bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Down-Regulation of the NKG2D Ligand H60 by Mouse Cytomegalovirus m155 Glycoprotein
Authors: Hasan Milena , Krmpotic Astrid , Ruzsics Zsolt , Bubic Ivan , Lenac Tihana , Halenius Anne , Loewendorf Andrea , Messerle Martin , Hengel Hartmut , Jonjic Stipan , Koszinowski Ulrich H. 
Published: February 2005

ABSTRACTBoth human and mouse cytomegaloviruses (CMVs) encode proteins that inhibit the activation of NK cells by down-regulating cellular ligands for the activating NK cell receptor NKG2D. Up to now, three ligands for the NKG2D receptor, named RAE-1, H60, and MULT-1, have been identified in mice. The resistance of mouse strains to murine CMV (MCMV) infection is determined by their ability to generate an effective NK cell response. The MCMV genem152, a member of them145gene family, down-regulates the expression of RAE-1 in order to avoid NK cell control in vivo. Here we report that them155gene, another member of them145gene family, encodes a protein that interferes with the expression of H60 on the surfaces of infected cells. Deletion of them155gene leads to an only partial restoration of H60 expression on the cell surface, suggesting the involvement of another, so far unknown, viral inhibitor. In spite of this, anm155deletion mutant virus shows NK cell-dependent attenuation in vivo. The acquisition of endo-β-N-acetylglucosaminidase H resistance and the preserved half-life of H60 in MCMV-infected cells indicate that the m155-mediated effect must take place in a compartment after H60 exits from the ERGIC-cis-Golgi compartment.
Human Endogenous Retrovirus HERV-K14 Families: Status, Variants, Evolution, and Mobilization of Other Cellular Sequences
Authors: Flockerzi Aline , Burkhardt Stefan , Schempp Werner , Meese Eckart , Mayer Jens 
Published: February 2005

ABSTRACTThe human genome harbors many distinct families of human endogenous retroviruses (HERVs) that stem from exogenous retroviruses that infected the germ line millions of years ago. Many HERV families remain to be investigated. We report in the present study the detailed characterization of the HERV-K14I and HERV-K14CI families as they are represented in the human genome. Most of the 68 HERV-K14I and 23 HERV-K14CI proviruses are severely mutated, frequently displaying uniform deletions of retroviral genes and long terminal repeats (LTRs). Both HERV families entered the germ line ∼39 million years ago, as evidenced by homologous sequences in hominoids and Old World primates and calculation of evolutionary ages based on a molecular clock. Proviruses of both families were formed during a brief period. A majority of HERV-K14CI proviruses on the Y chromosome mimic a higher evolutionary age, showing that LTR-LTR divergence data can indicate false ages. Fully translatable consensus sequences encoding major retroviral proteins were generated. Most HERV-K14I loci lack anenvgene and are structurally reminiscent of LTR retrotransposons. A minority of HERV-K14I variants display anenvgene. HERV-K14I proviruses are associated with three distinct LTR families, while HERV-K14CI is associated with a single LTR family. Hybrid proviruses consisting of HERV-K14I and HERV-W sequences that appear to have produced provirus progeny in the genome were detected. Several HERV-K14I proviruses harbor TRPC6 mRNA portions, exemplifying mobilization of cellular transcripts by HERVs. Our analysis contributes essential information on two more HERV families and on the biology of HERV sequences in general.
Growth of Hepatitis A Virus in a Mouse Liver Cell Line
Authors: Feigelstock Dino A. , Thompson Peter , Kaplan Gerardo G. 
Published: February 2005

