bluuebunny/crossref_metadata_2025_split huggingface dataset:
Entire Genome of a Strain of Human Immunodeficiency Virus Type 1 with a Deletion of
nef
That Was Recovered 20 Years after Primary Infection: Large Pool of Proviruses with Deletions of
env
Authors: Calugi Graziella , Montella Francesco , Favalli Cartesio , Benedetto Arrigo 
Published: November 2006

ABSTRACT

We report the complete sequence analysis of the provirus harbored in a long-term nonprogressor (patient SG1) 20 years after the first infection with a human immunodeficiency virus type 1 strain lacking
nef
. The sequencing showed large deletions in the
nef-nef
and
nef-
U3 regions. Except for
vpu
, all of the other accessory genes were intact. The
gag
and
pol
genes did not show significant alterations. We found large deletions in
env
, spanning the V1, V2, V3, V4, and V5 regions. We believe that, when down-regulation of the class 1 major histocompatibility complex molecules is inhibited by the lack of
nef
function, the cells containing Env-defective molecules evade cytotoxic T lymphocyte killing and accumulate progressively.
Human Cytomegalovirus (HCMV) Infection of Endothelial Cells Promotes Naïve Monocyte Extravasation and Transfer of Productive Virus To Enhance Hematogenous Dissemination of HCMV
Authors: Bentz Gretchen L. , Jarquin-Pardo Marta , Chan Gary , Smith M. Shane , Sinzger Christian , Yurochko Andrew D. 
Published: November 2006

ABSTRACTHuman cytomegalovirus (HCMV) pathogenesis is dependent on the hematogenous spread of the virus to host tissue. While data suggest that infected monocytes are required for viral dissemination from the blood to the host organs, infected endothelial cells are also thought to contribute to this key step in viral pathogenesis. We show here that HCMV infection of endothelial cells increased the recruitment and transendothelial migration of monocytes. Infection of endothelial cells promoted the increased surface expression of cell adhesion molecules (intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and platelet endothelial cell adhesion molecule 1), which were necessary for the recruitment of naïve monocytes to the apical surface of the endothelium and for the migration of these monocytes through the endothelial cell layer. As a mechanism to account for the increased monocyte migration, we showed that HCMV infection of endothelial cells increased the permeability of the endothelium. The cellular changes contributing to the increased permeability and increased naïve monocyte transendothelial migration include the disruption of actin stress fiber formation and the decreased expression of lateral junction proteins (occludin and vascular endothelial cadherin). Finally, we showed that the migrating monocytes were productively infected with the virus, documenting that the virus was transferred to the migrating monocyte during passage through the lateral junctions. Together, our results provide evidence for an active role of the infected endothelium in HCMV dissemination and pathogenesis.
Inhibition of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{tRNA}_{3}^{\mathrm{Lys}}\) \end{document}-Primed Reverse Transcription by Human APOBEC3G during Human Immunodeficiency Virus Type 1 Replication
Authors: Guo Fei , Cen Shan , Niu Meijuan , Saadatmand Jenan , Kleiman Lawrence 
Published: November 2006

ABSTRACT

Cells are categorized as being permissive or nonpermissive according to their ability to produce infectious human immunodeficiency virus type 1 (HIV-1) lacking the viral protein Vif. Nonpermissive cells express the human cytidine deaminase APOBEC3G (hA3G), and Vif has been shown to bind to APOBEC3G and facilitate its degradation. Vif-negative HIV-1 virions produced in nonpermissive cells incorporate hA3G and have a severely reduced ability to produce viral DNA in newly infected cells. While it has been proposed that the reduction in DNA production is due to hA3G-facilitated deamination of cytidine, followed by DNA degradation, we provide evidence here that a decrease in the synthesis of the DNA by reverse transcriptase may account for a significant part of this reduction. During the infection of cells with Vif-negative HIV-1 produced from 293T cells transiently expressing hA3G, much of the inhibition of early (≥50% reduction) and late (≥95% reduction) viral DNA production, and of viral infectivity (≥95% reduction), can occur independently of DNA deamination. The inhibition of the production of early minus-sense strong stop DNA is also correlated with a similar inability of tRNA
3
Lys
to prime reverse transcription. A similar reduction in tRNA
3
Lys
priming and viral infectivity is also seen in the naturally nonpermissive cell H9, albeit at significantly lower levels of hA3G expression.
Recombination Patterns in Aphthoviruses Mirror Those Found in Other Picornaviruses
Authors: Heath Livio , van der Walt Eric , Varsani Arvind , Martin Darren P. 
Published: November 2006

