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At least 163 records · Page 9Linked to original sources
PubMed1975

Nonspecific enhancers of resistance in man.

Nonspecific enhancers of resistance may include (1) viral interference, (2) interferon, (3) interferon inducers, (4) bacterial interference, (5) bacterial products such as Coley's "toxins," endotoxins, or staphylococcal, BCG, and Corynebacterium parvum vaccines, (6) transfer factor, and (7) well-defined chemicals such as dinitrochlorbenzene, levamisole, and vitamin C. These are discussed only as they have been applied to man to learn whether or not they have enhanced his ability to resist infections and growth of tumors. Preliminary studies suggest that a variety of relatively safe and effective nonspecific enhancers may soon be available for clinical use.

Adjuvants, Immunologic↗
PubMed1993

Consequences of human immunodeficiency virus type 1 superinfection of chronically infected cells.

Infection of T cell lines by the type 1 human immunodeficiency virus (HIV-1) is associated with downregulation of the CD4 receptor and resistance to further HIV-1 infection, the phenomenon of viral interference. The ACH2 cell line, a model for chronic HIV-1 infection, possesses a single integrated copy of the HIV-1 strain LAI, is essentially CD4 negative, and can be induced to make virus by a variety of stimuli. We utilized the known sequence differences between HIVLAI and HIVRF to devise a polymerase chain reaction (PCR) strategy that permits reliable and quantitative discrimination between the two strains. We demonstrate that ACH2 cells can be superinfected by HIVRF at a frequency of 60-300 HIVRF genomes/10(4) ACH2 cells and that the frequency of superinfection appears to increase with time. Reverse transcription of ACH2 mRNA from days 13, 27, and 38 postinfection allowed a similar PCR strategy (RT-PCR) to be used to analyze full-length HIVRF- and HIVLAI-specific transcripts. These data suggested that superinfection of ACH2 with HIVRF results in an increase in expression of both HIVRF and HIVLAI mRNA. From day 13 to day 38 postinfection there was an increase in the relative expression of HIVRF compared with HIVLAI. By day 38, when only 1.1% of HIV DNA sequences were HIVRF derived, roughly 80% of the HIV-specific full-length mRNA was HIVRF in origin, with a concomitant decrease in HIVLAI transcription.

CD4 Antigens↗
PubMed1997

Adenovirus E1a interferes with expression of vaccinia viral genes.

The 12S and 13S cDNAs of the oncogene E1a encoded by the early region of adenovirus 12 (Ad12) were overexpressed using the T7/encephalomyocarditis (EMC)/vaccinia hybrid expression system. The E1a proteins were stable for at least 12 h in monkey epithelial BSC1 cells. The E1a proteins were recognized by a rabbit polyclonal antibody and displayed phosphorylation patterns similar to those displayed by the E1a proteins expressed in Ad12-transformed cells. Expression of E1a proteins by recombinant vaccinia virus led to inhibition of vaccinia viral protein synthesis which was observed as soon as 6 h after infection. This suppression was mediated by both the 12S and the 13S products of Ad12E1a and to a somewhat lesser extent by the 13S product of Ad2E1a. The inhibition of vaccinia virus gene expression resulted in enhanced survival of vaccinia virus-infected cells. These results suggest that the proteins encoded by the E1a sequester a viral or a cellular product(s) that is essential for the expression of vaccinia virus-encoded genes.

Adenoviridae↗
PubMed1998

The fight of viruses against apoptosis.

The induction of apoptosis of virus-infected cells is an important host defense mechanism against invading pathogens. Some viruses express anti-apoptotic proteins that efficiently block apoptosis induced by death receptors or in response to stress signaled through mitochondria. Viral interference with host cell apoptosis leads to enhanced viral replication and may promote cancer.

Animals↗
PubMed2006

Mass spectrometry reveals specific and global molecular transformations during viral infection.

Mass spectrometry analysis was used to target three different aspects of the viral infection process: the expression kinetics of viral proteins, changes in the expression levels of cellular proteins, and the changes in cellular metabolites in response to viral infection. The combination of these methods represents a new, more comprehensive approach to the study of viral infection revealing the complexity of these events within the infected cell. The proteins associated with measles virus (MV) infection of human HeLa cells were measured using a label-free approach. On the other hand, the regulation of cellular and Flock House Virus (FHV) proteins in response to FHV infection of Drosophila cells was monitored using stable isotope labeling. Three complementary techniques were used to monitor changes in viral protein expression in the cell and host protein expression. A total of 1500 host proteins was identified and quantified, of which over 200 proteins were either up- or down-regulated in response to viral infection, such as the up-regulation of the Drosophila apoptotic croquemort protein, and the down-regulation of proteins that inhibited cell death. These analyses also demonstrated the up-regulation of viral proteins functioning in replication, inhibition of RNA interference, viral assembly, and RNA encapsidation. Over 1000 unique metabolites were also observed with significant changes in over 30, such as the down-regulated cellular phospholipids possibly reflecting the initial events in cell death and viral release. Overall, the cellular transformation that occurs upon viral infection is a process involving hundreds of proteins and metabolites, many of which are structurally and functionally uncharacterized.