ABSTRACT
Hepatitis A virus (HAV) has been adapted to grow efficiently in primate and some nonprimate cell lines but not in cells of murine origin. To understand the inability of the virus to grow in mouse cells, we studied the replication of HAV in immortalized and nontransformed MMH-D3 mouse liver cells, which require growth factors and collagen to maintain their phenotype. HAV grew in MMH-D3 cells transfected with virion RNA but not in those infected with viral particles, indicating a cell entry block for HAV. However, MMH-D3 cells cultured under suboptimal conditions in the absence of growth factors acquired susceptibility to HAV infection. Serial passages of the virus in MMH-D3 cells under suboptimal growth conditions resulted in the selection of HAV variants that grew efficiently in MMH-D3 cells cultured under both optimal and suboptimal conditions. Nucleotide sequence analysis of the MMH-D3 cell-adapted HAV revealed that N1237D and D2132G substitutions were present in the capsid regions of six viral clones. These two mutations are most likely located on the surface of the virion and may play a role in the entry of HAV into the mouse liver cells. Our results demonstrate that mouse hepatocyte-like cells code for all factors required for the efficient growth of HAV in cell culture.
Lactoferrin Prevents Dendritic Cell-Mediated Human Immunodeficiency Virus Type 1 Transmission by Blocking the DC-SIGN—gp120 Interaction
Authors: Groot Fedde , Geijtenbeek Teunis B. H. , Sanders Rogier W. , Baldwin Christopher E. , Sanchez-Hernandez Marta , Floris René , van Kooyk Yvette , de Jong Esther C. , Berkhout Ben 
Published: February 2005

ABSTRACT

One of the cell types first encountered by human immunodeficiency virus type 1 (HIV-1) following sexual transmission are dendritic cells (DC). DC capture HIV-1 through C-type lectin receptors, of which the best studied example is DC-SIGN, which mediates HIV-1 internalization. DC can keep the virus infectious for several days and are able to transmit HIV-1 to CD4
+
T cells. We tested proteins from milk and serum for their ability to block DC-mediated HIV-1 transmission, of which bovine lactoferrin (bLF) is the most potent inhibitor. bLF binds strongly to DC-SIGN, thus preventing virus capture and subsequent transmission. Interestingly, bLF is a much more efficient inhibitor of transmission than human lactoferrin. Since bLF is nontoxic and easy to purify in large quantities, it is an interesting candidate microbicide against HIV-1. Another advantage of bLF is its ability to block HIV-1 replication in T cells. DC-mediated capture of a bLF-resistant HIV-1 variant that was selected during long-term culturing in T cells could still be blocked by bLF. This underscores the usefulness of bLF as a microbicide drug to prevent HIV-1 transmission.
Identification and Genomic Characterization of a New Virus (
Tymoviridae
Family) Associated with Citrus Sudden Death Disease
Authors: Maccheroni Walter , Alegria Marcos C. , Greggio Christian C. , Piazza João Paulo , Kamla Rachel F. , Zacharias Paula R. A. , Bar-Joseph Moshe , Kitajima Elliot W. , Assumpção Laura C. , Camarotte Giovana , Cardozo Jussara , Casagrande Elaine C. , Ferrari Fernanda , Franco Sulamita F. , Giachetto Poliana F. , Girasol Alessandra , Jordão Hamilton , Silva Vitor H. A. , Souza Leonardo C. A. , Aguilar-Vildoso Carlos I. , Zanca Almir S. , Arruda Paulo , Kitajima João Paulo , Reinach Fernando C. , Ferro Jesus A. , da Silva Ana C. R. 
Published: February 2005

ABSTRACT

Citrus sudden death (CSD) is a new disease that has killed approximately 1 million orange trees in Brazil. Here we report the identification of a new virus associated with the disease. RNAs isolated from CSD-affected and nonaffected trees were used to construct cDNA libraries. A set of viral sequences present exclusively in libraries of CSD-affected trees was used to obtain the complete genome sequence of the new virus. Phylogenetic analysis revealed that this virus is a new member of the genus
Marafivirus
. Antibodies raised against the putative viral coat proteins allowed detection of viral antigens of expected sizes in affected plants. Electron microscopy of purified virus confirmed the presence of typical isometric
Marafivirus
particles. The screening of 773 affected and nonaffected citrus trees for the presence of the virus showed a 99.7% correlation between disease symptoms and the presence of the virus. We also detected the virus in aphids feeding on affected trees. These results suggest that this virus is likely to be the causative agent of CSD. The virus was named
Citrus sudden death-associated virus
.
Processing and Presentation of Exogenous HLA Class I Peptides by Dendritic Cells from Human Immunodeficiency Virus Type 1-Infected Persons
Authors: Huang Xiao-Li , Fan Zheng , Colleton Bonnie A. , Buchli Rico , Li Hongyi , Hildebrand William H. , Rinaldo Charles R. 
Published: February 2005

