bluuebunny/crossref_metadata_2025_split huggingface dataset:
Herpes Simplex Virus Type 1 Latency-Associated Transcript Expression Protects Trigeminal Ganglion Neurons from Apoptosis
Authors: Branco Francisco J. , Fraser Nigel W. 
Published: July 2005

ABSTRACT

Upon infection of murine trigeminal ganglia with herpes simplex virus type 1 (HSV-1), an immune response is initiated resulting in significant infiltration of CD8
+
T cells. Previous investigators have observed a lack of apoptosis in HSV-1 trigeminal ganglia even in the presence of cytotoxic immune cells. To determine the role of the latency-associated transcript (LAT) in inhibiting apoptosis, we examined mice during acute and latent infection with HSV-1 (strain 17 or a LAT-negative deletion mutant strain 17 N/H) by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and fluorescence-activated cell sorting (FACS). FACS analysis revealed CD8
+
T cells in the trigeminal ganglia by day 7, with more being present in 17- than 17 N/H-infected trigeminal ganglia (6.22% versus 3.5%) and a decrease in number through day 30 (2.7% to 1.2%). To detect apoptotic CD8
+
T cells, sections were assayed by TUNEL and stained for CD8
+
T cells. By day 7, ∼10% of CD8
+
T cells in both 17- and 17 N/H-infected trigeminal ganglia had undergone apoptosis. By day 30, 58% and 74% of all T cells had undergone apoptosis in 17- and 17 N/H-infected trigeminal ganglia, respectively. Furthermore, no HSV strain 17-infected trigeminal ganglion neurons were apoptotic, but 0.087% of 17ΔSty and 0.98% of 17 N/H-infected neurons were apoptotic. We conclude that the antiapoptotic effect of LAT appears to require the LAT promoter, with most of the antiapoptotic effect mapping within the StyI (+447) to the HpaI (+1667) region and a minor contribution from the upstream StyI (+76) to StyI (+447) region.
Low Human Immunodeficiency Virus Envelope Diversity Correlates with Low In Vitro Replication Capacity and Predicts Spontaneous Control of Plasma Viremia after Treatment Interruptions
Authors: Joos Beda , Trkola Alexandra , Fischer Marek , Kuster Herbert , Rusert Peter , Leemann Christine , Böni Jürg , Oxenius Annette , Price David A. , Phillips Rodney E. , Wong Joseph K. , Hirschel Bernard , Weber Rainer , Günthard Huldrych F. 
Published: July 2005

ABSTRACTGenetic diversity of viral isolates in human immunodeficiency virus (HIV)-infected individuals varies substantially. However, it remains unclear whether HIV-related disease progresses more rapidly in patients harboring virus swarms with low or high diversity and, in the same context, whether high or low diversity is required to induce potent humoral and cellular immune responses. To explore whether viral diversity predicts virologic control, we studied HIV-infected patients who received antiretroviral therapy (ART) for years before undergoing structured treatment interruptions (STI). Viral diversity before initiation of ART and the ability of the patients to contain viremia after STI and final cessation of treatment was evaluated. Seven out of 21 patients contained plasma viremia at low levels after the final treatment cessation. Clonal sequences encompassing the envelope C2V3C3 domain derived from plasma prior to treatment, exhibited significantly lower diversity in these patients compared to those derived from patients with poor control of viremia. Viral diversity pre-ART correlated with the viral replication capacity of rebounding virus isolates during STI. Neutralizing antibody activity against autologous virus was significantly higher in patients who controlled viremia and was associated with lower pretreatment diversity. No such association was found with binding antibodies directed to gp120. In summary, lower pretreatment viral diversity was associated with spontaneous control of viremia, reduced viral replication capacity and higher neutralizing antibody titers, suggesting a link between viral diversity, replication capacity, and neutralizing antibody activity.
Heterologous Late-Domain Sequences Have Various Abilities To Promote Budding of Human Immunodeficiency Virus Type 1
Authors: Ott David E. , Coren Lori V. , Gagliardi Tracy D. , Nagashima Kunio 
Published: July 2005

