bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unique Mutational Patterns in the Envelope α2 Amphipathic Helix and Acquisition of Length in gp120 Hypervariable Domains Are Associated with Resistance to Autologous Neutralization of Subtype C Human Immunodeficiency Virus Type 1
Authors: Rong Rong , Gnanakaran S. , Decker Julie M. , Bibollet-Ruche Frederic , Taylor Jesse , Sfakianos Jeffrey N. , Mokili John L. , Muldoon Mark , Mulenga Joseph , Allen Susan , Hahn Beatrice H. , Shaw George M. , Blackwell Jerry L. , Korber Bette T. , Hunter Eric , Derdeyn Cynthia A. 
Published: March 2007

ABSTRACT

Autologous neutralizing antibodies (NAb) against human immunodeficiency virus type 1 generate viral escape variants; however, the mechanisms of escape are not clearly defined. In a previous study, we determined the susceptibilities of 48 donor and 25 recipient envelope (Env) glycoproteins from five subtype C heterosexual transmission pairs to NAb in donor plasma by using a virus pseudotyping assay, thereby providing an ideal setting to probe the determinants of susceptibility to neutralization. In the present study, acquisition of length in the Env gp120 hypervariable domains was shown to correlate with resistance to NAb in donor plasma (
P
= 0.01; Kendall's tau test) but not in heterologous plasma. Sequence divergence in the gp120 V1-to-V4 region also correlated with resistance to donor (
P
= 0.0002) and heterologous (
P
= 0.001) NAb. A mutual information analysis suggested possible associations of nine amino acid positions in V1 to V4 with NAb resistance to the donor's antibodies, and five of these were located within an 18-residue amphipathic helix (α2) located on the gp120 outer domain. High nonsynonymous-to-synonymous substitution (dN/dS) ratios, indicative of positive selection, were also found at these five positions in subtype C sequences in the database. Nevertheless, exchange of the entire α2 helix between resistant donor Envs and sensitive recipient Envs did not alter the NAb phenotype. The combined mutual information and dN/dS analyses suggest that unique mutational patterns in α2 and insertions in the V1-to-V4 region are associated with NAb resistance during subtype C infection but that the selected positions within the α2 helix must be linked to still other changes in Env to confer antibody escape. These findings suggest that subtype C viruses utilize mutations in the α2 helix for efficient viral replication and immune avoidance.
Entry of Duck Hepatitis B Virus into Primary Duck Liver and Kidney Cells after Discovery of a Fusogenic Region within the Large Surface Protein
Authors: Maenz Claudia , Chang Shau-Feng , Iwanski Alicja , Bruns Michael 
Published: March 2007

ABSTRACT
Hepatitis B viruses exhibit a narrow host range specificity that is believed to be mediated by a domain of the large surface protein, designated L. For duck hepatitis B virus, it has been shown that the pre-S domain of L binds to carboxypeptidase D, a cellular receptor present in many species on a wide variety of cell types. Nonetheless, only hepatocytes become infected. It has remained vague which viral features determine host range specificity and organotropicity. By using chymotrypsin to treat duck hepatitis B virus, we addressed the question of whether a putative fusogenic region within the amino-terminal end of the small surface protein may participate in viral entry and possibly constitute one of the determinants of the host range of the virus. Addition of the enzyme to virions resulted in increased infectivity. Remarkably, even remnants of enzyme-treated subviral particles proved to be inhibitory to infection. A noninfectious deletion mutant devoid of the binding region for carboxypeptidase D could be rendered infectious for primary duck hepatocytes by treatment with chymotrypsin. Although because of the protease treatment mutant and wild-type viruses may have become infectious in an unspecific and receptor-independent manner, their host range specificity was not affected, as shown by the inability of the virus to replicate in different hepatoma cell lines, as well as primary chicken hepatocytes. Instead, the organotropicity of the virus could be reduced, which was demonstrated by infection of primary duck kidney cells.
Allelic Variation in the Hepatitis C Virus NS4B Protein Dramatically Influences RNA Replication
Authors: Blight Keril J. 
Published: March 2007