ABSTRACTDendritic cells (DCs) loaded with viral peptides are a potential form of immunotherapy of human immunodeficiency virus type 1 (HIV-1) infection. We show that DCs derived from blood monocytes of subjects with chronic HIV-1 infection on combination antiretroviral drug therapy have increases in expression of HLA, T-cell coreceptor, and T-cell activation molecules in response to the DC maturation factor CD40L comparable to those from uninfected persons. Mature DCs (mDCs) loaded with HLA A*0201-restricted viral peptides of the optimal length (9-mer) were more efficient at activating antiviral CD8+T cells than were immature DCs or peptide alone. Optimal presentation of these exogenous peptides required uptake and vesicular trafficking and was comparable in DCs derived from HIV-1-infected and uninfected persons. Furthermore, DCs from HIV-1-infected and uninfected persons had similar capacities to process viral peptides with C-terminal and N-terminal extensions through their proteasomal and cytosolic pathways, respectively. We conclude that DCs derived from HIV-1-infected persons have similar abilities to process exogenous peptides for presentation to CD8+T cells as those from uninfected persons. This conclusion supports the use of DCs loaded with synthetic peptides in immunotherapy of HIV-1 infection.
Anatomical and Cellular Requirements for the Activation and Migration of Virus-Specific CD8+T Cells to the Brain during Theiler's Virus Infection
Authors: Mendez-Fernandez Yanice V. , Hansen Michael J. , Rodriguez Moses , Pease Larry R. 
Published: February 2005

ABSTRACTTheiler's murine encephalomyelitis virus (TMEV) infection of the brain induces a virus-specific CD8+T-cell response in genetically resistant mice. The peak of the immune response to the virus occurs 7 days after infection, with an immunodominant CD8+T-cell response against a VP2-derived capsid peptide in the context of the Dbmolecule. The process of activation of antigen-specific T cells that migrate to the brain in the TMEV model has not been defined. The site of antigenic challenge in the TMEV model is directly into the brain parenchyma, a site that is considered immune privileged. We investigated the hypothesis that antiviral CD8+T-cell responses are initiated in situ upon intracranial inoculation with TMEV. To determine whether a brain parenchymal antigen-presenting cell is responsible for the activation of virus-specific CD8+T cells, we evaluated the CD8+T-cell response to the VP2 peptide in bone marrow chimeras and mutant mice lacking peripheral lymphoid organs. The generation of the anti-TMEV CD8+T-cell response in the brain requires priming by a bone marrow-derived antigen-presenting cell and the presence of peripheral lymphoid organs. Although our results show that activation of TMEV-specific CD8+T cells occurs in the peripheral lymphoid compartment, they do not exclude the possibility that the immune response to TMEV is initiated by a brain-resident, bone marrow-derived, antigen-presenting cell.
Quasispecies Heterogeneity within the E1/E2 Region as a Pretreatment Variable during Pegylated Interferon Therapy of Chronic Hepatitis C Virus Infection
Authors: Chambers Thomas J. , Fan Xiaofeng , Droll Deborah A. , Hembrador Edgardo , Slater Tiffany , Nickells Michael W. , Dustin Lynn B. , DiBisceglie Adrian M. 
Published: February 2005

ABSTRACT
A series of 29 patients undergoing treatment for chronic hepatitis C virus (HCV) genotype 1 infection with pegylated alpha-2a interferon plus ribavirin were studied for patterns of response to antiviral therapy and viral quasispecies evolution. All patients were treatment naive and had chronic inflammation and fibrosis on biopsy. As part of an analysis of pretreatment variables that might affect the outcome of treatment, genetic heterogeneity within the viral E1-E2 glycoprotein region (nucleotides 851 to 2280) was assessed by sequencing 10 to 15 quasispecies clones per patient from serum-derived PCR products. Genetic parameters were examined with respect to response to therapy based on serum viral RNA loads at 12 weeks (early viral response) and at 24 weeks posttreatment (sustained viral response). Nucleotide and amino acid quasispecies complexities of the hypervariable region 1 (HVR-1) were less in the responder group in comparison to the nonresponder group at 12 weeks, and genetic diversity was also less both within and outside of the HVR-1, with the difference being most pronounced for the non-HVR-1 region of E2. However, these genetic parameters did not distinguish responders from nonresponders for sustained viral responses. Follow-up studies of genetic heterogeneity based on the HVR-1 in selected responders and nonresponders while on therapy revealed greater evolutionary drift in the responder subgroup. The pretreatment population sequences for the NS5A interferon sensitivity determinant region were also analyzed for all patients, but no correlations were found between treatment response and any distinct genetic markers. These findings support previous studies indicating a high level of genetic heterogeneity among chronically infected HCV patients. One interpretation of these data is that early viral responses are governed to some extent by viral factors, whereas sustained responses may be more influenced by host factors, in addition to effects of viral complexity and diversity.
Recombinant Mouse Hepatitis Virus Strain A59 from Cloned, Full-Length cDNA Replicates to High Titers In Vitro and Is Fully Pathogenic In Vivo
Authors: Coley Scott E. , Lavi Ehud , Sawicki Stanley G. , Fu Li , Schelle Barbara , Karl Nadja , Siddell Stuart G. , Thiel Volker 
Published: February 2005

