bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stabilization of renal function after the first year of follow‐up in kidney transplant recipients treated for significant BK polyomavirus infection or BK polyomavirus‐associated nephropathy
Authors: Simard‐Meilleur Marie‐Christine , Bodson‐Clermont Paule , St‐Louis Gilles , Pâquet Michel R. , Girardin Catherine , Fortin Marie‐Chantal , Cardinal Héloïse , Hébert Marie‐Josée , Lévesque Renée , Renoult Edith 
Published: February 2017

AbstractBackgroundBK polyomavirus virus (BKPyV) screening and immunosuppression reduction effectively prevent graft loss due to BKPyV‐associated nephropathy (BKPVAN) during the first year after transplantation. The aim of our study was to evaluate the impact of this infection during longer follow‐up periods.MethodsWe reviewed the outcome of our screening and immunosuppression reduction protocol in 305 patients who received a kidney transplant between March 2008 and January 2013. Quantitative BKPyV DNA surveillance in plasma was performed at 1, 2, 3, 6, 9, and 12 months after transplantation. Patients with significant viremia and/or biopsy‐proven BKPVAN were treated with immunosuppression reduction and leflunomide.ResultsDuring the first post‐transplant year, 24 patients (7.9%) developed significant viremia at a median time of 95 days, and 18 patients had BKPVAN; 23 of the 24 (7.5%) were treated according to our protocol (group BKV+); 225 patients (73.8%) did not develop any BK viremia (group BKV−). Allograft function was similar in both groups at 1 month post transplantation (P=.87), but significantly worse at 1 year in the BKV+ group (P=.002). Thereafter, kidney function stabilized in the BKV+ group and no differences in patient and graft survival were seen between the groups after a median follow‐up of 4 years.ConclusionsWe confirm the early occurrence of BKPyV replication after transplantation and the short‐term decline in renal function. However, early detection of BKPyV replication, prompt diagnosis, and reduction in immunosuppression may offer long‐term benefits for graft function.
Are bilateral and multilateral aid‐for‐trade complementary?
Authors: Tadesse Bedassa , Shukralla Elias , Fayissa Bichaka 
Published: February 2017

AbstractUsing the first comprehensive estimates of ad valorem tariff equivalent bilateral trade costs spanning the time period 2002–10, we examine whether the aid‐for‐trade (AFT) inflows reduce bilateral trade costs facing aid recipients. If so, we ask whether the trade costs reduction effects of AFT from bilateral and multilateral sources are complementary. By showing the extent to which the observed trade cost reduction effects of AFT from bilateral (multilateral) sources correlate with the magnitudes of AFT disbursements from multilateral (bilateral) sources, we present plausible explanation for the cross‐country variations in the extent to which AFT promotes trade flows. Our findings have, thus, important policy implications for shaping future discourses on the coordination of disbursements for enhancing the effectiveness of AFT.
Discovery of Novel Pneumococcal Serotype 35D, a Natural WciG-Deficient Variant of Serotype 35B
Authors: Geno K. Aaron , Saad Jamil S. , Nahm Moon H. 
Published: February 2017

ABSTRACT

Pneumococcus (
Streptococcus pneumoniae
) remains a significant cause of morbidity and mortality, especially among those at the extremes of age. Its capsular polysaccharide is essential for systemic virulence. Over 90 serologically distinct pneumococcal capsular polysaccharides (serotypes) are recognized, but they are unequal in prevalence. Because antibodies against the capsule are protective, polysaccharide conjugate vaccines, which are constructed against the most prevalent serotypes, have caused great reductions in pneumococcal disease caused by these serotypes. In response, however, the relative prevalences of serotypes have shifted. Certain previously rare serotypes, such as serotype 35B, are increasing in prevalence. Serotype 35B is thus a likely future vaccine candidate, but due to their previous rarity, serotype 35B strains have not been scrutinized for underlying heterogeneity. We studied putative serotype 35B clinical isolates to assess the uniformity of their serological reactions. While most isolates exhibited the accepted serology of serotype 35B, one isolate failed to bind to critical serotyping reagents. We determined that the genetic basis for this aberrant serology was the presence of inactivating mutations in the
O
-acetyltransferase gene
wciG
. Complementation studies in a
wciG
deletion strain verified that the mutant WciG was nonfunctional, and the serology of the mutant could be restored through complementation with a construct encoding a functional WciG. Nuclear magnetic resonance studies confirmed that the capsule of the WciG-deficient isolate lacked
O
-acetylation but was otherwise identical to serotype 35B. As this isolate expresses a unique serology with unique biochemistry and a stable genetic basis, we named its novel capsule serotype 35D.
High Prevalence and Diversity of Hepatitis Viruses in Suspected Cases of Yellow Fever in the Democratic Republic of Congo
Authors: Makiala-Mandanda Sheila , Le Gal Frédéric , Ngwaka-Matsung Nadine , Ahuka-Mundeke Steve , Onanga Richard , Bivigou-Mboumba Berthold , Pukuta-Simbu Elisabeth , Gerber Athenaïs , Abbate Jessica L. , Mwamba Dieudonné , Berthet Nicolas , Leroy Eric Maurice , Muyembe-Tamfum Jean-Jacques , Becquart Pierre 
Published: February 2017

