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At least 829 records · Page 46Linked to original sources
PubMed1998

Temporal transcription of the lactococcal temperate phage TP901-1 and DNA sequence of the early promoter region.

Transcriptional analysis by Northern blotting identified clusters of early, middle and late transcribed regions of the temperate lactococcal bacteriophage TP901-1 during one-step growth experiments. The latent period was found to be 65 min and the burst size 40 +/- 10. The eight early transcripts, all mapping in a 13 kb region adjacent to the attachment site of TP901-1, were present at maximal levels 10 min after infection. The four middle transcripts, observed at maximal levels 30 min after infection, are all located within a 2 kb region at the distal end of the early transcripts. The late class of transcripts were detected 40 min after infection and the amounts of these transcripts increased with time. The late transcripts were localized to the 13 kb region adjacent to the 2 kb middle transcribed region. The sequence of almost 4 kb of the early region was determined, allowing a detailed transcriptional map for the early region of which in total 6.4 kb was sequenced. Sequence analysis of the early region revealed two closely positioned but divergently orientated promoters, PL and PR, in accordance with the orientation of the ORFs and the transcriptional map. Nine ORFs were found, and similarities to a phage repressor, a single-stranded DNA-binding protein, a topoisomerase, a Cro-like protein and two other phage proteins of unknown function were detected. The gene arrangement in the early transcribed region of TP901-1 thus consists of two transcriptional units: one from PR containing four genes, of which at least two (the integrase gene and putative repressor) are needed for lysogeny, and the divergent and longer transcriptional unit from PL, presumably encoding functions required for the lytic life cycle. ORFs with homology to proteins involved in DNA replication were identified on the latter transcriptional unit.

Amino Acid Sequence↗
PubMed2006

Role of the TSG101 gene in Epstein-Barr virus late gene transcription.

Rta, an Epstein-Barr virus (EBV)-encoded immediate-early protein, governs the reactivation of the viral lytic program by transactivating a cascade of lytic gene expression. Cellular transcription factors such as Sp1, ATF2, E2F, and Akt have been demonstrated to mediate Rta transactivation of lytic genes. We report herein that Rta associates with another potent transcription factor, tumor susceptibility gene 101 (TSG101), to promote the activation of EBV late genes. Results from an EBV cDNA array reveal that depletion of TSG101 by siRNA potently inhibits the transcription of five Rta-responsive EBV late genes, BcLF1, BDLF3, BILF2, BLLF1, and BLRF2. Depletion of TSG101 impairs the Rta transactivation of these late promoters severely. Moreover, a concordant augmentation of Rta transactivating activity is observed when TSG101 is overexpressed following ectopic transfection. Mechanistically, Rta interaction with TSG101 causes the latter to accumulate principally in the nuclei, wherein the proteins colocalize and are recruited to the viral promoters. Of note, TSG101 is crucial for the efficient binding of Rta to these late promoters. As a result, cells with defective TSG101 fail to express late viral proteins, leading to a decrease in the yield of virus particles. Thus, the contribution of TSG101 to Rta-mediated late gene activation is of great importance for completion of the EBV productive lytic cycle. These observations consolidate a role for TSG101 in the replication of EBV, a DNA virus, that differs from what is observed for RNA viruses, where TSG101 aids mainly in the endosomal sorting of enveloped late viral proteins for assembly at the plasma membrane.

Base Sequence↗
PubMedDate not supplied

Activity of natural killer cells during HIV-1 infection in Brazilian patients.

UNLABELLED: Natural killer cells are increasingly being considered an important component of innate resistance to viruses, but their role in HIV infection is controversial. Some investigators have found that natural killer cells do not confer a protective effect during the progression of HIV disease, whereas others have shown that natural killer cells may be protective and retard the progression of the disease, either through their lytic activity or by a chemokine-related suppression of HIV replication. In this study, we analyzed functional alterations in the activity of natural killer cells during HIV-1 infection using a natural killer cells activity assay with K562 cells as targets. RESULTS: Our results show that the activity of natural killer cells decreases only in the advanced phase of HIV infection and when high (40:1) effector cell-target cell ratios were used. The depression at this stage of the disease may be related to increased levels of some viral factors, such as gp120 or gag, that interfere with the binding capacity of natural killer cells, or to the decreased production of natural killer cells -activity-stimulating cytokines, such as IFN-a and IL-12, by monocytes, a subset of cells that are also affected in the late stage of HIV infection. The data suggest that decreased natural killer cells cell activity may contribute to the severe impairment of the immune system of patients in the late stages of HIV infection.

