs and Unusual Small RNAs Discovered in Kaposi's Sarcoma-Associated Herpesvirus Virions
Authors: Lin Xianzhi , Li Xiaofan , Liang Deguang , Lan Ke 
Published: September 2012

ABSTRACT

It is widely held that any given virus uses only one type of nucleic acid for genetic information storage. However, this consensus has been challenged slightly by several recent studies showing that many RNA species are present within a range of DNA viruses that include Kaposi's sarcoma-associated herpesvirus (KSHV). RNAs extracted from purified DNA virus particles exhibit great diversity in terms of length, abundance, temporal expression, cellular localization, and coding capacity during viral infection. In addition to known RNA species, the current study showed that small regulatory RNAs were present in KSHV virions. A large number of viral and cellular microRNAs (miRNAs), as well as unusual small RNAs (usRNAs), were detected in KSHV virions by using deep sequencing. Both viral and host miRNAs detected in small RNAs extracted from KSHV virions were further shown to colocalize with KSHV virions directly by
in situ
hybridization (ISH)-electron microscopy (EM) (ISH-EM). Some of these miRNAs were differentially present in the host cells and KSHV virions, suggesting that they are not randomly present in KSHV virions. The virional miRNAs could be transported into host cells, and they are biologically functional during
de novo
viral infection. Our study revealed miRNAs and usRNAs as a novel group of components in KSHV virions.
Essential Cell-Autonomous Role for Interferon (IFN) Regulatory Factor 1 in IFN-γ-Mediated Inhibition of Norovirus Replication in Macrophages
Authors: Maloney Nicole S. , Thackray Larissa B. , Goel Gautam , Hwang Seungmin , Duan Erning , Vachharajani Punit , Xavier Ramnik , Virgin Herbert W. 
Published: September 2012

ABSTRACT

Noroviruses (NVs) cause the majority of cases of epidemic nonbacterial gastroenteritis worldwide and contribute to endemic enteric disease. However, the molecular mechanisms responsible for immune control of their replication are not completely understood. Here we report that the transcription factor interferon regulatory factor 1 (IRF-1) is required for control of murine NV (MNV) replication and pathogenesis
in vivo
. This led us to studies documenting a cell-autonomous role for IRF-1 in gamma interferon (IFN-γ)-mediated inhibition of MNV replication in primary macrophages. This role of IRF-1 in the inhibition of MNV replication by IFN-γ is independent of IFN-αβ signaling. While the signal transducer and activator of transcription STAT-1 was also required for IFN-γ-mediated inhibition of MNV replication
in vitro
, class II transactivator (CIITA), interferon regulatory factor 3 (IRF-3), and interferon regulatory factor 7 (IRF-7) were not required. We therefore hypothesized that there must be a subset of IFN-stimulated genes (ISGs) regulated by IFN-γ in a manner dependent only on STAT-1 and IRF-1. Analysis of transcriptional profiles of macrophages lacking various transcription factors confirmed this hypothesis. These studies identify a key role for IRF-1 in IFN-γ-dependent control of norovirus infection in mice and macrophages.
Long-Term Nonprogressor and Elite Controller Patients Who Control Viremia Have a Higher Percentage of Methylation in Their HIV-1 Proviral Promoters than Aviremic Patients Receiving Highly Active Antiretroviral Therapy
Authors: Palacios Juan Antonio , Pérez-Piñar Teresa , Toro Carlos , Sanz-Minguela Beatriz , Moreno Victoria , Valencia Eulalia , Gómez-Hernando César , Rodés Berta 
Published: September 2012

ABSTRACT
Several factors are involved in the control of HIV transcription/replication, including epigenetic modifications at the promoter level. Analysis of the HIV long terminal repeat (LTR) methylation status in infected patients controlling viremia is scarce. Herein, we show a higher degree of DNA methylation in the 5′-LTR of long-term nonprogressor and elite controller (LTNP/EC) versus progressor patients and a positive correlation with time of infection, indicating a certain contribution of HIV LTR silencing in reducing the number of replicating viruses which may account for a delayed progression.
Double-Stranded RNA Induces Biphasic STAT1 Phosphorylation by both Type I Interferon (IFN)-Dependent and Type I IFN-Independent Pathways
Authors: Dempoya Junichi , Matsumiya Tomoh , Imaizumi Tadaatsu , Hayakari Ryo , Xing Fei , Yoshida Hidemi , Okumura Ken , Satoh Kei 
Published: September 2012