ABSTRACT

In the Huh-7.5 hepatoma cell line, replication of the genotype 1a H77 strain of hepatitis C virus (HCV) is attenuated compared to that of the genotype 1b Con1 strain. This study identifies the poorly characterized integral membrane protein, NS4B, as a major determinant for this replication difference. Chimeric H77 subgenomic replicons containing the entire NS4B gene from Con1 in place of the H77 NS4B sequence replicated approximately 10-fold better than the H77 parent and to levels similar to that of the adapted Con1 replicon. An intermediate level of replication enhancement was conferred by H77 chimeras containing the poorly conserved N-terminal 47 residues or the remaining less-divergent C terminus of Con1 NS4B. The replication-enhancing activity within the N terminus of NS4B was further mapped to two Con1-specific amino acids. Experiments to elucidate the mechanism of enhanced H77 replication revealed that Con1 NS4B primarily increased H77 RNA synthesis on a per cell basis, as indicated by the similar capacities of chimeric and parental replicons to establish replication in Huh-7.5 cells and the higher levels of both positive- and negative-strand RNAs for the chimeras than for the H77 parent. Additionally, enhanced H77 replication was not the result of Con1 NS4B-mediated effects on HCV translation efficiency or alterations in polyprotein processing. Expression of Con1 NS4B in
trans
did not improve the replication of the H77 parental replicon, suggesting a
cis
-dominant role for NS4B in HCV replication. These results provide the first evidence that allelic variation in the NS4B sequence between closely related isolates significantly impacts HCV replication in cell culture.
Old World and Clade C New World Arenaviruses Mimic the Molecular Mechanism of Receptor Recognition Used by α-Dystroglycan's Host-Derived Ligands
Authors: Rojek Jillian M. , Spiropoulou Christina F. , Campbell Kevin P. , Kunz Stefan 
Published: March 2007

ABSTRACTα-Dystroglycan (DG) is an important cellular receptor for extracellular matrix (ECM) proteins and also serves as the receptor for Old World arenaviruses Lassa fever virus (LFV) and lymphocytic choriomeningitis virus (LCMV) and clade C New World arenaviruses. In the host cell, α-DG is subject to a remarkably complex pattern of O glycosylation that is crucial for its interactions with ECM proteins. Two of these unusual sugar modifications, protein O mannosylation and glycan modifications involving the putative glycosyltransferase LARGE, have recently been implicated in arenavirus binding. Considering the complexity of α-DG O glycosylation, our present study was aimed at the identification of the specific O-linked glycans on α-DG that are recognized by arenaviruses. As previously shown for LCMV, we found that protein O mannosylation of α-DG is crucial for the binding of arenaviruses of distinct phylogenetic origins, including LFV, Mobala virus, and clade C New World arenaviruses. In contrast to the highly conserved requirement for O mannosylation, more generic O glycans present on α-DG are dispensable for arenavirus binding. Despite the critical role ofO-mannosyl glycans for arenavirus binding under normal conditions, the overexpression of LARGE in cells deficient in O mannosylation resulted in highly glycosylated α-DG that was functional as a receptor for arenaviruses. Thus, modifications by LARGE but notO-mannosyl glycans themselves are most likely the crucial structures recognized by arenaviruses. Together, the data demonstrate that arenaviruses recognize the same highly conserved O-glycan structures on α-DG involved in ECM protein binding, indicating a strikingly similar mechanism of receptor recognition by pathogen- and host-derived ligands.
Hepatitis B Virus Splice-Generated Protein Induces T-Cell Responses in HLA-Transgenic Mice and Hepatitis B Virus-Infected Patients
Authors: Mancini-Bourgine Maryline , Bayard Florence , Soussan Patrick , Deng Qiang , Lone Yu-Chun , Kremsdorf Dina , Michel Marie-Louise 
Published: March 2007