Adult↗
PubMed1999

A gamma-herpesvirus sneaks through a CD8(+) T cell response primed to a lytic-phase epitope.

To determine whether established CD8(+) T cell memory to an epitope prominent during the replicative phase of a gamma-herpesvirus infection protects against subsequent challenge, mice were primed with a recombinant vaccinia virus expressing the p56 peptide and then boosted by intranasal exposure to an influenza A virus incorporating p56 in the neuraminidase protein. Clonally expanded populations of functional, p56-specific CD8(+) T cells were present at high frequency in both the lung and the lymphoid tissue 1 month later, immediately before respiratory challenge with gammaHV-68. This prime-and-boost regime led to a massive reduction of productive gammaHV-68 infection in the respiratory tract and, initially, to much lower levels of latency in both the regional lymph nodes and the spleen. The CD8(+) T cell response to another epitope (p79) was diminished, there was less evidence of B cell activation, and the onset of the CD4(+) T cell-dependent splenomegaly was delayed. Within 3-4 weeks of the gammaHV-68 challenge, however, the extent of latent infection in the lymph nodes and spleen was equivalent, and both groups developed the prominent infectious mononucleosis-like syndrome that is characteristic of this infection. The reverse protocol (influenza then vaccinia) seemed to be slightly less effective. Even though immune CD8(+) T cells may be present at the time and site of virus challenge, establishing a high level of CD8(+) T cell memory to lytic-phase epitopes alone does not protect against the longer-term consequences of this gammaHV infection.

Animals↗
PubMed1981

Characterization of herpes simplex virus persistence in a human T lymphoblastoid cell line.

Persistent, dynamic-state infection with herpes simplex virus (HSV) type 1 has been maintained in human T lymphoblastoid (CEM) cells for many months after initial infection with the wild-type virus (HSV0) (input virus/cell multiplicity of 1.0). Persistently infected cells grew as well as uninfected cells, except during occasional periods of crisis (increased viral replication and cytopathic effect). Cells could survive the crisis when they were maintained for twice the usual time interval (8 to 10 rather than 4 to 5 days) before subculture. Interferon was not detectable in the cultures. HSV0 was compared with HSVp1, a small plaque-forming isolate from persistently infected CEM cells. Primary infection of CEM cells with HSV0 at a low input multiplicity (0.01) led to abortive replication, whereas infection with HSVp1 at the same multiplicity resulted in either rapidly lytic or persistent infection depending upon the time interval of subculture. Approximately 55% of plaque-purified clones of HSVp1, as compared with only 5% of HSV0 clones, displayed temperature-sensitive growth in Vero cells. Defective interfering virus was not detectable in uncloned HSVp1 by interference assay. Persistently infected cultures "cured" by treatment with HSV antiserum or incubation at 39 degrees C were resistant to reinfection with HSV but permissive for vesicular stomatitis virus replication, suggesting that these treatments modulated a shift from the dynamic-state of the static-state, latent infection. These studies provide a model for characterization of HSV persistence and latency in a highly differentiated human cell line.

Antibodies, Viral↗
PubMed1997

Inhibition of HIV-1 replication by a Tat transdominant negative mutant in human peripheral blood lymphocytes from healthy donors and HIV-1-infected patients.

It was previously shown that a tat mutant (tat22) where cysteine 22 is substituted by glycine behaves as a transdominant negative mutant in Jurkat T cells lytically or latently infected by HIV-1. In this study we demonstrate that tat22 controls HIV-1 replication in primary cells. This effect was observed both after in vitro infection of peripheral blood mononuclear cells (PBMCs) from normal donors and after reactivation of the latent infection in PBMCs from seropositive patients. The antiviral effect of tat22 was limited to conditions of low virus production. The use of tat22 may be promising for a gene therapy approach to AIDS during the asymptomatic phase of the disease allowing control of virus replication in infected cells and inhibition of virus spread to uninfected cells.