ABSTRACT

Foot-and-mouth disease virus
(FMDV) is thought to evolve largely through genetic drift driven by the inherently error-prone nature of its RNA polymerase. There is, however, increasing evidence that recombination is an important mechanism in the evolution of these and other related picornoviruses. Here, we use an extensive set of recombination detection methods to identify 86 unique potential recombination events among 125 publicly available FMDV complete genome sequences. The large number of events detected between members of different serotypes suggests that horizontal flow of sequences among the serotypes is relatively common and does not incur severe fitness costs. Interestingly, the distribution of recombination breakpoints was found to be largely nonrandom. Whereas there are clear breakpoint cold spots within the structural genes, two statistically significant hot spots precisely separate these from the nonstructural genes. Very similar breakpoint distributions were found for other picornovirus species in the genera
Enterovirus
and
Teschovirus
. Our results suggest that genome regions encoding the structural proteins of both FMDV and other picornaviruses are functionally interchangeable modules, supporting recent proposals that the structural and nonstructural coding regions of the picornaviruses are evolving largely independently of one another.
The NPro Product of Bovine Viral Diarrhea Virus Inhibits DNA Binding by Interferon Regulatory Factor 3 and Targets It for Proteasomal Degradation
Authors: Hilton Louise , Moganeradj Kartykayan , Zhang Gang , Chen Yun-Hsiang , Randall Richard E. , McCauley John W. , Goodbourn Stephen 
Published: November 2006

ABSTRACT

Bovine viral diarrhea virus
(BVDV) is a pestivirus that can establish a persistent infection in the developing fetus and has the ability to disable the production of type I interferon. In this report, we extend our previous observations that BVDV encodes a protein able to specifically block the activity of interferon regulatory factor 3 (IRF-3), a transcription factor essential for interferon promoter activation, by demonstrating that this is a property of the N-terminal protease fragment (NPro) of the BVDV polyprotein. Although BVDV infections cause relocalization of cellular IRF-3 from the cytoplasm to the nucleus early in infection, NPro blocks IRF-3 from binding to DNA. NPro has the additional property of targeting IRF-3 for polyubiquitination and subsequent destruction by cellular multicatalytic proteasomes. The autoprotease activity of NPro is not required for the inhibition of type I interferon induction or the targeting of IRF-3 for degradation.
Autographa californica
Multiple Nucleopolyhedrovirus Nucleocapsid Assembly Is Interrupted upon Deletion of the
38K
Gene
Authors: Wu Wenbi , Lin Tiehao , Pan Lijing , Yu Mei , Li Zhaofei , Pang Yi , Yang Kai 
Published: November 2006

ABSTRACT

38K
(
ac98
) of
Autographa californica
multiple nucleopolyhedrovirus (Ac
M
NPV) is a highly conserved baculovirus gene whose function is unknown. To determine the role of
38K
in the baculovirus life cycle, a
38K
knockout bacmid containing the Ac
M
NPV genome was generated through homologous recombination in
Escherichia coli
. Furthermore, a
38K
repair bacmid was constructed by transposing the
38K
open reading frame with its native promoter region into the
polyhedrin
locus of the
38K
knockout bacmid. After transfection of these viruses into
Spodoptera frugiperda
cells, the
38K
knockout bacmid led to a defect in production of infectious budded virus, while the
38K
repair bacmid rescued this defect, allowing budded-virus titers to reach wild-type levels. Slot blot analysis indicated that
38K
deletion did not affect the levels of viral DNA replication. Subsequent immunoelectron-microscopic analysis revealed that masses of electron-lucent tubular structures containing the capsid protein VP39 were present in cells transfected with
38K
knockout bacmids, suggesting that nucleocapsid assembly was interrupted. In contrast, the production of normal nucleocapsids was restored when the
38K
knockout bacmid was rescued with a copy of
38K
. Recombinant virus that expresses 38K fused to green fluorescent protein as a visual marker was constructed to monitor protein transport and localization within the nucleus during infection. Fluorescence was first detected along the cytoplasmic periphery of the nucleus and subsequently localized to the center of the nucleus. These results demonstrate that 38K plays a role in nucleocapsid assembly and is essential for viral replication in the Ac
M
NPV life cycle.
Human Cytomegalovirus Blocks Tumor Necrosis Factor Alpha- and Interleukin-1β-Mediated NF-κB Signaling
Authors: Montag Christina , Wagner Jutta , Gruska Iris , Hagemeier Christian 
Published: November 2006