ABSTRACTHepatitis B virus splice-generated protein (HBSP), encoded by a spliced hepatitis B virus RNA, was recently identified in liver biopsy specimens from patients with chronic active hepatitis B. We investigated the possible generation of immunogenic peptides by the processing of this protein in vivo. We identified a panel of potential epitopes in HBSP by using predictive computational algorithms for peptide binding to HLA molecules. We used transgenic mice devoid of murine major histocompatibility complex (MHC) class I molecules and positive for human MHC class I molecules to characterize immune responses specific for HBSP. Two HLA-A2-restricted peptides and one immunodominant HLA-B7-restricted epitope were identified following the immunization of mice with DNA vectors encoding HBSP. Most importantly, a set of overlapping peptides covering the HBSP sequence induced significant HBSP-specific T-cell responses in peripheral blood mononuclear cells from patients with chronic hepatitis B. The response was multispecific, as several epitopes were recognized by CD8+and CD4+human T cells. This study provides the first evidence that this protein generated in vivo from an alternative reading frame of the hepatitis B virus genome activates T-cell responses in hepatitis B virus-infected patients. Given that hepatitis B is an immune response-mediated disease, the detection of T-cell responses directed against HBSP in patients with chronic hepatitis B suggests a potential role for this protein in liver disease progression.
Physical and Functional Interactions of Human Endogenous Retrovirus Proteins Np9 and Rec with the Promyelocytic Leukemia Zinc Finger Protein
Authors: Denne Miriam , Sauter Marlies , Armbruester Vivienne , Licht Jonathan D. , Roemer Klaus , Mueller-Lantzsch Nikolaus 
Published: March 2007

ABSTRACT

Only few of the human endogenous retrovirus (HERV) sequences in the human genome can produce proteins. We have previously reported that (i) patients with germ cell tumors often make antibodies against proteins encoded by HERV-K elements, (ii) expression of the HERV-K
rec
gene in transgenic mice can interfere with germ cell development and induce carcinoma in situ, and (iii) HERV-K
np9
transcript is overproduced in many tumors including breast cancers. Here we document that both Np9 and Rec physically and functionally interact with the promyelocytic leukemia zinc finger (PLZF) tumor suppressor, a transcriptional repressor and chromatin remodeler implicated in cancer and the self-renewal of spermatogonial stem cells. Interaction is mediated via two different central and C-terminal domains of Np9 and Rec and the C-terminal zinc fingers of PLZF. One major target of PLZF is the c-
myc
proto-oncogene. Coexpression of Np9 and Rec with PLZF abrogates the transcriptional repression of the c-
myc
gene promoter by PLZF and results in c-Myc overproduction, altered expression of c-Myc-regulated genes, and corresponding effects on cell proliferation and survival. Thus, the human endogenous retrovirus proteins Np9 and Rec may act oncogenically by derepressing c-
myc
through the inhibition of PLZF.
The Genome of
Gryllus bimaculatus
Nudivirus Indicates an Ancient Diversification of Baculovirus-Related Nonoccluded Nudiviruses of Insects
Authors: Wang Yongjie , Kleespies Regina G. , Huger Alois M. , Jehle Johannes A. 
Published: March 2007

ABSTRACT

The
Gryllus bimaculatus
nudivirus (GbNV) infects nymphs and adults of the cricket
Gryllus bimaculatus
(Orthoptera: Gryllidae). GbNV and other nudiviruses such as
Heliothis zea
nudivirus 1 (HzNV-1) and
Oryctes rhinoceros
nudivirus (OrNV) were previously called “nonoccluded baculoviruses” as they share some similar structural, genomic, and replication aspects with members of the family
Baculoviridae
. Their relationships to each other and to baculoviruses are elucidated by the sequence of the complete genome of GbNV, which is 96,944 bp, has an AT content of 72%, and potentially contains 98 predicted protein-coding open reading frames (ORFs). Forty-one ORFs of GbNV share sequence similarities with ORFs found in OrNV, HzNV-1, baculoviruses, and bacteria. Most notably, 15 GbNV ORFs are homologous to the baculovirus core genes, which are associated with transcription (
lef
-
8
,
lef
-
9
,
lef
-
4
,
vlf
-
1
, and
lef-5
), replication (
dnapol
), structural proteins (
p74
,
pif
-
1
,
pif
-
2
,
pif
-
3
,
vp91
, and
odv-e56
), and proteins of unknown function (
38K
,
ac81
, and
19kda
). Homologues to these baculovirus core genes have been predicted in HzNV-1 as well. Six GbNV ORFs are homologous to nonconserved baculovirus genes
dnaligase
,
helicase 2
,
rr1
,
rr2
,
iap
-
3
, and
desmoplakin
. However, the remaining 57 ORFs revealed no homology or poor similarities to the current gene databases. No homologous repeat (
hr
) sequences but fourteen short direct repeat (
dr
) regions were detected in the GbNV genome. Gene content and sequence similarity suggest that the nudiviruses GbNV, HzNV-1, and OrNV form a monophyletic group of nonoccluded double-stranded DNA viruses, which separated from the baculovirus lineage before this radiated into dipteran-, hymenopteran-, and lepidopteran-specific clades of occluded nucleopolyhedroviruses and granuloviruses. The accumulated information on the GbNV genome suggests that nudiviruses form a highly diverse and phylogenetically ancient sister group of the baculoviruses, which have evolved in a variety of highly divergent host orders.
Intraretinal Transplantation for Rod‐Cell Replacement in Light‐Damaged Retinas
Authors: del Cerro Manuel , Notter Mary F. D. , del Cerro Coca , Wiegand Stanley J. , Grover Donald A. , Lazar Eliot 
Published: March 2007