Animals↗
PubMed1987

Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICP0 exhibit impaired growth in cell culture.

We report the construction and characterization of deletion mutants in the herpes simplex virus type 1 gene encoding the immediate-early protein ICP0. In the event that ICP0 proved to play an essential role in virus replication, ICP0-transformed Vero cells were generated to serve as permissive hosts for such mutants. Two mutants, dlX0.7 and dlX3.1, were isolated in these cells by a marker rescue-transfer procedure involving the rescue of an ICP4 deletion mutant and the simultaneous insertion of a linked deletion in the ICP0 gene. Mutant dlX0.7 contained a 700-base-pair deletion in both copies of ICP0. The deletion lay entirely within the transcript specified by the gene. dlX0.7 induced the synthesis of an ICP0-specific mRNA that was approximately 0.7 kilobases smaller than the corresponding mRNA specified by wild-type virus. The 3.1-kilobase deletion in both copies of the ICP0 gene in mutant dlX3.1 removed the majority of the transcriptional-regulatory signals and coding sequences, retaining only sequences at the 3' end of the gene. As expected, no ICP0-specific mRNA was detected in dlX3.1-infected Nero cells (G418-resistant Vero cells). Both mutants grew in all cells tested, although their burst sizes were 10- to 100-fold lower than that of wild-type virus. Although the plaque sizes of dlX0.7 and dlX3.1 were equally small on Nero and ICP0-transformed cells, the plating efficiency of the mutants was 15- to 50-fold greater on ICP0-transformed cells than on Nero cells. The mutants exhibited modest interference with the growth of wild-type virus in mixed infections, an effect that was abolished by UV irradiation of the mutants, implying that interference required viral gene expression. Polypeptide profiles generated by the mutants in Nero cells were qualitatively similar to that of wild-type virus. Quantitatively, only slight reductions in the levels of certain late viral polypeptides were observed, a phenomenon also borne out by analysis of viral glycoproteins. Both mutants induced the synthesis of significant, although reduced, levels of viral DNA relative to wild-type virus. Taken together, the results demonstrate that ICP0 is not essential for productive infection in cell culture but that this protein plays a significant role in viral growth, as indicated by the impaired abilities of the mutants to replicate.

Chromosome Deletion↗
PubMed1999

Human DNA oncogenic viruses and their transforming protein interactions with cell cycle control proteins.

PURPOSE: Both oncogenic viruses and cell cycle control proteins are fast-growth research areas. More and more evidence indicates that virus infection and replication are often associated with apoptosis and interfere with cell cycle pathways. To understand the mechanisms by which viral proteins regulate apoptosis and target the cellular pathways may lead to the development of new remedies for some cancers. DATA SOURCES: English literature searched by MEDLINE from January 1995 to August 1998. STUDY SELECTION AND DATA EXTRACTION: More than one hundred research papers published in these areas over the past three years. Only new and important breakthroughs in these papers are selected. The review focuses on DNA viruses associated with the development of human cancers. RESULTS AND CONCLUSIONS: Some DNA viruses contain oncogenic proteins which transform normal cells in vitro and induce tumors in animals. These viral proteins target the cellular pathways and block apoptosis induced by receptors or in response to signal transduction. Viral interference with host cell apoptosis leads to enhanced viral replication and may promote carcinogenesis. Oncogenes and tumor suppressor genes, such as Retinoblastoma (RB) and p53, play important roles in regulation of these interactions.

Animals↗
PubMed1998

Molecular piracy: the viral link to carcinogenesis.

