PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Defective Viruses”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1977

Defective Friend spleen focus-forming virus: interfering properties and isolation free from standard leukemia-inducing helper virus.

Defective Friend spleen focus-forming virus (SFFV) is able to interfere with the ability of its naturally occurring leukemia-inducing helper virus (LLV-F) to induce XC plaque formation in several different strains of mouse embryo cells. This interference has been observed by using two different SFFV preparations, one contained in an NB-tropic stock of Friend virus (FV) complex, and the second present in a C57BL-adapted strain of FV complex containing an associated B-tropic LLV-F helper. The LLV-F in NB-tropic FV complex effectively induced XC plaques in C57BL/6 (Fv-1(bb); Fv-2(rr)) mouse embryo fibroblasts (MEF) only in the absence of coinfecting SFFV, indicating that Fv-2-associated resistance to SFFV-induced focus formation in vivo does not necessarily extend to the restriction of SFFV function(s) in vitro (i.e., in Fv-2(rr) C57BL MEF). SFFV interference appears to be an intracellular event since LLV-F can adsorb onto, penetrate, and rescue defective murine sarcoma virus (MSV) from transformed 3T3FL S(+)L(-) cells with equal efficiency in the presence and absence of SFFV. However, significantly fewer LLV-infected S(+)L(-) cells released LLV-F progeny if SFFV was present. These observations suggest that Friend SFFV may be classified as a defective, interfering (DI) particle. Further support for this conclusion has come from studies designed to investigate two physical properties of defective SFFV particles. SFFV layered onto a 0 to 20% sucrose sedimentation gradient was recovered as a symmetrical band of virus that sedimented more slowly than standard LLV-F particles. Pooled SFFV-containing gradient samples contained visualizable type C virus particles and occasionally small amounts of detectable LLV-F. In an attempt to determine the buoyant density of sedimentation gradient-purified SFFV, pooled SFFV samples were layered onto a 25 to 50% sucrose equilibrium density gradient and were centrifuged to equilibrium. Greater than 50% of the infectious SFFV originally layered onto this gradient was recovered and seen as a narrow symmetrical band with peak SFFV infectivity at a sucrose density of 1.14 g/ml. The observed difference between SFFV and LLV-F buoyant densities appears to be related to an inherent physical property of each virus. Mixtures of these two viruses express the buoyant density of that virus population which is in excess in fabricated FV complexes probably due to the formation of SFFV-LLV aggregates. Finally, gradient-purified SFFV failed to induce XC plaques in MEF and did not function to rescue MSV as expected since SFFV itself is replication defective.

Animals↗
PubMed1999

Tamplicon-7, a novel T-lymphotropic vector derived from human herpesvirus 7.

We describe the derivation of a novel T-cell-defective virus vector employing the human herpesvirus 7 (HHV-7). The new vector, designated Tamplicon-7, replicates in CD4(+) T cells. The system is composed of a helper virus and defective virus genomes derived by the replication of the input Tamplicon vector. There are two cis-acting functions required for the replication and packaging of the defective virus genomes in the presence of the helper virus: the viral DNA replication origin and the composite cleavage and packaging signal, which directs the cleavage and packaging of defective virus genomes. Viral DNA replication is compatible with the rolling circle mechanism, producing large head-to-tail concatemers of the Tamplicon vector. Thus, in the presence of the helper virus, the replicated vectors are packaged and secreted into the medium. Furthermore, we have shown that the vector can be employed to express a foreign gene, encoding the green fluorescent protein, in the T cells infected with the HHV-7 helper virus. We predict that the Tamplicon-7 vector might be potentially useful for gene therapy of diseases affecting the human CD4(+) T cells, including autoimmune diseases, T-cell lymphomas, and AIDS.

Base Sequence↗
PubMed1973

Prophylaxis and immunization in mice by use of virus-free defective T particles to protect against intracerebral infection by vesicular stomatitis virus.

Defective interfering T particles of vesicular stomatitis virus provide remarkable protection against viral disease and death when introduced intracerebrally in large numbers along with an otherwise rapidly fatal low dose of standard infectious virus. This profound prophylactic effect of defective T particles is due to homologous autointerference since it is serotype-specific and interferon is not induced. This protective effect can be demonstrated only with preparations of T particles that have been purified completely free of infectious virions. When pure T particles are injected intracerebrally along with large doses of infectious virus, they convert an otherwise rapidly fatal disease process to a slowly progressing virus infection that generally terminates in death after many days of wasting disease and paralysis. Intracerebral injection of virus-free T particles alone is apparently innocuous to mice and stimulates immunity to massive doses of homologous infectious virus. In vitro, virus-free T particles at extremely high multiplicities depress cellular RNA and protein synthesis and kill BHK21 cells in culture, but do not exhibit such effects at moderately high multiplicities.