ABSTRACT
Upon viral infection, pattern recognition receptors sense viral nucleic acids, leading to the production of type I interferons (IFNs), which initiate antiviral activities. Type I IFNs bind to their cognate receptor, IFNAR, resulting in the activation of signal-transducing activators of transcription 1 (STAT1). Thus, it has long been thought that double-stranded RNA (dsRNA)-induced STAT1 phosphorylation is mediated by the transactivation of type I IFN signaling. Foreign RNA, such as viral RNA, in cells is sensed by the cytoplasmic sensors retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA-5). In this study, we explored the molecular mechanism responsible for STAT1 phosphorylation in response to the sensing of dsRNA by cytosolic RNA sensors. Polyinosinic-poly(C) [poly(I:C)], a synthetic dsRNA that is sensed by both RIG-I and MDA-5, induces STAT1 phosphorylation. We found that the poly(I:C)-induced initial phosphorylation of STAT1 is dependent on the RIG-I pathway and that MDA-5 is not involved in STAT1 phosphorylation. Furthermore, pretreatment of the cells with neutralizing antibody targeting the IFN receptor suppressed the initial STAT1 phosphorylation in response to poly(I:C), suggesting that this initial phosphorylation event is predominantly type I IFN dependent. In contrast, neither the known RIG-I pathway nor type I IFN is involved in the late phosphorylation of STAT1. In addition, poly(I:C) stimulated STAT1 phosphorylation in type I IFN receptor-deficient U5A cells with delayed kinetics. Collectively, our study provides evidence of a comprehensive regulatory mechanism in which dsRNA induces STAT1 phosphorylation, indicating the importance of STAT1 in maintaining very tight regulation of the innate immune system.
Structure of Hepatitis C Virus Envelope Glycoprotein E2 Antigenic Site 412 to 423 in Complex with Antibody AP33
Authors: Kong Leopold , Giang Erick , Nieusma Travis , Robbins Justin B. , Deller Marc C. , Stanfield Robyn L. , Wilson Ian A. , Law Mansun 
Published: September 2012

ABSTRACT
We have determined the crystal structure of the broadly neutralizing antibody (bnAb) AP33, bound to a peptide corresponding to hepatitis C virus (HCV) E2 envelope glycoprotein antigenic site 412 to 423. Comparison with bnAb HCV1 bound to the same epitope reveals a different angle of approach to the antigen by bnAb AP33 and slight variation in its β-hairpin conformation of the epitope. These structures establish two different modes of binding to E2 that antibodies adopt to neutralize diverse HCV.
A Species-Specific Amino Acid Difference in the Macaque CD4 Receptor Restricts Replication by Global Circulating HIV-1 Variants Representing Viruses from Recent Infection
Authors: Humes Daryl , Emery Sandra , Laws Elizabeth , Overbaugh Julie 
Published: September 2012