ABSTRACT

Retroviral late (L) domains present within Gag act in conjunction with cellular proteins to efficiently release virions from the surface of the cell. Three different critical core sequences have been identified as required elements for L-domain function: PPPY, PTAP (also PSAP), and YPDL, with different retroviruses utilizing one or two of these core sequences. The human immunodeficiency virus type 1 (HIV-1) L domain is centered around a PTAP sequence in the p6 region of Gag. To assess the ability of heterologous L-domain sequences to be functionally interchanged for those in full-length HIV-1, we produced a series of constructs that replaced PTAP-containing p6
Gag
sequences with those of PPPY- or YPDL-based L domains. While previous studies had found that L domains are interchangeable in other retroviruses, most of the sequences introduced into p6
Gag
failed to substitute for PTAP-mediated L-domain function. One exception was the 11-amino-acid p2b sequence of Rous sarcoma virus (RSV) Gag, which could fully restore HIV-1 budding, while a PPPPY sequence exchange alone did not. This suggests that the RSV L domain consists of more than simply its core L-domain sequence. The HIV-p2b chimera was as infectious as the wild type, produced normal virions, and was sensitive to proteasome inhibitors. These results show that L-domain sequences are not necessarily interchangeable. Thus, HIV-1 Gag might have a more stringent requirement for L-domain function than the other retroviruses previously studied.
Structural and Functional Analysis of the
cis
-Acting Elements Required for Plus-Strand RNA Synthesis of
Bamboo Mosaic Virus
Authors: Lin Jen-Wen , Chiu Hsiao-Ning , Chen I-Hsuan , Chen Tzu-Chi , Hsu Yau-Heiu , Tsai Ching-Hsiu 
Published: July 2005

ABSTRACT

Bamboo mosaic virus
(BaMV) has a single-stranded positive-sense RNA genome. The secondary structure of the 3′-terminal sequence of the minus-strand RNA has been predicted by MFOLD and confirmed by enzymatic structural probing to consist of a large, stable stem-loop and a small, unstable stem-loop. To identify the promoter for plus-strand RNA synthesis in this region, transcripts of 39, 77, and 173 nucleotides (Ba-39, Ba-77, and Ba-173, respectively) derived from the 3′ terminus of the minus-strand RNA were examined by an in vitro RNA-dependent RNA polymerase assay for the ability to direct RNA synthesis. Ba-77 and Ba-39 appeared to direct the RNA synthesis efficiently, while Ba-173 failed. Ba-77/Δ5, with a deletion of the 3′-terminal UUUUC sequence in Ba-77, directed the RNA synthesis only to 7% that of Ba-77. However, Ba-77/Δ16 and Ba-77/Δ31, with longer deletions but preserving the terminal UUUUC sequence of Ba-77, restored the template activity to about 60% that of the wild type. Moreover, mutations that changed the sequence in the stem of the large stem-loop interfered with the efficiency of RNA synthesis and RNA accumulation in vivo. The mutant with an internal deletion in the region between the terminal UUUUC sequence and the large stem-loop reduced the viral RNA accumulation in protoplasts, but mutants with insertions did not. Taken together, these results suggest that three
cis
-acting elements in the 3′ end of the minus-strand RNA, namely, the terminal UUUUC sequence, the sequence in the large stem-loop, and the distance between these two regions, are involved in modulating the efficiency of BaMV plus-strand viral RNA synthesis.
The V1, V2, and V3 Regions of the Human Immunodeficiency Virus Type 1 Envelope Differentially Affect the Viral Phenotype in an Isolate-Dependent Manner
Authors: Saunders Cheryl J. , McCaffrey Ruth A. , Zharkikh Irina , Kraft Zane , Malenbaum Susan E. , Burke Brian , Cheng-Mayer Cecilia , Stamatatos Leonidas 
Published: July 2005

ABSTRACTIt is well documented that removal of the V1V2 region or of the V2 loop alone from the envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency virus (SIV) increases the susceptibility of these viruses to neutralization by antibodies. The specific role of the V1 loop in defining the neutralization susceptibility of HIV is, however, not well documented. Our current studies indicate that although the V1V2 region is a global modulator of the HIV-1 neutralization susceptibility, the individual roles the V1 and V2 loops have in defining the neutralization susceptibility profile of HIV-1 differ and in some cases are opposite. While deletion of the V2 loop renders the virus more susceptible to neutralization by antibodies that recognize diverse epitopes, in particular certain ones located in the CD4 binding site and the V3 loop, deletion of the V1 loop renders the virus refractory to neutralization, especially by antibodies that recognize CD4-induced epitopes and certain CD4-site binding antibodies. Our current studies also indicate that the relative involvement of the V2 loop of the HIV-1 envelope during virus-cell entry appears to be envelope background dependent. As a result, although deletion of the V2 loop from the clade B, R5-tropic SF162 HIV-1 virus resulted in a virus that was replication competent, the same modification introduced on the background of two other R5-tropic isolates, SF128A (clade B) or SF170 (clade A), abrogated the ability of these envelopes to mediate virus-cell entry.
Defective Replication in Human Immunodeficiency Virus Type 1 When Non-\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{tRNA}_{3}^{\mathrm{Lys}}\) \end{document}Primers Are Used for Reverse Transcription
Authors: Wei Min , Cen Shan , Niu Meijuan , Guo Fei , Kleiman Lawrence 
Published: July 2005