Blindness from retinal disease is often the consequence of extensive damage to the photoreceptor cell population, while other cell types which form the neural retina are relatively spared. In this setting, transplantation of photoreceptor cells could offer hope for the restoration of some degree of visual function. We testd the feasibility of this approach by transplanting immature retinal cells into the eyes of adult rats affected by late stage phototoxic retinopathy, which are almost totally devoid of photoreceptor cells.Dissociated neuroretinal cells from newborn rats were injected into the hosts′ retinas. These cells were labelled with the fluorescent tracer Fast‐blue for identification within the host eye. Survival time ranged from 3 to 100 post‐transplantation days.Fundus examination of light‐irradiated eyes showed pallor caused by a considerable reduction of the retino‐choroidal vascular bed after light irradiation. Histologically the hosts exhibited decimation of the elements forming the outer layers.throughout the entire retina.As visualized by light and electron microscopic procedures, we report the differentiation of clusters of transplanted photoreceptor cells, and the integration of these cells within the adjacent areas of the host retina.Fluorescence microscopy showed these clusters to be formed by fluorescently labelled cells developing in intimate contact with the unlabelled host retina. Electron microscopically it was possible to determine that these photoreceptors had established synaptic contacts. These observations indicate that successful transplantation of immature retinal cells is feasible into adult eyes that have suffered extensive retino‐choroidal damage. These findings also support the concept that retinal transplantation is a procedure which may open new avenues into the study of retinal repair.
Supranumerary Barrels Develop in the Somatosensory Cortex of Mice, After the Implantation of the Vibrissal Follicle Parts Containing Large Numbers of Receptors
Authors: Andrés F. L. 
Published: March 2007

In the mouse whiskerpad there is a group of vibrissal follicles arranged in five rows, which are topologically represented in the contralateral somatosensory cortex by the barrelfield.Each vibrissal follicle is a specialized sensory organ containing a large number of receptors, mostly Merkel cells.In these experiments, the parts of the vibrissal follicles containing most of the receptors were transplanted
to different regions of the whiskerpad of newborn mice, to know whether “new”, supranumerary barrels could develop.The results confirm this hypothesis. However, the “new” barrels are not topologically represented in the barrelfield, as normal barrels do.
Electrophysiological and Morphological Properties of Embryonic Neocortical Grafts Developing in Different Regions of the Host Rat Brain
Authors: Senatorov V. V. , Obuhova G. P. , Fülöp Z. 
Published: March 2007

Parallel morphological and electrophysiological studies of embryonic neocortical tissue (primordia of anterior parietal–presumptive sensorimotor–cortex) grafted into different regions of the host adult brain (sensori‐motor cortex, caudate‐putamen, septum or thalamus) were carried out to investigate to what extent the properties of transplanted embryonic neocortex–an advanced organizational form of neuronal tissue–are affected by homotopic or heterotopic surroundings.The results point to the importance of the host tissue environment as it influences both the size, the morphological and functional properties of the implanted embryonic cortical plate tissue. The cortical grafts were smaller in size when developed homo‐topically in sensorimotor cortex and grew larger in heterotopic environment (caudate‐putamen, septum, thalamus). The orientation of neuronal dendrites in the grafts tends to follow that seen in the surroundings. The homotopic grafts showed a better structural integration into the host brain. Differences were seen between intracortical and subcortical transplants in the spontaneous firing rate of neurons and in the ratio of units with various types of spontaneous discharge.
Transplantation of Fetal CNS Tissue Into the Peripheral Nervous System:A Model to Study Aberrant Changes in the Neuronal Cytoskeleton
Authors: Doering Laurie C. 
Published: March 2007