Animals↗
PubMed2004

Host-specific encapsidation of a defective RNA 3 of Cucumber mosaic virus.

Defective (D) RNAs were generated in tobacco upon passage of two isolates of Cucumber mosaic virus (CMV) initially derived from RNA transcripts of cDNA clones. In both cases, the D RNA was derived by a single in-frame deletion of either 339 or 411 nt within the 3a gene of Fny-CMV RNA 3 or M-CMV RNA 3, respectively. The generation of D RNAs was rare and occurred with two CMV isolates, the virions of which were known to differ in physico-chemical properties. The Fny-CMV D RNA 3, designated D RNA 3-1, was maintained by passage together with Fny-CMV in tobacco, but was lost by passage in squash. D RNA 3-1 accumulated in the inoculated squash cotyledons but not in upper, systemically infected leaves. Virions purified from infected squash cotyledons or leaf mesophyll protoplasts did not contain D RNA 3-1. Therefore, the failure of D RNA 3-1 to accumulate in squash leaves systemically infected by CMV was due to a lack of encapsidation of the D RNA 3-1 and movement out of the inoculated leaves.

Cucumovirus↗
PubMed1991

In vitro homotypic and heterotypic interference by defective interfering particles of West Nile virus.

Defective interfering (DI) particles of the flavivirus West Nile (WN) were generated after as few as two high multiplicity serial passages in Vero and LLC-MK2 cells. Six cell lines (Vero, LLC-MK2, L929, HeLa, BHK-21 and SW13) were used to assay interference by DI particles in a yield reduction assay. Interference was found to vary depending on the cell type used. The highest levels of interference were obtained in LLC-MK2 cells, whereas no detectable effect was observed in BHK-21 and SW13 cells. The ability of DI virus to be propagated varied depending on the cell line used; no detectable propagation of DI virus was observed in SW13 cells. Optimum interference was obtained following co-infection of cells with DI virus and standard virus at a multiplicity of 5. Interference between DI and standard viruses occurred only when they were co-infected or when cells were infected with DI virus 1 h before standard virus. Investigation of heterotypic interference by DI particles of WN virus strains from Sarawak, India and Egypt revealed that interference was dependent on the strain of WN virus or flavivirus used as standard virus. A measure of the similarity between five strains of WN virus and other flaviviruses was made on the basis of interference by DI viruses, and was found to be similar to that based on haemagglutination inhibition tests using a panel of monoclonal antibodies.

Animals↗
PubMed1999

Priming and boosting immunity to respiratory syncytial virus by recombinant replication-defective vaccinia virus MVA.

Intranasal and intramuscular immunizations of mice with the highly attenuated MVA strain of vaccinia virus expressing the respiratory syncytial virus (RSV) F or G glycoprotein induced higher RSV antibody titers than those achieved by infection with RSV and greatly restricted the replication of RS challenge virus in both the upper and lower respiratory tracts. In addition, a recombinant MVA expressing both RSV F and G was stable and was as immunogenic as a combination of two single recombinant viruses. The levels of antibodies to RSV F and G, induced by previous intranasal infection with attenuated RSV, were boosted by intramuscular immunization with recombinant MVA. These data support further development of recombinant MVA as a RSV vaccine.

Animals↗
PubMed1984

Modulation of a systemic Semliki Forest virus infection in mice by defective interfering virus.

Evidence is presented that defective interfering (DI) Semliki Forest virus (SFV) can modulate the systemic infection in mice initiated by intraperitoneal inoculation of 10 LD50 SFV. Either the mean time of death was delayed or mice failed completely to develop any sign of disease. This prophylactic activity of DI virus was not due to the stimulation of an adaptive immune response since an equivalent amount of noninfectious virus antigen did not change the course of disease.

Animals↗
PubMed2003

Yeast as a model host to study replication and recombination of defective interfering RNA of Tomato bushy stunt virus.