ABSTRACT

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(tRNA_{3}^{Lys}\) \end{document}

, the primer for reverse transcriptase in human immunodeficiency virus type 1 (HIV-1), anneals to the primer binding site (PBS) in HIV-1 RNA. It has been shown that altering the PBS and U5 regions upstream of the PBS in HIV-1 so as to be complementary to sequences in tRNA
Met
or tRNA
His
will allow these tRNA species to be stably used as primers for reverse transcription. We have examined the replication of these mutant viruses in Sup-T1 cells. When Sup-T1 cells are infected by cocultivation with HIV-1-transfected 293T cells, viruses using tRNA
His
or tRNA
Met
are produced at rates that are approximately 1/10 or 1/100, respectively, of rates for wild-type virions that use

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(tRNA_{3}^{Lys}\) \end{document}

. When Sup-T1 cells are directly infected with equal amounts of these different viruses isolated from the culture supernatant of transfected 293T cells, virions using tRNA
Met
are produced at 1/100 the rate of wild-type viruses, and production of virions using tRNA
His
is not detected. Both wild-type and mutant virions selectively package tRNA
Lys
only, and examination of the ability of total viral RNA to prime reverse transcription in vitro indicates a >80% reduction in the annealing of tRNA
His
or tRNA
Met
to the mutant viral RNAs. PCR analysis of which of the three primer tRNAs is used indicates that only

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(tRNA_{3}^{Lys}\) \end{document}

is detected as primer in wild-type virions and only tRNA
His
is detected as primer in virions containing a PBS complementary to tRNA
His
, while the mutant viruses containing a PBS complementary to tRNA
Met
use both tRNA
Met
and

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(tRNA_{1,2}^{Lys}\) \end{document}

as primer tRNAs.
Constituents of SH1, a Novel Lipid-Containing Virus Infecting the Halophilic Euryarchaeon
Haloarcula hispanica
Authors: Bamford Dennis H. , Ravantti Janne J. , Rönnholm Gunilla , Laurinavičius Simonas , Kukkaro Petra , Dyall-Smith Mike , Somerharju Pentti , Kalkkinen Nisse , Bamford Jaana K. H. 
Published: July 2005

ABSTRACT

Recent studies have indicated that a number of bacterial and eukaryotic viruses that share a common architectural principle are related, leading to the proposal of an early common ancestor. A prediction of this model would be the discovery of similar viruses that infect archaeal hosts. Our main interest lies in icosahedral double-stranded DNA (dsDNA) viruses with an internal membrane, and we now extend our studies to include viruses infecting archaeal hosts. While the number of sequenced archaeal viruses is increasing, very little sequence similarity has been detected between bacterial and eukaryotic viruses. In this investigation we rigorously show that SH1, an icosahedral dsDNA virus infecting
Haloarcula hispanica
, possesses lipid structural components that are selectively acquired from the host pool. We also determined the sequence of the 31-kb SH1 genome and positively identified genes for 11 structural proteins, with putative identification of three additional proteins. The SH1 genome is unique and, except for a few open reading frames, shows no detectable similarity to other published sequences, but the overall structure of the SH1 virion and its linear genome with inverted terminal repeats is reminiscent of lipid-containing dsDNA bacteriophages like PRD1.
Genetic Variability and Molecular Evolution of the Human Respiratory Syncytial Virus Subgroup B Attachment G Protein
Authors: Zlateva Kalina T. , Lemey Philippe , Moës Elien , Vandamme Anne-Mieke , Van Ranst Marc 
Published: July 2005