ABSTRACT
NF-κB plays an important role in the early cellular response to pathogens by activating genes involved in inflammation, immune response, and cell proliferation and survival. NF-κB is also utilized by many viral pathogens, like human cytomegalovirus (HCMV), to activate their own gene expression programs, reflecting intricate roles for NF-κB in both antiviral defense mechanisms and viral physiology. Here we show that the NF-κB signaling pathway stimulated by proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) becomes inhibited in HCMV-infected cells. The block to NF-κB signaling is first noticeable during the early phase of infection but is fully established only at later times. Biochemical and genetic evidence demonstrates that the viral inhibition of proinflammatory signaling by distinct cytokines occurs upstream of the convergence point of NF-κB-activating pathways, i.e., the IκB kinase complex, and that it is mediated via different mechanisms. Consistent with this, we further show that an HCMV variant that has lost the ability to downregulate TNF-α-induced NF-κB signaling also fails to downregulate surface expression of TNF receptor 1, thereby mechanistically linking the inhibition of TNF-α-induced NF-κB signaling by HCMV to TNF receptor targeting. Our data support a model whereby HCMV inhibits cytokine-induced NF-κB signaling at later times during infection, and we suggest that this contributes to the inhibition of the cell's antiviral defense program.
Effects of Picornavirus 3A Proteins on Protein Transport and GBF1-Dependent COP-I Recruitment
Authors: Wessels Els , Duijsings Daniël , Lanke Kjerstin H. W. , van Dooren Sander H. J. , Jackson Catherine L. , Melchers Willem J. G. , van Kuppeveld Frank J. M. 
Published: November 2006

ABSTRACT
The 3A protein of the coxsackievirus B3 (CVB3), an enterovirus that belongs to the family of the picornaviruses, inhibits endoplasmic reticulum-to-Golgi transport. Recently, we elucidated the underlying mechanism by showing that CVB3 3A interferes with ADP-ribosylation factor 1 (Arf1)-dependent COP-I recruitment to membranes by binding and inhibiting the function of GBF1, a guanine nucleotide exchange factor that is required for the activation of Arf1 (E. Wessels et al., Dev. Cell 11:191-201, 2006). Here, we show that the 3A protein of poliovirus, another enterovirus, is also able to interfere with COP-I recruitment through the same mechanism. No interference with protein transport or COP-I recruitment was observed for the 3A proteins of any of the other picornaviruses tested here (human rhinovirus [HRV], encephalomyocarditis virus, foot-and-mouth disease virus, and hepatitis A virus). We show that the 3A proteins of HRV, which are the most closely related to the enteroviruses, are unable to inhibit COP-I recruitment, due to a reduced ability to bind GBF1. When the N-terminal residues of the HRV 3A proteins are replaced by those of CVB3 3A, chimeric proteins are produced that have gained the ability to bind GBF1 and, by consequence, to inhibit protein transport. These results show that the N terminus of the CVB3 3A protein is important for binding of GBF1 and its transport-inhibiting function. Taken together, our data demonstrate that the activity of the enterovirus 3A protein to inhibit GBF1-dependent COP-I recruitment is unique among the picornaviruses.
RhoA-GTPase Facilitates Entry of Kaposi's Sarcoma-Associated Herpesvirus into Adherent Target Cells in a Src-Dependent Manner
Authors: Veettil Mohanan Valiya , Sharma-Walia Neelam , Sadagopan Sathish , Raghu Hari , Sivakumar Ramu , Naranatt Pramod P. , Chandran Bala 
Published: November 2006