Defective interfering (DI) RNA associated with Tomato bushy stunt virus (TBSV), which is a plus-strand RNA virus, requires p33 and p92 proteins of TBSV or the related Cucumber necrosis virus (CNV), for replication in plants. To test if DI RNA can replicate in a model host, we coexpressed TBSV DI RNA and p33/p92 of CNV in yeast. We show evidence for replication of DI RNA in yeast, including (i) dependence on p33 and p92 for DI replication; (ii) presence of active CNV RNA-dependent RNA polymerase in isolated membrane-containing preparations; (iii) increasing amount of DI RNA(+) over time; (iv) accumulation of (-)stranded DI RNA; (v) presence of correct 5' and 3' ends in DI RNA; (vi) inhibition of replication by mutations in the replication enhancer; and (vii) evolution of DI RNA over time, as shown by sequence heterogeneity. We also produced evidence supporting the occurrence of DI RNA recombinants in yeast. In summary, development of yeast as a host for replication of TBSV DI RNA will facilitate studies on the roles of viral and host proteins in replication/recombination.

Base Sequence↗
PubMed1999

Highly efficient induction of protective immunity by a vaccinia virus vector defective in late gene expression.

Vaccinia viruses defective in the essential gene coding for the enzyme uracil DNA glycosylase (UDG) do not undergo DNA replication and do not express late genes in wild-type cells. A UDG-deficient vaccinia virus vector carrying the tick-borne encephalitis (TBE) virus prM/E gene, termed vD4-prME, was constructed, and its potential as a vaccine vector was evaluated. High-level expression of the prM/E antigens could be demonstrated in infected complementing cells, and moderate levels were found under noncomplementing conditions. The vD4-prME vector was used to vaccinate mice; animals receiving single vaccination doses as low as 10(4) PFU were fully protected against challenge with high doses of virulent TBE virus. Single vaccination doses of 10(3) PFU were sufficient to induce significant neutralizing antibody titers. With the corresponding replicating virus, doses at least 10-fold higher were needed to achieve protection. The data indicate that late gene expression of the vaccine vector is not required for successful vaccination; early vaccinia virus gene expression induces a potent protective immune response. The new vaccinia virus-based defective vectors are therefore promising live vaccines for prophylaxis and cancer immunotherapy.

Animals↗
PubMed1978

Characterization of snap-back RNAs in vesicular stomatitis defective interfering virus particles.

VSV defective interfering particles of various sizes and from several independent sources frequently contain plus and minus strand RNA. In many cases some of the complementary strands are covalently linked as snap-back molecules. Infectious particles on the other hand package little or no plus strands. Snap-back molecules from the three different sources examined so far vary in size but appear to conform to the same overall linear duplex structure with cross-links at the ends only. They each contain a base sequence which is a subset of the next larger one and appear to correspond to unique sequences in the L cistron of the genome. Possible origins for these snap-back molecules are discussed.

Defective Viruses↗
PubMed1998

Establishment of MAIDS-defective virus-infected B cell lines and their characterization.

Mice inoculated with the murine AIDS (MAIDS)-defective virus develop severe B and T cell dysfunctions. The primary event in the development of this disease is the infection and polyclonal expansion of the target cells of this defective virus, which have been reported to belong to the B cell lineage. To further study the central role that these cells play in the development of MAIDS, we attempted to establish MAIDS-defective virus-infected B cell lines in vitro. We succeeded in establishing two cell lines, SD1 and CSTB5, from the enlarged organs of C57BL/6 mice inoculated with helper-free stocks of the MAIDS-defective virus. Both cell lines are not transplantable in syngeneic C57BL/6 mice or in nude or CD8-/- mice and are apparently not malignant. They both belong to the B lineage, as their immunoglobulin (Ig) genes, but not the T cell receptor (TcR) beta locus, are rearranged, suggesting that they are relatively mature B cells. However, analysis of cell surface marker expression by FACS revealed a surface phenotype similar to that of pre-B cells (MHC I+, MHC II+, B7.2+, sIgM-, sIgG-, kappa-, B220-, CD5-, Thy1.2-, TcR-, CD3-, CD4-, CD8-, Mac-1-, 33D1-). Additionally, the CSTB5 cells express CD40 and the SD1 cells express CD43. Both cell lines contain the MAIDS-defective provirus and express the expected 4.2-kb viral RNA and the corresponding Pr60gag protein. The CSTB5 cells are nonproducer, while the SD1 cell line produces what appears to be an endogenous MuLV. The phenotype of these cell lines is very similar to what is known about the target B cells of this virus in vivo. These new established cell lines are likely to be useful in elucidating the mechanism(s) by which the MAIDS-defective virus causes its target B cells to proliferate and induce T cell anergy in infected animals.