The vast majority of the human experience with viral infections is associated with acute symptoms, such as malaise, fever, chills, rhinitis and diarrhea. With this acute or lytic phase, the immune system mounts a response and eliminates the viral agent while acquiring antibodies to that specific viral subtype. With latent or chronic infections, the viral agent becomes incorporated into the human genome. Viral agents capable of integration into the host's genetic material are particularly dangerous and may commandeer the host's ability to regulate normal cell growth and proliferation. The oncogenic viruses may immortalize the host cell, and facilitate malignant transformation. Cell growth and proliferation may be enhanced by viral interference with tumor suppressor gene function (p53 and pRb). Viruses may act as vectors for mutated proto-oncogenes (oncogenes). Overexpression of these oncogenes in viral-infected cells interferes with normal cell function and allows unregulated cell growth and proliferation, which may lead to malignant transformation and tumour formation. Development of oral neoplasms, both benign and malignant, has been linked to several viruses. Epstein-Barr virus is associated with oral hairy leukoplakia, lymphoproliferative disease, lymphoepithelial carcinoma, B-cell lymphomas, and nasopharyngeal carcinoma. Human herpesvirus-8 has been implicated in all forms of Kaposi's sarcoma, primary effusion lymphomas, multiple myeloma, angioimmunoblastic lymphadenopathy, and Castleman's disease. Human herpesvirus-6 has been detected in lymphoproliferative disease, lymphomas, Hodgkin's disease, and oral squamous cell carcinoma. The role of human papillomavirus in benign (squamous papilloma, focal epithelial hyperplasia, condyloma acuminatum, verruca vulgaris), premalignant (oral epithelial dysplasia), and malignant (squamous cell carcinoma) neoplasms within the oral cavity is well recognized. Herpes simplex virus may participate as a cofactor in oral squamous cell carcinoma development by enhancing activation, amplification, and overexpression of pre-existing oncogenes within neoplastic tissues. Because of the integral role of viruses in malignant transformation of host cells, innovative antiviral therapy may prevent tumour development, involute neoplastic proliferations, or arrest malignant progression.

Cell Division↗
PubMed1984

Viral enhancement and interference induced in cell culture by hepatitis A virus: application to quantitative assays for hepatitis A virus.

Hepatitis A virus (HAV) growing in human diploid lung fibroblast (MRC5) monolayers can either interfere with or enhance the cytopathic effect of Newcastle Disease virus (NDV) challenge. Enhancement of NDV occurred if HAV-infected monolayers were challenged with a low multiplicity of infection of NDV and incubated at 35 degrees C. Interference occurred if HAV-infected monolayers were given a high NDV multiplicity of infection and incubated at 32 degrees C. These phenomena were applied to assays for quantifying HAV and may be useful in providing new insights into viral interference and enhancement.

Antigens, Viral↗
PubMed2004

Preextinction viral RNA can interfere with infectivity.

When the error rate during the copying of genetic material exceeds a threshold value, the genetic information cannot be maintained. This concept is the basis of a new antiviral strategy termed lethal mutagenesis or virus entry into error catastrophe. Critical for its success is preventing survival of residual infectious virus or virus mutants that escape the transition into error catastrophe. Here we document that mutated, preextinction foot-and-mouth disease virus (FMDV) RNA can interfere with and delay viral production up to 30 h when cotransfected in BHK-21 cells with standard RNA. Interference depended on the physical integrity of preextinction RNA and was not observed with unrelated RNAs or with nonmutated, defective FMDV RNA. These results suggest that this type of interference requires large size, preextinction FMDV RNA and is mediated neither by small interfering RNAs nor by RNAs that can compete with infectious RNA for host cell factors. A model based on the aberrant expression of mutated RNA as it is expected to occur in the initial stages of the transition into error catastrophe is proposed. Interference mediated by preextinction RNA indicates an advantage of mutagenesis versus inhibition in preventing the survival of virus escape mutants during antiviral treatments.

Animals↗
PubMed1996

Interference to human immunodeficiency virus type 1 infection in the absence of downmodulation of the principal virus receptor, CD4.

It is thought that interference during human immunodeficiency virus type 1 (HIV-1) infection is established by downmodulation of the principal virus receptor, CD4. Here we present evidence to the contrary. At various times after primary infection, we superinfected T cells in vitro by exposure to a genetically distinct viral clone or to a virus carrying the chloramphenicol acetyltransferase gene. Replication of each virus strain was determined by restriction enzyme analysis of total cellular DNA, by PCR amplification of viral DNA, or by assay of cell extracts for chloramphenicol acetyltransferase activity. We found that efficient viral interference is established within 24 h of infection at a multiplicity of infection of 1. At that time, expression of viral structural proteins was low and infected cells displayed undiminished levels of surface CD4 and were fully susceptible to virus binding and fusion. Superinfection by either cell-free HIV-1 or cocultivation was blocked. Cells resistant to superinfection by HIV-1 remained susceptible to Moloney murine leukemia and vaccinia viruses. No interference was observed 4 h after primary infection or in cells infected with either UV-inactivated HIV-1 or a mutant virus defective in virus-cell fusion activity, indicating that binding of primary virus to CD4 is insufficient to prevent superinfection. The minimum viral requirements for this interference are that HIV-1 must be able to enter cells and synthesize viral DNA; Tat-mediated transcription is dispensable. Our results support the existence of a novel pathway to interference to HIV-1 infection, which we term postentry interference, which blocks superinfection during intracellular phases of the virus life cycle.