ABSTRACT
HIV-1 replicates poorly in macaque cells, and this had hindered the advancement of relevant nonhuman primate model systems for HIV-1 infection and pathogenesis. Several host restriction factors have been identified that contribute to this species-specific restriction to HIV-1 replication, but these do not fully explain the poor replication of most strains of HIV-1 in macaque cells. Only select HIV-1 envelope variants, typically those derived from viruses that have been adapted in cell culture, result in infectious chimeric SIVs encoding HIV-1 envelope (SHIVs). Here we demonstrate that most circulating HIV-1 variants obtained directly from infected individuals soon after virus acquisition do not efficiently mediate entry using the macaque CD4 receptor. The infectivity of these viruses is ca. 20- to 50-fold lower with the rhesus and pig-tailed macaque versus the human CD4 receptor. In contrast, culture-derived HIV-1 envelope variants that facilitate efficient replication in macaques showed similar infectivity with macaque and human CD4 receptors (within ∼2-fold). The ability of an envelope to mediate entry using macaque CD4 correlated with its ability to mediate entry of cells expressing low levels of the human CD4 receptor and with soluble CD4 sensitivity. Species-specific differences in the functional capacity of the CD4 receptor to mediate entry mapped to a single amino acid difference at position 39 that is under strong positive selection, suggesting that the evolution of CD4 may have been influenced by its function as a viral receptor. These results also suggest that N39 in human CD4 may be a critical residue for interaction of transmitted HIV-1 variants. These studies provide important insights into virus-host cell interactions that have hindered the development of relevant nonhuman primate models for HIV-1 infection and provide possible markers, such as sCD4 sensitivity, to identify potential HIV-1 variants that could be exploited for development of better SHIV/macaque model systems.
Reconstruction of the 1918 Influenza Virus: Unexpected Rewards from the Past
Authors: Taubenberger Jeffery K. , Baltimore David , Doherty Peter C. , Markel Howard , Morens David M. , Webster Robert G. , Wilson Ian A. 
Published: September 2012

ABSTRACTThe influenza pandemic of 1918–1919 killed approximately 50 million people. The unusually severe morbidity and mortality associated with the pandemic spurred physicians and scientists to isolate the etiologic agent, but the virus was not isolated in 1918. In 1996, it became possible to recover and sequence highly degraded fragments of influenza viral RNA retained in preserved tissues from several 1918 victims. These viral RNA sequences eventually permitted reconstruction of the complete 1918 virus, which has yielded, almost a century after the deaths of its victims, novel insights into influenza virus biology and pathogenesis and has provided important information about how to prevent and control future pandemics.
“Listening In” on How a Bacterium Takes Over the Plant Vascular System
Authors: Vinatzer Boris A. 
Published: September 2012

ABSTRACT

Bacteria that infect the plant vascular system are among the most destructive kind of plant pathogens because pathogen proliferation in the vascular system will sooner or later shut down the plant’s water and nutrient supply and necessarily lead to wilting and, in the worst case, death of the entire plant. How bacterial plant pathogens adapted to life in the plant vascular system is still poorly understood. As described in a recent article, Caitilyn Allen and her group studied the archetypical vascular pathogen
Ralstonia solanacearum
, the causative agent of bacterial wilt disease in almost 200 crop and ornamental plant species, and they have described the results of a microarray analysis that allowed them to “listen in” on the pathogen’s sabotaging activity inside the plant [J. M. Jacobs et al.,

mBio
3(4):e00114-12, 2012

]. Besides gaining for the first time an almost complete picture of
R. solanacearum
gene expression during infection, this approach allowed revision of a wrong assumption about the activity of the pathogen’s type III secretion system during infection and uncovered the importance of sucrose as an energy source for vascular pathogens like
R. solanacearum
.
Acupuncture Improves Cognitive Deficits and Increases Neuron Density of the Hippocampus in Middle-Aged Samp8 Mice
Authors: Li Guomin , Zhang Xuezhu , Cheng Haiyan , Shang Xuemei , Xie Hui , Zhang Xin , Yu Jianchun , Han Jingxian 
Published: September 2012

Objectives To examine whether acupuncture could improve cognitive deficits and reduce the loss of neurons in mice models of ageing. Methods Male 7.5-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-resistant inbred strains 1 (SAMR1) were divided into four groups (n=15 per group): SAMP8 acupuncture group (Pa), SAMP8 non-acupuncture point control group (Pn), SAMP8 control group (Pc) and SAMR1 normal control group (Rc). The behaviours were examined by the Morris water maze test and the neuron density in the hippocampus was estimated by the optical fractionator technique. Results The Morris water maze test demonstrated that the cognitive deficits of SAMP8 mice were improved by acupuncture treatment. Neuronal loss was found in hippocampal regions CA1 (−24%), CA3 (−18%) and DG (−28%) of Pc compared with Rc. The neuron number in hippocampal CA3 and DG of the Pa group was significantly increased by therapeutic acupuncture compared with the Pc group. Conclusions Acupuncture improved the cognitive impairment of middle-aged SAMP8 mice which could be attributed to the reduced neuron loss in hippocampal regions CA3 and DG. These results suggest that reducing neuron loss in the hippocampus by acupuncture is a potential therapeutic approach for the treatment of Alzheimer's disease and cognitive impairment diseases.
Cohort study of the association of hypnotic use with mortality in postmenopausal women
Authors: Hartz Arthur , Ross John Jacob 
Published: September 2012