ABSTRACT

The majority of patients with acute febrile jaundice (>95%) identified through a yellow fever surveillance program in the Democratic Republic of Congo (DRC) test negative for antibodies against yellow fever virus. However, no etiological investigation has ever been carried out on these patients. Here, we tested for hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV) viruses, all of which can cause acute febrile jaundice, in patients included in the yellow fever surveillance program in the DRC. On a total of 498 serum samples collected from suspected cases of yellow fever from January 2003 to January 2012, enzyme-linked immunosorbent assay (ELISA) techniques were used to screen for antibodies against HAV (IgM) and HEV (IgM) and for antigens and antibodies against HBV (HBsAg and anti-hepatitis B core protein [HBc] IgM, respectively), HCV, and HDV. Viral loads and genotypes were determined for HBV and HVD. Viral hepatitis serological markers were diagnosed in 218 (43.7%) patients. The seroprevalences were 16.7% for HAV, 24.6% for HBV, 2.3% for HCV, and 10.4% for HEV, and 26.1% of HBV-positive patients were also infected with HDV. Median viral loads were 4.19 × 10
5
IU/ml for HBV (range, 769 to 9.82 × 10
9
IU/ml) and 1.4 × 10
6
IU/ml for HDV (range, 3.1 × 10
2
to 2.9 × 10
8
IU/ml). Genotypes A, E, and D of HBV and genotype 1 of HDV were detected. These high hepatitis prevalence rates highlight the necessity to include screening for hepatitis viruses in the yellow fever surveillance program in the DRC.
Towards a New Strategy for Diagnosis of Congenital Trypanosoma cruzi Infection
Authors: Abras Alba , Muñoz Carmen , Ballart Cristina , Berenguer Pere , Llovet Teresa , Herrero Mercedes , Tebar Silvia , Pinazo María-Jesús , Posada Elizabeth , Martí Carmen , Fumadó Victoria , Bosch Jordi , Coll Oriol , Juncosa Teresa , Ginovart Gemma , Armengol Josep , Gascón Joaquim , Portús Montserrat , Gállego Montserrat 
Published: February 2017

ABSTRACT

The immigration of Latin American women of childbearing age has spread the congenital transmission of Chagas disease to areas of nonendemicity, and the disease is now a worldwide problem. Some European health authorities have implemented screening programs to prevent vertical transmission, but the lack of a uniform protocol calls for the urgent establishment of a new strategy common to all laboratories. Our aims were to (i) analyze the trend of passive IgG antibodies in the newborn by means of five serological tests for the diagnosis and follow-up of congenital
Trypanosoma cruzi
infection, (ii) assess the utility of these techniques for diagnosing a congenital transmission, and (iii) propose a strategy for a prompt, efficient, and cost-effective diagnosis of
T. cruzi
infection. In noninfected newborns, a continuous decreasing trend of passive IgG antibodies was observed, but none of the serological assays seroreverted in any the infants before 12 months. From 12 months onwards, serological tests achieved negative results in all the samples analyzed, with the exception of the highly sensitive chemiluminescent microparticle immunoassay (CMIA). In contrast, in congenitally infected infants, the antibody decline was detected only after treatment initiation. In order to improve the diagnosis of congenital
T. cruzi
infection, we propose a new strategy involving fewer tests that allows significant cost savings. The protocol could start 1 month after birth with a parasitological test and/or a PCR. If negative, a serological test would be carried out at 9 months, which if positive, would be followed by another at around 12 months for confirmation.
Reactivity of Porcine Epidemic Diarrhea Virus Structural Proteins to Antibodies against Porcine Enteric Coronaviruses: Diagnostic Implications
Authors: Gimenez-Lirola Luis Gabriel , Zhang Jianqiang , Carrillo-Avila Jose Antonio , Chen Qi , Magtoto Ronaldo , Poonsuk Korakrit , Baum David H. , Piñeyro Pablo , Zimmerman Jeffrey 
Published: February 2017