Base Sequence↗
PubMed2003

Liver transplantation with hepatitis C virus-infected graft: interaction between donor and recipient viral strains.

Superinfection of different viral strains within a single host provides an opportunity for studying host-virus and virus-virus interactions, including viral interference and genetic recombination, which cannot be studied in infections with single viral strains. Hepatitis C virus (HCV) is a positive single-strand RNA virus that establishes persistent infection in as many as 85% of infected individuals. However, there are few reports regarding coinfection or superinfection of HCV. Because of the lack of tissue culture systems and small animal models supporting efficient HCV replication, we explored these issues in the setting of liver transplantation where both recipient and donor were infected with different HCV strains and therefore represent a distinct model for HCV superinfection. Serial serum samples collected at multiple time points were obtained from 6 HCV-positive liver donor/recipient pairs from the National Institute of Diabetes and Digestive and Kidney Diseases liver transplantation database. At each time point, HCV genotype was determined by both restriction fragment length polymorphism analysis and phylogenetic analysis. Furthermore, we selectively sequenced 3 full-length HCV isolates at the earliest time points after liver transplantation, including both 5' and 3' ends. Detailed genetic analyses showed that only one strain of HCV could be identified at each time point in all 6 cases. Recipient HCV strains took over in 3 cases, whereas donor HCV strains dominated after liver transplantation in the remaining 3 cases. In conclusion, in all 6 cases studied, there was no genetic recombination detected among HCV quasispecies or between donor and recipient HCV strains.

Adult↗
PubMed1988

Variants of amphotropic type-C retrovirus isolated from cultures of Moloney- and Rauscher-MuLV-induced tumors.

We isolated and characterized 2 strains of type-C retrovirus, R5NX and YACNX, from established lymphoid cell cultures derived from Rauscher-MuLV-induced lymphoma (RBL-5) in a C57BL/6 mouse, and Moloney-MuLV-induced lymphoma (YAC) in an A-strain mouse, respectively. The R5NX and YACNX viruses were compared with the prototype 4070A strain of amphotropic virus isolated from feral mice in California, and were found to belong to the same amphotropic virus class on the basis of viral interference, neutralization tests, and other biological properties. However, they were not quite identical with respect to viral neutralization antigens and restriction enzyme cleavage patterns of the proviral DNA. The possibility that these viruses may have been present in the original tumor together with the R-MuLV or M-MuLV as "exogenous" viruses rather than as contaminants of cell cultures by the 4070A virus is discussed. Although these 2 isolates were not pathogenic when inoculated into newborn C3H/HE mice, they could establish persistent infections in these mice.

Animals↗
PubMed2006

Manipulation of the nuclear factor-kappaB pathway and the innate immune response by viruses.

Viral and microbial constituents contain specific motifs or pathogen-associated molecular patterns (PAMPs) that are recognized by cell surface- and endosome-associated Toll-like receptors (TLRs). In addition, intracellular viral double-stranded RNA is detected by two recently characterized DExD/H box RNA helicases, RIG-I and Mda-5. Both TLR-dependent and -independent pathways engage the IkappaB kinase (IKK) complex and related kinases TBK-1 and IKKvarepsilon. Activation of the nuclear factor kappaB (NF-kappaB) and interferon regulatory factor (IRF) transcription factor pathways are essential immediate early steps of immune activation; as a result, both pathways represent prime candidates for viral interference. Many viruses have developed strategies to manipulate NF-kappaB signaling through the use of multifunctional viral proteins that target the host innate immune response pathways. This review discusses three rapidly evolving areas of research on viral pathogenesis: the recognition and signaling in response to virus infection through TLR-dependent and -independent mechanisms, the involvement of NF-kappaB in the host innate immune response and the multitude of strategies used by different viruses to short circuit the NF-kappaB pathway.