Gene Products, tat↗
PubMed2003

A viral transcriptional activator of Kaposi's sarcoma-associated herpesvirus (KSHV) induces apoptosis, which is blocked in KSHV-infected cells.

Replication and transcription activator (RTA), mostly encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 50, is expressed in the immediate-early phase of reactivation and plays a critical role in inducing the viral lytic cycle in KSHV-infected cells. We established cell clones from BJAB cells and replication-deficient BCBL-1 cells in which KSHV RTA expression was controlled by an inducible promoter of the tetracycline-based Tet-Off expression system. In RTA-inducible BJAB cells, tetracycline removal induced the synthesis of RTA, resulting in cell death. DNA fragmentation, structural changes in the cell membrane, and poly(ADP-ribose) polymerase (PARP) cleavage were observed in the RTA-induced BJAB cells, indicating that RTA expression induced caspase activation and cell death by apoptosis. However, expression of RTA in RTA-inducible BCBL-1 cells did not undergo apoptosis and cell death. These results suggested that KSHV RTA is an apoptosis inducer that is opposed by an antiapoptotic pathway in infected cells.

Animals↗
PubMed1998

The truncated form of the Epstein-Barr virus LMP-1 is dispensable or complimentable by the full-length form in virus infection and replication.

The Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) gene of the Akata virus strain was cloned, and its nucleotide sequence was determined. Compared with the B95-8 strain, the translation initiation codon for the truncated LMP-1 gene, which is expressed in the lytic cycle, was lost. Immunoblotting showed that Akata EBV produces no truncated LMP-1 protein in any state and that the full-length LMP-1 protein is expressed at a significant level during lytic infection. The results suggest that the truncated LMP-1 protein is dispensable for EBV infection and replication or that the full-length form can "functionally" complement the truncated form if the truncated form has a function.

Base Sequence↗
PubMed1977

Effects of temperature and host cell genetic characteristics on the replication of the lipid-containing bacteriophage PR4 in Escherichia coli.

The lipid-containing bacteriophage PR4 is of special intest because it can replicate in various gram-negative bacteria, including Escherichia coli, that carry one of a group of drug resistance plasmids. PR4 grown in E. coli strain PS2R contains about 10% lipid by weight, with the negatively charged phospholipid phosphatidylglycerol being the most abundant lipid in the virion. We now report the following. (i) PR4 attaches to E. coli with an attachment rate constant of Ka approximately 6.2 X 10(-10) ml/min, which is about twice that of the enveloped phage phi6 (to Pseudomonas phaseolicola), but a factor of 5 less than that of phage PM2 (to Pseudomonas BAL-31). (ii) Use of an E. coli glycerol auxotroph indicated that a normal amount of PR4 replication occurs only if glycerol starvation (inhibition of all phospholipid synthesis) begins no earlier than about halfway through the lytic cycle. (iii) Use of an E. coli fatty acid synthesis temperature-sensitive mutant and an E. coli phosphatidylethanolamine synthesis temperature-sensitive mutant indicate that PR4 replication can occur in the absence of either normal fatty acid synthesis or normal phospholipid synthesis if the infection takes place prior to the termination of overall cell growth and the onset of cell death, (iv) Whereas PR4 burst size in nutrient media at 30 degrees C to 42%C is about 40, the burst size at 20 degrees C is less than 3, Temperature-shift experiments show that the temperature late in infection determines the burst size.

Adsorption↗
PubMed2000

Replication of the herpes simplex virus type 1 RL1 mutant 1716 in primary neuronal cell cultures--possible relevance to use as a viral vector.

The herpes simplex virus type 1 (HSV-1) RL1 deletion mutant 1716 has properties that make it a promising candidate as a viral vector for gene therapy in the human nervous system. These properties include its ability to spread along neural pathways and establish a latent infection in post-mitotic neurons, while retaining a non-virulent phenotype in vivo and an inability to cause a lytic infection in stationary or fully differentiated cells. In this study, we used viral replication assays and indirect immunofluorescence to investigate the ability of 1716 to bind to, enter, express genes and produce progeny virus in dissociated neuronal cell cultures prepared from rat hippocampal, medial septal and dorsal root ganglion (DRG) tissues and in primary rat astrocyte cultures. Both heterogeneous cultures and those that had been enriched for neurons were employed. Following both low and high multiplicities of virus infection, the behaviour of 1716 was compared with its wild-type parent HSV-1 strain 17 in these cultures. It was found that the growth of 1716 was significantly impaired compared to wild type HSV-1, with these differences being magnified at lower multiplicities of viral infection as well as in neuron-enriched cultures: this impairment is likely to be due to decreased replication, as immunofluorescence assays showed that 1716 bound to, entered and expressed genes in all neuronal cell types and astrocytes with similar efficiency to the wild type virus. This ability of 1716 to enter and express genes in different neuronal populations demonstrates its potential suitability as a viral vector.