ABSTRACT

Mouse hepatitis virus (MHV) is the prototype of group II coronaviruses and one of the most extensively studied coronaviruses. Here, we describe a reverse genetic system for MHV (strain A59) based upon the cloning of a full-length genomic cDNA in vaccinia virus. We show that the recombinant virus generated from cloned cDNA replicates to the same titers as the parental virus in cell culture (∼10
9
PFU/ml), has the same plaque morphology, and produces the same amounts and proportions of genomic and subgenomic mRNAs in virus-infected cells. In a mouse model of neurological infection, the recombinant and parental viruses are equally virulent, they replicate to the same titers in brain and liver, and they induce similar patterns of acute hepatitis, acute meningoencephalitis, and chronic demyelination. We also describe improvements in the use of the coronavirus reverse genetic system based on vaccinia virus cloning vectors. These modifications facilitate (i) the mutagenesis of cloned cDNA by using vaccinia virus-mediated homologous recombination and (ii) the rescue of recombinant coronaviruses by using a stable nucleocapsid protein-expressing cell line for the electroporation of infectious full-length genomes. Thus, our system represents a versatile and universal tool to study all aspects of MHV molecular biology and pathogenesis. We expect this system to provide valuable insights into the replication of group II coronaviruses that may lead to the development of novel strategies against coronavirus infections, including the related severe acute respiratory syndrome coronavirus.
The Latency-Associated Nuclear Antigen of Rhesus Monkey Rhadinovirus Inhibits Viral Replication through Repression of Orf50/Rta Transcriptional Activation
Authors: DeWire Scott M. , Damania Blossom 
Published: February 2005

ABSTRACT
Rhesus monkey rhadinovirus (RRV) is a gamma-2-herpesvirus that is closely related to Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8. We have previously reported that the transcript for RRV latency-associated nuclear antigen (R-LANA) is expressed during lytic replication in rhesus fibroblasts. In this article, we report the development of a latent culture system for RRV and show that mRNA specific for R-LANA is expressed during latency as well. We have characterized the R-LANA protein and demonstrate that it exhibits a nuclear speckled localization and possesses the ability to homodimerize. When expressed in rhesus fibroblasts, R-LANA can inhibit RRV lytic replication in vitro. We have investigated the mechanism behind this inhibition and find that, while R-LANA itself has very little effect on lytic promoters, it can dramatically decrease the transactivation function of RRV Orf50 (Rta), which is the major viral transcription factor. We further show that the mechanism for this repression involves the recruitment of histone deacetylase complexes (HDACs), because R-LANA's ability to repress Orf50 transactivation is completely reversed by the addition of the HDAC inhibitor trichostatin A (TSA). We also report that TSA alone can significantly reactivate RRV from latently infected cells. We propose that the repressive effects of R-LANA on RRV Orf50 transactivation serve to downregulate the transcription of early genes at late times during the lytic cycle and also help to maintain viral latency by preventing viral reactivation.
Species-Specific Variation in the B30.2(SPRY) Domain of TRIM5α Determines the Potency of Human Immunodeficiency Virus Restriction
Authors: Stremlau Matthew , Perron Michel , Welikala Sohanya , Sodroski Joseph 
Published: February 2005