ObjectivePrevious studies found an association between hypnotic use and mortality risk. The prospective outcome data and the many baseline risk factors included in the Women's Health Initiative (WHI) provide an opportunity to better understand the reasons for this association.SettingThe WHI is a long-term national health study that focused on strategies for preventing disease in postmenopausal women. Participants were enrolled from 1993 to 1998.DesignBaseline hypnotic use was evaluated for an association with subsequent mortality or disease after adjusting for baseline risk.Subjects148 938 postmenopausal women between the ages of 50 and 79 throughout the USA. The median follow-up was 8 years.Main outcome measuresMortality. Secondary outcomes included myocardial infarction, stroke, diabetes and seven types of cancer.ResultsFor persons who use hypnotic medications almost daily the age-adjusted hazard ratio (HR) for mortality was 1.62 (95% CI 1.50 to 1.74). Greater hypnotic use was associated with less healthy levels of physical function, general health and smoking at baseline. After adjustment for these factors the HR for almost daily hypnotic use was 1.14 (1.06 to 1.23) for mortality and 1.53 (1.18 to 1.99) for melanoma; it was not significantly associated with increased incidence of other diseases tested. Less frequent hypnotic use and several types of sleeping difficulties were not associated with mortality, but sleeping more than 10 h a night had a risk-adjusted HR for mortality of 1.28 (1.01 to 1.61).ConclusionsThe association of hypnotic use with mortality and incident disease was greatly reduced after adjusting for baseline risk factors. These findings do not support a strong independent association of hypnotic use with most health outcomes.
OP19 Social Networks and Depressive Symptoms in Russia, Poland and the Czech Republic: Evidence from the Hapiee Study
Authors: Franchi M , Pikhart H , Bobak M , Kubinova R , Malyutina S , Croezen S 
Published: September 2012

BackgroundIn countries of Central and Eastern Europe, prevalence rates of depressive symptoms are as high as 20% in men and 40% in women. Inclusion in social networks has been found to be a strong predictor of depressive symptoms in other countries, but little research on this association has been carried out in Central and Eastern Europe. This study aims to examine this association in the adult urban population in Russia, Poland and the Czech Republic.MethodsCross-sectional analysis was performed on baseline data (2002–2005) from the Health Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) study, involving men and women aged 45–69 from the adult urban population of the three countries of interest (Total N=25,674). Depressive symptoms were measured by the Centre for Epidemiological Studies Depression (CESD–20) scale. Inclusion in social networks was measured in terms of trust in informal or formal networks, and frequency of contacts with friends and distant relatives.ResultsIn Russia and the Czech Republic, odds of depressive symptoms were higher for men (Russia, OR 3.94, 95%CI 2.37–6.54; Czech Republic OR 2.04, 95%CI 1.18–3.52) and women (Russia, OR 2.19, 95%CI 1.47–2.99; Czech Republic OR 1.87, 95%CI 1.10–3.16) who had nobody to rely upon, compared with those who relied on friends or family. The pattern of association between frequency of contact with distant relatives or friends and depressive symptoms varied according to gender and country of origin of participants. Not having relatives outside the household was predictive of depressive symptoms among Polish men (OR 1.54, 95% C.I. 1.10–2.15) and women (OR 2.01, 95% C.I. 1.36–2.97); and not having any friends was associated with higher odds of depressives symptoms among Russian women (OR 1.54, 95% C.I. 1.09–2.19), and Polish men (OR 1.60, 95% C.I. 1.15–2.22).ConclusionThe results presented here suggest that exclusion from social networks is a strong predictor of depressive symptoms and that there is a country specific pattern of variation in how frequency of contact with social networks affects the risk of depressive symptoms. We argue that this variation could be due to differences in economic development and social capital of Russia, Poland and the Czech Republic.