ABSTRACT

The development of porcine epidemic diarrhea virus (PEDV) antibody-based assays is important for detecting infected animals, confirming previous virus exposure, and monitoring sow herd immunity. However, the potential cross-reactivity among porcine coronaviruses is a major concern for the development of pathogen-specific assays. In this study, we used serum samples (
n
= 792) from pigs of precisely known infection status and a multiplex fluorescent microbead-based immunoassay and/or enzyme-linked immunoassay platform to characterize the antibody response to PEDV whole-virus (WV) particles and recombinant polypeptides derived from the four PEDV structural proteins, i.e., spike (S), nucleocapsid (N), membrane (M), and envelope (E). Antibody assay cutoff values were selected to provide 100% diagnostic specificity for each target. The earliest IgG antibody response, mainly directed against S1 polypeptides, was observed at days 7 to 10 postinfection. With the exception of nonreactive protein E, we observed similar antibody ontogenies and patterns of seroconversion for S1, N, M, and WV antigens. Recombinant S1 provided the best diagnostic sensitivity, regardless of the PEDV strain, with no cross-reactivity detected against transmissible gastroenteritis virus (TGEV), porcine respiratory coronavirus (PRCV), or porcine deltacoronavirus (PDCoV) pig antisera. The WV particles showed some cross-reactivity to TGEV Miller and TGEV Purdue antisera, while N protein presented some cross-reactivity to TGEV Miller. The M protein was highly cross-reactive to TGEV and PRCV antisera. Differences in the antibody responses to specific PEDV structural proteins have important implications in the development and performance of antibody assays for the diagnosis of PEDV enteric disease.
JAK-STAT Signaling Pathways and Inhibitors Affect Reversion of Envelope-Mutated HIV-1
Authors: Quan Yudong , Xu Hongtao , Han Yingshan , Mesplède Thibault , Wainberg Mark A. 
Published: February 2017

ABSTRACT
HIV can spread by both cell-free and cell-to-cell transmission. Here, we show that many of the amino acid changes in Env that are close to the CD4 binding pocket can affect HIV replication. We generated a number of mutant viruses that were unable to infect T cells as cell-free viruses but were nevertheless able to infect certain T cell lines as cell-associated viruses, which was followed by reversion to the wild type. However, the activation of JAK-STAT signaling pathways caused the inhibition of such cell-to-cell infection as well as the reversion of multiple HIV Env mutants that displayed differences in their abilities to bind to the CD4 receptor. Specifically, two T cell activators, interleukin-2 (IL-2) and phorbol 12-myristate 13-acetate (PMA), both capable of activation of JAK-STAT pathways, were able to inhibit cell-to-cell viral transmission. In contrast, but consistent with the above result, a number of JAK-STAT and mTOR inhibitors actually promoted HIV-1 transmission and reversion. Hence, JAK-STAT signaling pathways may differentially affect the replication of a variety of HIV Env mutants in ways that differ from the role that these pathways play in the replication of wild-type viruses.

IMPORTANCE
Specific alterations in HIV Env close to the CD4 binding site can differentially change the ability of HIV to mediate infection for cell-free and cell-associated viruses. However, such differences are dependent to some extent on the types of target cells used. JAK-STAT signaling pathways are able to play major roles in these processes. This work sheds new light on factors that can govern HIV infection of target cells.
The Viral Gene ORF79 Encodes a Repressor Regulating Induction of the Lytic Life Cycle in the Haloalkaliphilic Virus ϕCh1
Authors: Selb Regina , Derntl Christian , Klein Reinhard , Alte Beatrix , Hofbauer Christoph , Kaufmann Martin , Beraha Judith , Schöner Léa , Witte Angela 
Published: February 2017

ABSTRACT

In this study, we describe the construction of the first genetically modified mutant of a halovirus infecting haloalkaliphilic
Archaea
. By random choice, we targeted ORF79, a currently uncharacterized viral gene of the haloalkaliphilic virus ϕCh1. We used a polyethylene glycol (PEG)-mediated transformation method to deliver a disruption cassette into a lysogenic strain of the haloalkaliphilic archaeon
Natrialba magadii
bearing ϕCh1 as a provirus. This approach yielded mutant virus particles carrying a disrupted version of ORF79. Disruption of ORF79 did not influence morphology of the mature virions. The mutant virus was able to infect cured strains of
N. magadii
, resulting in a lysogenic, ORF79-disrupted strain. Analysis of this strain carrying the mutant virus revealed a repressor function of ORF79. In the absence of gp79, onset of lysis and expression of viral proteins occurred prematurely compared to their timing in the wild-type strain. Constitutive expression of ORF79 in a cured strain of
N. magadii
reduced the plating efficiency of ϕCh1 by seven orders of magnitude. Overexpression of ORF79 in a lysogenic strain of
N. magadii
resulted in an inhibition of lysis and total absence of viral proteins as well as viral progeny. In further experiments, gp79 directly regulated the expression of the tail fiber protein ORF34 but did not influence the methyltransferase gene ORF94. Further, we describe the establishment of an inducible promoter for
in vivo
studies in
N. magadii
.