ABSTRACT

Retroviruses encounter dominant postentry restrictions in cells of particular species. Human immunodeficiency virus type 1 (HIV-1) is blocked in the cells of Old World monkeys by TRIM5α, a tripartite motif (TRIM) protein composed of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. Rhesus monkey TRIM5α (TRIM5α
rh
) more potently blocks HIV-1 infection than human TRIM5α (TRIM5α
hu
). Here, by studying chimeric TRIM5α proteins, we demonstrate that the major determinant of anti-HIV-1 potency is the B30.2(SPRY) domain. Analysis of species-specific variation in TRIM5α has identified three variable regions (v1, v2, and v3) within the B30.2 domain. The TRIM5α proteins of Old World primates exhibit expansion, duplication, and residue variation specifically in the v1 region. Replacement of three amino acids in the N terminus of the TRIM5α
hu
B30.2 v1 region with the corresponding TRIM5α
rh
residues resulted in a TRIM5α molecule that restricted HIV-1 nearly as efficiently as wild-type TRIM5α
rh
. Surprisingly, a single-amino-acid change in this region of TRIM5α
hu
allowed potent restriction of simian immunodeficiency virus, a phenotype not observed for either wild-type TRIM5α
hu
or TRIM5α
rh
. Some of the chimeric TRIM5α proteins that are >98% identical to the human protein yet mediate a strong restriction of HIV-1 infection may have therapeutic utility. These observations implicate the v1 variable region of the B30.2(SPRY) domain in TRIM5α
rh
antiviral potency.
Interferon Regulatory Factor 3-Independent Double-Stranded RNA-Induced Inhibition of Hepatitis C Virus Replicons in Human Embryonic Kidney 293 Cells
Authors: Ali Samir , Kukolj George 
Published: February 2005

ABSTRACT
The treatment of human embryonic kidney 293 cells harboring a hepatitis C virus (HCV) subgenomic replicon with the double-stranded RNA (dsRNA) mimic poly(I · C) inhibits HCV RNA replication through an undefined mechanism. Interferon regulatory factor 3 (IRF 3) has been widely postulated to mediate various antiviral responses, and its role in mediating the response to dsRNA in 293 cells was examined. Treating the cells with dsRNA did not induce IRF-3 activation, as measured by nuclear localization or the induction of reporter genes. Moreover, the expression of a dominant negative form of IRF-3 did not affect either colony formation upon transfection of subgenomic replicon RNA or the inhibition of the HCV replicon by dsRNA. Our results suggest that the inhibition of HCV RNA replication by poly(I · C) in 293 cells is independent of IRF-3 activation.
Alternative tRNA Priming of Human Immunodeficiency Virus Type 1 Reverse Transcription Explains Sequence Variation in the Primer-Binding Site That Has Been Attributed to APOBEC3G Activity
Authors: Das Atze T. , Vink Monique , Berkhout Ben 
Published: February 2005

ABSTRACT

It is generally assumed that human immunodeficiency virus type 1 (HIV-1) uses exclusively the cellular

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molecule as a primer for reverse transcription. We demonstrate that HIV-1 uses not only

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but also an alternative tRNA primer. This tRNA was termed

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, and the near completion of the human genome project has allowed the identification of four

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encoding genes. Priming with

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results in a single nucleotide polymorphism in the viral primer-binding site that is present in multiple natural and laboratory HIV isolates. This sequence variation was recently attributed to APOBEC3G activity. However, our results show that alternative tRNA priming can cause this mutation in the absence of APOBEC3G.
Interleukin 7 Increases Human Immunodeficiency Virus Type 1 LAI-Mediated Fas-Induced T-Cell Death
Authors: Lelièvre Jean-Daniel , Petit Frédéric , Arnoult Damien , Ameisen Jean-Claude , Estaquier Jérôme 
Published: February 2005

ABSTRACTFas-mediated T-cell death is known to occur during human immunodeficiency virus (HIV) infection. In this study, we found that HIV type 1 LAI (HIV-1LAI) primes CD8+T cells from healthy donors for apoptosis, which occurs after Fas ligation. This effect is counteracted by a broad caspase inhibitor (zVAD-fmk). Fas-mediated cell death does not depend on CD8+T-cell infection, because it occurred in the presence of reverse transcriptase inhibitors. However, purified CD8+T cells are sensitive to Fas only in the presence of soluble CD4. Finally, we found that interleukin 7 (IL-7) increases Fas-mediated CD4+and CD8+T-cell death induced by HIV-1LAI. Since high levels of IL-7 are a marker of poor prognosis during HIV infection, our data suggest that enhancement of Fas-mediated T-cell death by HIV-1LAIand IL-7 is one of the mechanisms involved in progression to AIDS.