Animals↗
PubMed2001

Spindle cell conversion by Kaposi's sarcoma-associated herpesvirus: formation of colonies and plaques with mixed lytic and latent gene expression in infected primary dermal microvascular endothelial cell cultures.

Angiogenic Kaposi's sarcoma (KS) skin lesions found in both AIDS and non-AIDS patients are universally associated with infection by the presumed causative agent, known as KS-associated herpesvirus (KSHV) or human herpesvirus 8. KSHV genomes expressing latent state virus-encoded mRNAs and the LANA1 (latent nuclear antigen 1) protein are consistently present in spindle-like tumor cells that are thought to be of endothelial cell origin. Although the KSHV lytic cycle can be induced in rare latently infected primary effusion lymphoma (PEL) cell lines, the ability to transmit or assay infectious KSHV has so far eluded investigators. Here, we demonstrate that infection with supernatant virions derived from three different tetradecanoyl phorbol acetate-induced PEL cell lines can induce cultured primary human dermal microvascular endothelial cells (DMVEC) to form colonies of proliferating latently infected spindle-shaped cells, all of which express the KSHV-encoded LANA1 protein. Although their initial infectivity varied widely (JSC1 > > BC3 > BCP1), virions from all three cell lines produced distinctive spindle cell colonies and plaques without affecting the contact-inhibited cobblestone-like phenotype of adjacent uninfected DMVEC. Each infected culture could also be expanded into a completely spindloid persistently infected culture displaying aggregated swirls of spindle cells resembling those in KS lesions. Formation of new colonies and plaques was inhibited in the presence of phosphonoacetic acid or gangciclovir, but these antiherpesvirus agents had little effect on the propagation of already latently infected spindloid cultures. In persistently infected secondary cultures, patches of up to 10% of the spindloid cells constitutively expressed several early viral lytic cycle proteins, and 1 to 2% of the cells also formed typical herpesvirus DNA replication compartments, displayed cytopathic rounding effects, and expressed late viral antigens. We conclude that de novo KSHV infection induces a spindle cell conversion phenotype in primary DMVEC cultures that is directly associated with latent state expression of the LANA1 protein. However, these cultures also spontaneously reactivate to produce an unusual combination of both latent and productive but slow lytic cycle infection. The formation of spindle cell colonies and plaques in DMVEC cultures provides for the first time a quantitative assay for directly measuring the infectivity of KSHV virion preparations.

Antigens, Viral↗
PubMed1997

Conditionally replicating luciferase reporter phages: improved sensitivity for rapid detection and assessment of drug susceptibility of Mycobacterium tuberculosis.

TM4 is a lytic mycobacteriophage which infects mycobacteria of clinical importance. A luciferase reporter phage, phAE40, has been constructed from TM4 and was previously shown to be useful for the rapid detection and drug susceptibility testing of Mycobacterium tuberculosis. However, the lytic nature of the phage results in a loss of detectable light output and limits the sensitivity of detection. We describe several strategies aimed at improving the luciferase activity generated by TM4 luciferase phages, including (i) varying the position of the luciferase gene in the phage genome, (ii) isolating host-range mutants of the phage, and (iii) introducing temperature-sensitive mutations in the phage such that it will not replicate at the infecting temperature. Several new phages generated by these methods show increased intensity of luciferase production compared to the first-generation reporter phage phAE40, and one phage, phAE88, also demonstrates an enhanced duration of luciferase activity. This has allowed the detection of as few as 120 BCG cells and the determination of drug susceptibilities of M. tuberculosis in as little as 1 day.