IMPORTANCE
Genetic analyses of haloalkaliphilic
Archaea
or haloviruses are only rarely reported. Therefore, only little insight into the
in vivo
roles of proteins and their functions has been gained so far. We used a reverse genetics approach to identify the function of a yet undescribed gene of ϕCh1. We provide evidence that gp79, a currently unknown protein of ϕCh1, acts as a repressor protein of the viral life cycle, affecting the transition from the lysogenic to the lytic state of the virus. Thus, repressor genes in other haloviruses could be identified by sequence homologies to gp79 in the future. Moreover, we describe the use of an inducible promoter of
N. magadii
. Our work provides valuable tools for the identification of other unknown viral genes by our approach as well as for functional studies of proteins by inducible expression.
Inhibition of Vpx-Mediated SAMHD1 and Vpr-Mediated Host Helicase Transcription Factor Degradation by Selective Disruption of Viral CRL4 (DCAF1) E3 Ubiquitin Ligase Assembly
Authors: Wang Hong , Guo Haoran , Su Jiaming , Rui Yajuan , Zheng Wenwen , Gao Wenying , Zhang Wenyan , Li Zhaolong , Liu Guanchen , Markham Richard B. , Wei Wei , Yu Xiao-Fang 
Published: February 2017

ABSTRACT

The lentiviral accessory proteins Vpx and Vpr are known to utilize CRL4 (DCAF1) E3 ligase to induce the degradation of the host restriction factor SAMHD1 or host helicase transcription factor (HLTF), respectively. Selective disruption of viral CRL4 (DCAF1) E3 ligase could be a promising antiviral strategy. Recently, we have determined that posttranslational modification (neddylation) of Cullin-4 is required for the activation of Vpx-CRL4 (DCAF1) E3 ligase. However, the mechanism of Vpx/Vpr-CRL4 (DCAF1) E3 ligase assembly is still poorly understood. Here, we report that zinc coordination is an important regulator of Vpx-CRL4 E3 ligase assembly. Residues in a conserved zinc-binding motif of Vpx were essential for the recruitment of the CRL4 (DCAF1) E3 complex and Vpx-induced SAMHD1 degradation. Importantly, altering the intracellular zinc concentration by treatment with the zinc chelator
N
,
N
,
N
′-tetrakis-(2′-pyridylmethyl)ethylenediamine (TPEN) potently blocked Vpx-mediated SAMHD1 degradation and inhibited wild-type SIVmac (simian immunodeficiency virus of macaques) infection of myeloid cells, even in the presence of Vpx. TPEN selectively inhibited Vpx and DCAF1 binding but not the Vpx-SAMHD1 interaction or Vpx virion packaging. Moreover, we have shown that zinc coordination is also important for the assembly of the HIV-1 Vpr-CRL4 E3 ligase. In particular, Vpr zinc-binding motif mutation or TPEN treatment efficiently inhibited Vpr-CRL4 (DCAF1) E3 ligase assembly and Vpr-mediated HLTF degradation or Vpr-induced G
2
cell cycle arrest. Collectively, our study sheds light on a conserved strategy by the viral proteins Vpx and Vpr to recruit host CRL4 (DCAF1) E3 ligase, which represents a target for novel anti-human immunodeficiency virus (HIV) drug development.

IMPORTANCE
The Vpr and its paralog Vpx are accessory proteins encoded by different human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) lentiviruses. To facilitate viral replication, Vpx has evolved to induce SAMHD1 degradation and Vpr to mediate HLTF degradation. Both Vpx and Vpr perform their functions by recruiting CRL4 (DCAF1) E3 ligase. In this study, we demonstrate that the assembly of the Vpx- or Vpr-CRL4 E3 ligase requires a highly conserved zinc-binding motif. This motif is specifically required for the DCAF1 interaction but not for the interaction of Vpx or Vpr with its substrate. Selective disruption of Vpx- or Vpr-CRL4 E3 ligase function was achieved by zinc sequestration using
N
,
N
,
N
′-tetrakis-(2′-pyridylmethyl)ethylenediamine (TPEN). At the same time, zinc sequestration had no effect on zinc-dependent cellular protein functions. Therefore, information obtained from this study may be important for novel anti-HIV drug development.
Relationship between Measures of HIV Reactivation and Decline of the Latent Reservoir under Latency-Reversing Agents
Authors: Petravic Janka , Rasmussen Thomas A. , Lewin Sharon R. , Kent Stephen J. , Davenport Miles P. 
Published: February 2017