ABSTRACT

Human respiratory syncytial virus (HRSV) is the most important cause of acute respiratory disease in infants. Two major subgroups (A and B) have been identified based on antigenic differences in the attachment G protein. Antigenic variation between and within the subgroups may contribute to reinfections with these viruses by evading the host immune responses. To investigate the circulation patterns and mechanisms by which HRSV-B viruses evolve, we analyzed the G protein genetic variability of subgroup B sequences isolated over a 45-year period, including 196 Belgian strains obtained over 22 epidemic seasons (1982 to 2004). Our study revealed that the HRSV-B evolutionary rate (1.95 × 10
−3
nucleotide substitutions/site/year) is similar to that previously estimated for HRSV-A (1.83 × 10
−3
nucleotide substitutions/site/year). However, natural HRSV-B isolates appear to accommodate more drastic changes in their attachment G proteins. The most recent common ancestor of the currently circulating subgroup B strains was estimated to date back to around the year 1949. The divergence between the two major subgroups was calculated to have occurred approximately 350 years ago. Furthermore, we have identified 12 positively selected sites in the G protein ectodomain, suggesting that immune-driven selective pressure operates in certain codon positions. HRSV-A and -B strains have similar phylodynamic patterns: both subgroups are characterized by global spatiotemporal strain dynamics, where the high infectiousness of HRSV permits the rapid geographic spread of novel strain variants.
Infectious Pancreatic Necrosis Virus VP5 Is Dispensable for Virulence and Persistence
Authors: Santi Nina , Song Haichen , Vakharia Vikram N. , Evensen Øystein 
Published: July 2005

ABSTRACT
Infectious pancreatic necrosis virus (IPNV) is the causative agent of infectious pancreatic necrosis (IPN) disease in salmonid fish. Recent studies have revealed variation in virulence between isolates of the Sp serotype, associated with certain residues of the structural protein VP2. The isolates are also highly heterogenic in the coding region of the nonstructural VP5 protein. To study the involvement of this protein in the pathogenesis of disease, we generated three recombinant VP5 mutant viruses using reverse genetics. The “wild-type” recombinant NVI15 (rNVI15) virus is virulent, having a premature stop codon at nucleotide position 427, putatively encoding a truncated 12-kDa VP5 protein, whereas rNVI15-15K virus encodes a 15-kDa protein. Recombinant rNVI15-ΔVP5 virus contains a mutation in the initiation codon of the VP5 gene that ablates the expression of VP5. Atlantic salmon postsmolts were challenged to study the virulence characteristics of the recovered viruses in vivo. The role of VP5 in persistent infection was investigated by challenging Atlantic salmon fry with the recovered viruses, as well as with the low-virulence field strain Sp103 and a naturally occurring VP5-deficient mutant of Sp103. The results show that VP5 is not required for viral replication in vivo, and its absence does not alter the virulence characteristics of the virus or the establishment of persistent IPNV infection.
The Marine Algal Virus PpV01 Has an Icosahedral Capsid with T=219 Quasisymmetry
Authors: Yan Xiaodong , Chipman Paul R. , Castberg Tonje , Bratbak Gunnar , Baker Timothy S. 
Published: July 2005

ABSTRACT

Phaeocystis pouchetii
virus (PpV01) infects and lyses the haptophyte
Phaeocystis pouchetii
(Hariot) Lagerheim and was first isolated from Norwegian coastal waters. We have used electron cryomicroscopy and three-dimensional image reconstruction methods to examine the native morphology of PpV01 at a resolution of 3 nm. The icosahedral capsid of PpV01 has a maximum diameter of 220 nm and is composed of 2,192 capsomers arranged with T=219 quasisymmetry. One specific capsomer in each asymmetric unit contains a fiber-like protrusion. Density attributed to the presence of a lipid membrane appears just below (inside) the capsid. PpV01 is the largest icosahedral virus whose capsid structure has been determined in three dimensions from images of vitrified samples. Striking similarities in the structures of PpV01 and a number of other large double-stranded DNA viruses are consistent with a growing body of evidence that they share a common evolutionary origin.
A Downstream Polyadenylation Element in Human Papillomavirus Type 16 L2 Encodes Multiple GGG Motifs and Interacts with hnRNP H
Authors: Öberg Daniel , Fay Joanna , Lambkin Helen , Schwartz Stefan 
Published: July 2005