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) (human herpesvirus 8) binds to adherent target cell surface heparan sulfate molecules via its envelope glycoproteins gB and gpK8.1A, to integrins via gB, to the transporter CD98/xCT complex, and possibly to another molecule(s). This is followed by virus entry overlapping with the induction of preexisting host cell signal pathways, such as focal adhesion kinase, Src, phosphatidylinositol 3-kinase (PI3-K), Rho-GTPases, protein kinase C-ζ, and extracellular signal-regulated kinase 1/2. Here, using hemagglutinin-tagged plasmids expressing wild-type, dominant-positive, and dominant-negative forms of RhoA in HEK (human embryonic kidney) 293 cells, we investigated the role of RhoA-GTPase in virus entry. The dominant-negative form of RhoA GTPase and treatment of target cells with
Clostridium difficile
toxin B (CdTxB), a specific inactivator of Rho-GTPases, significantly blocked KSHV entry. KSHV infection induced closely similar levels of FAK and PI3-K in all three cell types. In contrast, very strong Src activation was observed in KSHV-infected dominant-positive RhoA cells compared to wild-type cells, and only moderate Src activation was seen in dominant-negative cells. Inhibition of Src activation by CdTxB and reduction of RhoA activation by Src inhibitors suggest that KSHV-induced Src is involved in RhoA activation, which in turn is involved in a feedback-sustained activation of Src. Since the decreased entry in RhoA dominant-negative cells may be due to inefficient signaling downstream of RhoA, we examined the induction of RhoA-activated Dia-2, which is also known to induce Src. Dia-2 coimmunoprecipitated with activated Src, which was inhibited by Src inhibitors, in the infected cells. Together with the reduced virus entry in RhoA dominant-negative cells, these results suggest that activated RhoA-dependent Dia-2 probably functions as a link between RhoA and Src in KSHV-infected cells, mediating the sustained Src activation, and that KSHV-induced Src and RhoA play roles in facilitating entry into adherent target cells.
In Vitro and In Vivo Fitness of Respiratory Syncytial Virus Monoclonal Antibody Escape Mutants
Authors: Zhao Xiaodong , Liu Enmei , Chen Fu-Ping , Sullender Wayne M. 
Published: November 2006

ABSTRACT
Respiratory syncytial virus (RSV) is the only infectious disease for which a monoclonal antibody (MAb) is used in humans. Palivizumab (PZ) is a humanized murine MAb to the F protein of RSV. PZ-resistant viruses appear after in vitro and in vivo growth of RSV in the presence of PZ. Fitness for replication could be a determinant of the likelihood of dissemination of resistant viruses. We assessed the fitness of two PZ-resistant viruses (F212 and MP4). F212 grew less well in cell culture than the parent A2 virus and was predicted to be less fit than A2. Equal amounts of F212 and A2 were mixed and passaged in cell culture. F212 disappeared from the viral population, indicating it was less fit than the A2 virus. The MP4 virus grew as well as A2 in culture and in cotton rats. A2/MP4 virus input ratios of 1:1, 10:1, 100:1, and 1,000:1 were compared in competitive replication. For all input ratios except 1,000:1, the MP4 virus became dominant, supplanting the A2 virus. The MP4 virus also dominated the A2 virus during growth in cotton rats. Thus, the mutant MP4 virus was more fit than A2 virus in both in vitro and in vivo competitive replication. Whether this fitness difference was due to the identified nucleotide substitutions in the F gene or to mutations elsewhere in the genome is unknown. Understanding the mechanisms by which mutant virus fitness increased or decreased could prove useful for consideration in attenuated vaccine design efforts.
Comparison of Avian and Human Influenza A Viruses Reveals a Mutational Bias on the Viral Genomes
Authors: Rabadan Raul , Levine Arnold J. , Robins Harlan 
Published: November 2006

ABSTRACT
In the last few years, the genomic sequence data for thousands of influenza A virus strains, including the 1918 pandemic strain, and hundreds of isolates of the avian influenza virus H5N1, which is causing an increasing number of human fatalities, have become publicly available. This large quantity of sequence data allows us to do comparative genomics with the human and avian versions of the virus. We find that the nucleotide compositions of influenza A viruses infecting the two hosts are sufficiently different that we can determine the host at almost 100% accuracy. This assignment works at the segment level, which allows us to construct the reassortment history of individual segments within each strain. We suggest that the different nucleotide compositions can be explained by a host-dependent mutation bias. To support this idea, we estimate the fixation rates for the different polymerase segments and the ratios of synonymous to nonsynonymous changes. Additionally, we provide evidence supporting the hypothesis that the H1N1 influenza virus entered the human population just prior to the 1918 outbreak, with an earliest bound of 1910.
Cellular Immune Responses in Children and Adults Receiving Inactivated or Live Attenuated Influenza Vaccines
Authors: He Xiao-Song , Holmes Tyson H. , Zhang Caiqiu , Mahmood Kutubuddin , Kemble George W. , Lewis David B. , Dekker Cornelia L. , Greenberg Harry B. , Arvin Ann M. 
Published: November 2006