ABSTRACT
Antiretroviral-free HIV remission requires substantial reduction of the number of latently infected cells and enhanced immune control of viremia. Latency-reversing agents (LRAs) aim to eliminate latently infected cells by increasing the rate of reactivation of HIV transcription, which exposes these cells to killing by the immune system. As LRAs are explored in clinical trials, it becomes increasingly important to assess the effect of an increased HIV reactivation rate on the decline of latently infected cells and to estimate LRA efficacy in increasing virus reactivation. However, whether the extent of HIV reactivation is a good predictor of the rate of decline of the number of latently infected cells is dependent on a number of factors. Our modeling shows that the mechanisms of maintenance and clearance of the reservoir, the life span of cells with reactivated HIV, and other factors may significantly impact the relationship between measures of HIV reactivation and the decline in the number of latently infected cells. The usual measures of HIV reactivation are the increase in cell-associated HIV RNA (CA RNA) and/or plasma HIV RNA soon after administration. We analyze two recent studies where CA RNA was used to estimate the impact of two novel LRAs, panobinostat and romidepsin. Both drugs increased the CA RNA level 3- to 4-fold in clinical trials. However, cells with panobinostat-reactivated HIV appeared long-lived (half-life > 1 month), suggesting that the HIV reactivation rate increased by approximately 8%. With romidepsin, the life span of cells that reactivated HIV was short (2 days), suggesting that the HIV reactivation rate may have doubled under treatment.

IMPORTANCE
Long-lived latently infected cells that persist on antiretroviral treatment (ART) are thought to be the source of viral rebound soon after ART interruption. The elimination of latently infected cells is an important step in achieving antiretroviral-free HIV remission. Latency-reversing agents (LRAs) aim to activate HIV expression in latently infected cells, which could lead to their death. Here, we discuss the possible impact of the LRAs on the reduction of the number of latently infected cells, depending on the mechanisms of their loss and self-renewal and on the life span of the cells that have HIV transcription activated by the LRAs.
Lateral Organization of Influenza Virus Proteins in the Budozone Region of the Plasma Membrane
Authors: Leser George P. , Lamb Robert A. 
Published: February 2017

ABSTRACTInfluenza virus assembles and buds at the plasma membrane of virus-infected cells. The viral proteins assemble at the same site on the plasma membrane for budding to occur. This involves a complex web of interactions among viral proteins. Some proteins, like hemagglutinin (HA), NA, and M2, are integral membrane proteins. M1 is peripherally membrane associated, whereas NP associates with viral RNA to form an RNP complex that associates with the cytoplasmic face of the plasma membrane. Furthermore, HA and NP have been shown to be concentrated in cholesterol-rich membrane raft domains, whereas M2, although containing a cholesterol binding motif, is not raft associated. Here we identify viral proteins in planar sheets of plasma membrane using immunogold staining. The distribution of these proteins was examined individually and pairwise by using the Ripley K function, a type of nearest-neighbor analysis. Individually, HA, NA, M1, M2, and NP were shown to self-associate in or on the plasma membrane. HA and M2 are strongly coclustered in the plasma membrane; however, in the case of NA and M2, clustering depends upon the expression system used. Despite both proteins being raft resident, HA and NA occupy distinct but adjacent membrane domains. M2 and M1 strongly cocluster, but the association of M1 with HA or NA is dependent upon the means of expression. The presence of HA and NP at the site of budding depends upon the coexpression of other viral proteins. Similarly, M2 and NP occupy separate compartments, but an association can be bridged by the coexpression of M1.IMPORTANCEThe complement of influenza virus proteins necessary for the budding of progeny virions needs to accumulate at budozones. This is complicated by HA and NA residing in lipid raft-like domains, whereas M2, although an integral membrane protein, is not raft associated. Other necessary protein components such as M1 and NP are peripherally associated with the membrane. Our data define spatial relationships between viral proteins in the plasma membrane. Some proteins, such as HA and M2, inherently cocluster within the membrane, although M2 is found mostly at the periphery of regions of HA, consistent with the proposed role of M2 in scission at the end of budding. The association between some pairs of influenza virus proteins, such as M2 and NP, appears to be brokered by additional influenza virus proteins, in this case M1. HA and NA, while raft associated, reside in distinct domains, reflecting their distributions in the viral membrane.