ABSTRACT
Production of human papillomavirus type 16 (HPV-16) virus particles is totally dependent on the differentiation-dependent induction of viral L1 and L2 late gene expression. The early polyadenylation signal in HPV-16 plays a major role in the switch from the early to the late, productive stage of the viral life cycle. Here, we show that the L2 coding region of HPV-16 contains RNA elements that are necessary for polyadenylation at the early polyadenylation signal. Consecutive mutations in six GGG motifs located 174 nucleotides downstream of the polyadenylation signal resulted in a gradual decrease in polyadenylation at the early polyadenylation signal. This caused read-through into the late region, followed by production of the late mRNAs encoding L1 and L2. Binding of hnRNP H to the various triple-G mutants correlated with functional activity of the HPV-16 early polyadenylation signal. In addition, the polyadenylation factor CStF-64 was also found to interact specifically with the region in L2 located 174 nucleotides downstream of the early polyadenylation signal. Staining of cervix epithelium with anti-hnRNP H-specific antiserum revealed high expression levels of hnRNP H in the lower layers of cervical epithelium and a loss of hnRNP H production in the superficial layers, supporting a model in which a differentiation-dependent down regulation of hnRNP H causes a decrease in HPV-16 early polyadenylation and an induction of late gene expression.
A Genetically Engineered Attenuated Coxsackievirus B3 Strain Protects Mice against Lethal Infection
Authors: Dan M. , Chantler J. K. 
Published: July 2005

ABSTRACT
Coxsackievirus B3 (CVB3) is a common human pathogen that is endemic throughout the world. There is currently no vaccine available, although the virus is known to be highly lethal to newborns and has been associated with heart disease and pancreatitis in older children and adults. Previously, we showed that the virulence of CVB3 is reduced by a lysine-to-arginine substitution in the capsid protein VP2 (K2168R) or a glutamic acid-to-glycine substitution in VP3 (E3060G). In this report, we show that the double mutant virus CVB3(KR/EG) displays additional attenuation, particularly for the pancreas, in A/J mice. In addition, two other attenuating mutations have been identified in the capsid protein VP1. When either the aspartic acid residue D1155 was replaced with glutamic acid or the proline residue P1126 was replaced with methionine, the resulting mutant also possessed an attenuated phenotype. Moreover, when either of these mutations was incorporated into CVB3(KR/EG), the resulting triple mutant viruses, CVB3(KR/EG/DE) and CVB3(KR/EG/PM), were completely noncardiovirulent and caused only small foci of damage to the pancreas, even at a high dose. Both triple mutants were found to be immunogenic, and a single injection of young A/J mice with either was found to protect them from a subsequent lethal challenge with wild-type CVB3. These findings indicate that the triple mutants could be exploited for the development of a live attenuated vaccine against CVB3.
Cloning and Identification of a MicroRNA Cluster within the Latency-Associated Region of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Samols Mark A. , Hu Jianhong , Skalsky Rebecca L. , Renne Rolf 
Published: July 2005

ABSTRACT
MicroRNAs (miRNAs) are small, noncoding regulatory RNA molecules that bind to 3′ untranslated regions (UTRs) of mRNAs to either prevent their translation or induce their degradation. Previously identified in a variety of organisms ranging from plants to mammals, miRNAs are also now known to be produced by viruses. The human gammaherpesvirus Epstein-Barr virus has been shown to encode miRNAs, which potentially regulate both viral and cellular genes. To determine whether Kaposi's sarcoma-associated herpesvirus (KSHV) encodes miRNAs, we cloned small RNAs from KSHV-positive primary effusion lymphoma-derived cells and endothelial cells. Sequence analysis revealed 11 isolated RNAs of 19 to 23 bases in length that perfectly align with KSHV. Surprisingly, all candidate miRNAs mapped to a single genomic locale within the latency-associated region of KSHV. These data suggest that viral and host cellular gene expression may be regulated by miRNAs during both latent and lytic KSHV replication.
RNA-Dependent Protein Kinase Is Required for Alpha-1 Interferon Transgene-Induced Resistance to Genital Herpes Simplex Virus Type 2
Authors: Carr Daniel J. J. , Tomanek Lisa , Silverman Robert H. , Campbell Iain L. , Williams Bryan R. G. 
Published: July 2005

ABSTRACTWe investigated the mechanism of resistance to genital herpes simplex virus type 2 (HSV-2) infection in mice transfected with the murine alpha-1 interferon (IFN-α1) transgene. In situ transfection of mice with the IFN-α1 transgene resulted in an elevation in an IFN-responsive gene, RNA-dependent protein kinase (PKR), but not 2′,5′-oligoadenylate synthetases (OAS), in vaginal tissue. Coupled with the finding that mice lacking a functional PKR pathway were no longer resistant to genital HSV-2 infection following transfection with the IFN-α1 transgene in comparison to wild-type mice or mice lacking a functional OAS pathway, these results suggest that PKR is the dominant antiviral pathway activated by the IFN-α1 transgene.