Animals↗
PubMed2001

Activation of interferon response factor-3 in human cells infected with herpes simplex virus type 1 or human cytomegalovirus.

Activation of cellular interferon-stimulated genes (ISGs) after infection with herpes simplex virus type 1 (HSV-1) or human cytomegalovirus (HCMV) was investigated. The level of ISG54-specific RNA in human fetal lung (HFL) or human foreskin (BJ) fibroblasts increased substantially after infection with either virus in the presence of cycloheximide. HSV-1 particles lacking glycoprotein D or glycoprotein H failed to induce ISG54-specific RNA synthesis, demonstrating that entry of virus particles rather than binding of virions to the cell surface was required for the effect. A DNA-binding complex that recognized an interferon-responsive sequence motif was induced upon infection with HSV-1 or HCMV in the presence of cycloheximide, and the complex was shown to contain the cell proteins interferon response factor 3 (IRF-3) and CREB-binding protein. IRF-3 was modified after infection with HSV-1 or HCMV to a form of lower electrophoretic mobility, consistent with phosphorylation. De novo transcription of viral or cellular genes was not required for the activation of IRF-3, since the effect was not sensitive to inhibition by actinomycin D. Infection of HFL fibroblasts with HSV-1 under conditions in which viral replication proceeded normally resulted in severely reduced levels of the IRF-3-containing complex, defining the activation of IRF-3 as a target for viral interference with ISG induction. In BJ fibroblasts, however, significant activation of IRF-3 was detected even when the viral gene expression program progressed to later stages, demonstrating that the degree of inhibition of the response was dependent on host cell type. As a consequence of IRF-3 activation, endogenous interferon was released from BJ cells and was capable of triggering the appropriate signal transduction pathway in both infected and uninfected cells. Activation of ISG54-specific RNA synthesis was not detected after infection of human U-373MG glioblastoma cells, showing that the induction of the response by infection is cell type dependent.

Apoptosis Regulatory Proteins↗
PubMed1998

Characterization of a live-attenuated retroviral vaccine demonstrates protection via immune mechanisms.

Live-attenuated retroviruses have been shown to be effective retroviral vaccines, but currently little is known regarding the mechanisms of protection. In the present studies, we used Friend virus as a model to analyze characteristics of a live-attenuated vaccine in protection against virus-induced disease. Highly susceptible mice were immunized with nonpathogenic Friend murine leukemia helper virus (F-MuLV), which replicates poorly in adult mice. Further attenuation of the vaccine virus was achieved by crossing the Fv-1 genetic resistance barrier. The minimum dose of vaccine virus required to protect 100% of the mice against challenge with pathogenic Friend virus complex was determined to be 10(3) focus-forming units of attenuated virus. Live vaccine virus was necessary for induction of immunity, since inactivated F-MuLV did not induce protection. To determine whether immune cells mediated protection, spleen cells from vaccinated donor mice were adoptively transferred into syngeneic recipients. The results indicated that immune mechanisms rather than viral interference mediated protection.

Animals↗
PubMed1979

Defective influenza viral ribonucleoproteins cause interference.

Ribonucleoproteins (RNPs) isolated from infectious and defective interfering (DI) influenza virus (WSN) contained three major RNP peaks when analyzed in a glycerol gradient. Peak I RNP was predominant in infectious virus but was greatly reduced in DI virus preparations. Conversely, peak III RNP was elevated in DI virus, suggesting a large increase in DI RNA in this fraction. Labeled [(32)P]RNA was isolated from each RNP region and analyzed by electrophoresis on polyacrylamide gels. Peak I RNP contained primarily the polymerase and some HA genes, peak II contained some HA gene but mostly the NP and NA genes, and peak III contained the M and NS genes. In addition, peak III RNP from DI virus also contained the characteristic DI RNA segments. Interference activity of RNP fractions isolated from infectious and DI virus was tested using infectious center reduction assay. RNP peaks (I, II, and III) from infectious virus did not show any interference activity, whereas the peak III DI RNP caused a reduction in the number of infectious centers as compared to controls. Similar interference was not demonstrable with peak I RNP of DI virus nor with any RNP fractions from infectious virus alone. The interference activity of RNP fractions was RNase sensitive, suggesting that the DI RNA contained in DI RNPs was the interfering agent, and dilution experiments supported the conclusion that a single DI RNP could cause interference. The interfering RNPs were heterogeneous, and the majority migrated slower than viral RNPs containing M and NS genes. These results suggest that DI RNP (or DI RNA) is also responsible for interference in segmented, negative-stranded viruses.

Defective Viruses↗