Bacteriological Techniques↗
PubMed2004

Association between rate of viral genome replication and virulence of Marek's disease herpesvirus strains.

The early pathogenesis of Marek's disease virus (MDV) infection is characterized by a lytic infection followed by the induction of latency. Genetically resistant N2a and susceptible P2a chickens were infected with the less virulent JM-16 or the very virulent plus (vv+) RK-1 MDV strains to examine the relationship between virulence and resistance on virus replication during 1-10 days postinfection (dpi) using real-time quantitative polymerase chain reaction (qPCR) and quantitative reverse transcriptase (qRT)-PCR assays. The numbers of copies of the viral DNA or transcripts amplified by these assays were normalized relative to cellular controls and subjected to three-way ANOVA. Viral DNA but not RNA was present in spleens at 1-3 dpi in decreasing quantities, and at 4 dpi, viral DNA started to increase concomitant with the initiation of viral transcription independently of virus strain and genetic resistance. At 6 dpi, JM-16 became latent in resistant N2a and susceptible P2a chickens with low levels of viral transcripts, but transcriptional activity increased in susceptible P2a chickens at 9 and 10 dpi. In contrast, infection with vv+ RK-1 never went into latency in both chicken lines. Viral transcripts were present from 4 to 10 dpi showing a higher and more persistent viral activity that may lead to severe damage to the lymphoid organs resulting in increased immunosuppression and increased incidence of MD. The use of qPCR and qRT-PCR to determine viral DNA load and transcriptional activity may offer an alternative to the current system of pathotyping to characterize new MDV isolates.

Animals↗
PubMed1986

Nuclear accumulation of HMG1 protein is correlated to DNA synthesis.

The subcellular localization of HMG1 protein was studied by immunoelectron microscopy during growth of CV1 cells in culture and in confluent CV1 cells subsequently lytically infected with SV40. HMG1 was always detected in the cytoplasm of both non-infected and infected cells. On the other hand, this protein displayed a nuclear localization only in those cells active in cellular and/or viral DNA replication, that is, in actively dividing non-infected cells and in confluent cells following SV40 infection. The combination of electron microscope immunocytochemistry and autoradiography revealed that during SV40 lytic infection, HMG1 accumulates at sites of active viral DNA replication. Since HMG1 is a single-stranded DNA binding protein and acts in vitro as a physiological nucleosome assembly factor, we suggest that its presence in the nucleus is related to its requirement in the DNA replication process.

Animals↗
PubMed1998

p53 status does not determine outcome of E1B 55-kilodalton mutant adenovirus lytic infection.

The ability of the adenovirus type 5 E1B 55-kDa mutants dl1520 and dl338 to replicate efficiently and independently of the cell cycle, to synthesis viral DNA, and to lyse infected cells did not correlate with the status of p53 in seven cell lines examined. Rather, cell cycle-independent replication and virus-induced cell killing correlated with permissivity to viral replication. This correlation extended to S-phase HeLa cells, which were more susceptible to virus-induced cell killing by the E1B 55-kDa mutant virus than HeLa cells infected during G1. Wild-type p53 had only a modest effect on E1B mutant virus yields in H1299 cells expressing a temperature-sensitive p53 allele. The defect in E1B 55-kDa mutant virus replication resulting from reduced temperature was as much as 10-fold greater than the defect due to p53 function. At 39 degreesC, the E1B 55-kDa mutant viruses produced wild-type yields of virus and replicated independently of the cell cycle. In addition, the E1B 55-kDa mutant viruses directed the synthesis of late viral proteins to levels equivalent to the wild-type virus level at 39 degreesC. We have previously shown that the defect in mutant virus replication can also be overcome by infecting HeLa cells during S phase. Taken together, these results indicate that the capacity of the E1B 55-kDa mutant virus to replicate independently of the cell cycle does not correlate with the status of p53 but is determined by yet unidentified mechanisms. The cold-sensitive nature of the defect of the E1B 55-kDa mutant virus in both late gene expression and cell cycle-independent replication leads us to speculate that these functions of the E1B 55-kDa protein may be linked.

Adenovirus E1B Proteins↗
PubMed2002

Minimal reactivation of Kaposi's sarcoma-associated herpesvirus by corticosteroids in latently infected B cell lines.