Defined regions (septum, substantia nigra) of the embryonic central nervous system (CNS) were transplanted into the sciatic nerves of young adult rats. Immunocytochemical techniques were used to examine the expression of neurotransmitter related enzymes and neuronal cytoskeletal proteins in the grafts.The origin of the septal grafts was confirmed by immunoreactivity in nenrons to choline acetyltransferase and the β‐nerve growth factor receptor (192‐IgG). In substantia nigra grafts, neuronal perikarya and processes were identified with an antibody directed against tyrosine hydroxylase. Typical spatial distributions of phosphorylated (Mr 200,000)
and non phosphorylated (Mr 168,000 & 200,000) neurofilaments were observed in the short term (1‐2 months) grafts with the monoclonal antibodies RT97 and SMI‐32 respectively. Dense dendrite arbors and neuronal cell bodies were immunostained with an antibody that recognizes a high molecular weight microtubule associated protein (MAP2).In the long term (1 year) transplants, prominent cytoskeletal changes in the somata, axons and dendrites of neurons were evident. The cells showed a shift in phosphorylated neurofilament staining from the axon to the soma accompanied by a reduction in axonal immunoreactivity in the adjacent neuropil, Other abnormal features included swollen perikarya, hypertrophied axonal segments and Short segments of kinked axons. Regression of the dendrite trees in the long standing grafts was also apparent when sections were reacted with the MAP2 antibody.These experiments indicate that grafted fetal neurons, isolated in the peripheral nervous system, differentiate and express markers like their counterparts in situ. After extended time periods under these circumstances, cytoskeletal modifications become apparent in the neurons. These aberrant changes are similar to morphological characteristics associated with aging and neurodegenerative disorders. This experimental paradigm offers a new approach, to study cytoskeletal disturbances in neurons and provides a unique opportunity to examine conditions that
may modulate the abnormal changes.
Motor Deficits Are Produced By Removing Some Cortical TransplantsGrafted Into Injured Sensorimotor Cortexof Neonatal Rats
Authors: Sandor Rick , Gonzalez Manuel F. , Moseley Michael , Sharp Frank R. 
Published: March 2007

Fetal frontal cortex was transplanted into cavities formed in the right, motor cortex of neonatal rats. As adults, the animals were trained to press two levers in rapid succession with their left forelimb to receive food rewards. Once they had reached an optimal level of performance, the effect of removing their transplants was assessed. Surgical removal of transplants significantly impaired the performance of 2 of 4 subjects. Placing a crossstrain skin graft to induce the immunological rejection of the transplants produced a behavioral deficit in 1 of 2 subjects with complete transplant removal. Skin grafts produced no behavioral effects in four subjects that had surviving transplants. Since the motor deficit produced by transplant removal resembled those observed following the removal of normal motor cortex, we propose that these three transplants functioned within the host brain.Histology Showed that the procedures used to remove cortical grafts did not injure any host brains. Therefore, host brain damage is unlikely to account for the behavioral deterioration that followed transplant removals.
Viable Adrenal Medullary Transplants in Non‐Human Primates: Increasing the Number of Grafts
Authors: Dubach Mark 
Published: March 2007

The robust survival of stereotaxic adrenal
medullary autografts in monkey brain parenchyma
depends heavily on technique/11/. One
aspect of technique critical for clinical applications
of CNS grafting is the problem of spreading
treatment effects throughout large regions in a
primate brain. Stereotaxic placement of a large
number of grafts, which would address this problem,
would require that later grafts retain the
capacity for viability over a long period of time
during the surgery, while earlier grafts are being
made. In the present experiments involving 12
longtailed macaques (Macaca fascicularis), some
grafts remained in medium 2.5 h before being
transplanted, without apparent loss of viability.clinically sufficient distribution of graft tissue
would also require a large number of separate
grafts to be derived from one adrenal medulla.
One method for subdividing the gland might be to
cut it into numerous very small pieces, but various
dicing techniques described in this report
have yielded little viable graft tissue. On the
other hand, the number of ribbon grafts of the
original dimensions available from a single gland
is rather small; adrenal ribbons of the original
dimensions were therefore further dissected.
Half‐length and half‐width ribbons were successful,
but less so than full‐size ribbons in terms of
proportionate viability. An assay of behavioral
effectiveness, applied to all subjects described
here, is presented in a separate contribution/9/.