ABSTRACTThe patterns of cellular immune responses induced by live attenuated influenza vaccine (LAIV) versus those of the trivalent inactivated influenza vaccine (TIV) have not been studied extensively, especially in children. The goals of this study were to evaluate the effects of TIV and LAIV immunization on cellular immunity to live influenza A virus in children and adults and to explore factors associated with variations in responses to influenza vaccines among individuals. A gamma interferon (IFN-γ) flow cytometry assay was used to measure IFN-γ-producing (IFN-γ+) NK and T cells in peripheral blood mononuclear cell cultures stimulated with a live influenza A virus strain before and after LAIV or TIV immunization of children and adults. The mean percentages of influenza A virus-specific IFN-γ+CD4 and CD8 T cells increased significantly after LAIV, but not TIV, immunization in children aged 5 to 9 years. No increases in the mean levels of influenza A virus-reactive IFN-γ+T cells and NK cells were observed in adults given LAIV or TIV. TIV induced a significant increase in influenza A virus-reactive T cells in 6-month- to 4-year-old children; LAIV was not evaluated in this age group. The postvaccination changes (n-fold) in the percentages of influenza A virus-reactive IFN-γ+T and NK cells in adults were highly variable and correlated inversely with the prevaccination percentages, in particular with that of the CD56dimNK cell subset. In conclusion, our findings identify age, type of vaccine, and prevaccination levels of immune reactivity to influenza A virus as factors significantly associated with the magnitude of cellular immune responses to influenza vaccines.
Generation of Filamentous Instead of Icosahedral Particles by Repression of African Swine Fever Virus Structural Protein pB438L
Authors: Epifano Carolina , Krijnse-Locker Jacomine , Salas María L. , Salas José , Rodríguez Javier M. 
Published: November 2006

ABSTRACT
The mechanisms involved in the construction of the icosahedral capsid of the African swine fever virus (ASFV) particle are not well understood at present. Capsid formation requires protein p72, the major capsid component, but other viral proteins are likely to play also a role in this process. We have examined the function of the ASFV structural protein pB438L, encoded by gene B438L, in virus morphogenesis. We show that protein pB438L associates with membranes during the infection, behaving as an integral membrane protein. Using a recombinant ASFV that inducibly expresses protein pB438L, we have determined that this structural protein is essential for the formation of infectious virus particles. In the absence of the protein, the virus assembly sites contain, instead of icosahedral particles, large aberrant tubular structures of viral origin as well as bilobulate forms that present morphological similarities with the tubules. The filamentous particles, which possess an aberrant core shell domain and an inner envelope, are covered by a capsid-like layer that, although containing the major capsid protein p72, does not acquire icosahedral morphology. This capsid, however, is to some extent functional, as the filamentous particles can move from the virus assembly sites to the plasma membrane and exit the cell by budding. The finding that, in the absence of protein pB438L, the viral particles formed have a tubular structure in which the icosahedral symmetry is lost supports a role for this protein in the construction or stabilization of the icosahedral vertices of the virus particle.
The Epstein-Barr Virus-Encoded LMP-1 Oncoprotein Negatively Affects Tyk2 Phosphorylation and Interferon Signaling in Human B Cells
Authors: Geiger Timothy R. , Martin Jennifer M. 
Published: November 2006

ABSTRACTEpstein-Barr virus (EBV) establishes a persistent infection in the human host and is associated with a variety of human cancers. Persistent infection results from a balance between the host immune response and viral immune evasion mechanisms. EBV infection is controlled initially by the innate immune response and later by T-cell-mediated adaptive immunity. EBV has evolved mechanisms to evade the host immune response so that it can persist for the lifetime of the host. Latent membrane protein 1 (LMP-1) is the EBV oncoprotein essential for B-cell immortalization by EBV. We show here that LMP-1 interacts with Tyk2, a signaling intermediate in the alpha interferon (IFN-α) signaling pathway, via a previously uncharacterized LMP-1 signaling domain. LMP-1 prevents Tyk2 phosphorylation and inhibits IFN-α-stimulated STAT2 nuclear translocation and interferon-stimulated response element transcriptional activity. Long-term culture of EBV+lymphoblastoid cells in IFN-α is associated with outgrowth of a population expressing elevated LMP-1 protein levels, suggesting that cells expressing higher levels of LMP-1 survive the antiproliferative selective pressure imposed by IFN-α. These results show that LMP-1 can protect EBV+cells from the IFN-α-stimulated antiviral/antiproliferative response and suggest that chronic IFN-α treatment may encourage the outgrowth of cells expressing elevated, and therefore potentially oncogenic, LMP-1 levels in EBV+individuals.