Corticosteroid use in transplant recipients increases the incidence and severity of Kaposi's sarcoma (KS), a disease associated with KS-associated herpesvirus (KSHV) infection. Recently, the prototypic corticosteroid, hydrocortisone, was shown to directly induce lytic cycle reactivation of KSHV in latently-infected BCBL-1 cells. The purpose of this study was to examine this phenomenon in further detail. After incubation with dexamethasone (<or= 30 microM) or hydrocortisone (<or= 30 microM) for 1-4 days, we evaluated KSHV reactivation in latently infected B cell lines (BC-1, BC-3, and BCBL-1) by assessing early-lytic PF-8 and late-lytic gpK8.1 protein expression using flow cytometry. Viral particle production was monitored by quantifying KSHV minor capsid protein levels in cell culture supernatants. A small increase in the percentage of cells expressing viral lytic proteins was observed in BCBL-1, but not in the other cell lines. In combination with 3 nM 12-O-tetradecanoyl-phorbol-13-acetate, a known chemical inducer of KSHV replication, corticosteroids (0.3 microM) enhanced KSHV reactivation twofold in some cell lines, but not in others. In all experiments, lytic viral protein expression by flow cytometry correlated with production of viral particles in culture supernatants. In summary, we found that corticosteroids were limited inducers of KSHV reactivation in latently infected cells. Thus, our findings suggest that corticosteroids do not enhance the incidence and severity of KS in transplant recipients by direct cellular effects on KSHV reactivation.

Adrenal Cortex Hormones↗
PubMed1999

Epstein-barr virus (EBV) nuclear protein 2-induced disruption of EBV latency in the Burkitt's lymphoma cell line Akata: analysis by tetracycline-regulated expression.

The Burkitt's lymphoma (BL) cell line Akata retains the latency I program of Epstein-Barr virus (EBV) gene expression and cross-linking of its surface immunoglobulin G (IgG) by antibodies results in activation of viral replication. When EBV nuclear antigen 2 (EBNA2) was artificially expressed by a constitutive expression vector, the Cp EBNA promoter remained inactive and accordingly the latency III program was not induced. In contrast, expression of LMP2A and activity of the Fp lytic promoter were activated. Consistent with this Fp activity, the rate of spontaneous activation of the EBV replicative cycle was increased significantly, suggesting the possibility that EBNA2 can induce EBV replication. The efficiency of anti-IgG-induced activation of the viral replication was reduced in Akata cells expressing EBNA2. To obtain more direct evidence for EBNA2-induced activation of the EBV replicative cycle, this protein was next expressed by a tetracycline-regulated expression system. EBNA2 was undetectable with low doses (<0.5 microgram/ml) of tetracycline, while its expression was rapidly induced after removal of the antibiotic. This induced expression of EBNA2 was immediately followed by expression of EBV replicative cycle proteins in up to 50% of the cells, as shown by indirect immunofluorescence and immunoblot analysis. These results suggest an unexpected potential of EBNA2 to disrupt EBV latency and to activate viral replication.

Burkitt Lymphoma↗
PubMed1998

Feline CD8+ T cell non-cytolytic anti-feline immunodeficiency virus activity mediated by a soluble factor(s).

Feline immunodeficiency virus (FIV) is more readily isolated from CD8+ T cell-depleted peripheral blood mononuclear cells (PBMC) of FIV-infected cats than from unfractionated PBMC cultures. However, it is not known whether feline CD8+ T cells down-regulate FIV expression by direct interaction with FIV-infected cells or via a soluble mediator. Furthermore, it is not known whether this anti-FIV activity involves a lytic or non-lytic mechanism. In the present study, we demonstrated that autologous and allogeneic CD8+ T cells from asymptomatic FIV-infected cats inhibited the replication of FIV in CD8+ T cell-depleted PBMC cultures in a dose-dependent manner. The inhibitory effect was mediated by a non-lytic mechanism, and was not dependent on direct cell-to-cell contact: an inhibitory effect was exerted by CD8+ T cells across a semi-permeable membrane, and an inhibitory activity was also present in cell-free supernatants from CD8+ T cells. These results suggest that this suppressive effect is mediated, at least in part, by soluble factors produced by CD8+ T cells.

Animals↗