Animals↗
PubMed1995

Mokola virus glycoprotein and chimeric proteins can replace rabies virus glycoprotein in the rescue of infectious defective rabies virus particles.

A reverse genetics approach which allows the generation of infectious defective rabies virus (RV) particles entirely from plasmid-encoded genomes and proteins (K.-K. Conzelmann and M. Schnell, J. Virol. 68:713-719, 1994) was used to investigate the ability of a heterologous lyssavirus glycoprotein (G) and chimeric G constructs to function in the formation of infectious RV-like particles. Virions containing a chloramphenicol acetyltransferase (CAT) reporter gene (SDI-CAT) were generated in cells simultaneously expressing the genomic RNA analog, the RV N, P, M, and L proteins, and engineered G constructs from transfected plasmids. The infectivity of particles was determined by a CAT assay after passage to helper virus-infected cells. The heterologous G protein from Eth-16 virus (Mokola virus, lyssavirus serotype 3) as well as a construct in which the ectodomain of RV G was fused to the cytoplasmic and transmembrane domains of the Eth-16 virus G rescued infectious SDI-CAT particles. In contrast, a chimeric protein composed of the amino-terminal half of the Eth-16 virus G and the carboxy-terminal half of RV G failed to produce infectious particles. Site-directed mutagenesis was used to convert the antigenic site III of RV G to the corresponding sequence of Eth-16 G. This chimeric protein rescued infectious SDI-CAT particles as efficiently as RV G. Virions containing the chimeric protein were specifically neutralized by an anti-Eth-16 virus serum and escaped neutralization by a monoclonal antibody directed against RV antigenic site III. The results show that entire structural domains as well as short surface epitopes of lyssavirus G proteins may be exchanged without affecting the structure required to mediate infection of cells.

Antigens, Viral↗
PubMed1973

Ribonucleic acid components of murine sarcoma and leukemia viruses.

Defective Kirsten murine sarcoma virus was present as leukemia virus pseudotype [Ki-MSV(MLV)] in a 10- to 100-fold excess over its helper, Kirsten murine leukemia virus (Ki-MLV), when the two viruses were propagated in an NRK rat cell line. The s(omega,20) of the fastsedimenting RNA complex of Ki-MLV and of Ki-MSV-(MLV) was 62 S and 55 S, respectively. Gel electrophoresis in buffered aqueous or formamide solution of the dissociated 62S RNA complex of Ki-MLV showed a single major peak of molecular weight about 2.5 x 10(6). Dissociated 55S RNA of Ki-MSV(MLV) was resolved into a major component with a higher electrophoretic mobility than that of Ki-MLV RNA and molecular weight about 2.3 x 10(6). Occasionally, a minor component with the same electrophoretic mobility as Ki-MLV RNA was observed in Ki-MSV(MLV) RNA; it is thought to be the RNA of Ki-MLV present as helper virus in our stocks of Ki-MSV(MLV). The RNA of an endogenous rat C-type RNA virus was electrophoretically different from both Ki-MLV RNA and Ki-MSV(MLV) RNAs. Oligonucleotide fingerprinting of the RNAs digested with RNase T1 indicated that the RNAs of Ki-MSV(MLV) and Ki-MLV are different. However, the extent of the difference between the two RNAs could not be estimated by this method. The heat-dissociated 50-70S RNAs of two other defective murine sarcoma-leukemia viruses; Harvey-MSV(MLV) and Moloney-MSV(MLV) and of defective spleen-focus-forming Friend virus were resolved electrophoretically into two components. The larger components had the same electrophoretic mobility as the RNA of Ki-MLV or Moloney MLV. The smaller were not present in leukemia virus. It is suggested that the small RNA components of the two murine viruses and of Friend virus represent specific genetic information of these replication-defective transforming viruses. Possible relationships between the RNAs of murine leukemia viruses and replication-defective murine sarcoma and Friend viruses are discussed.

Animals↗
PubMed2000

[Southern blot hybridization analysis for lymphoid neoplasms].

The recent remarkable progress of molecular biology gave us new tools for examination of the etiology and pathology of many diseases. Hence, the introduction of such techniques in our clinical laboratory area is becoming more important and indispensable year by year. In addition to morphological and phenotypical analysis, we are now establishing a molecular diagnosis system to support the clinical diagnosis of hematological malignancies. In the present study, we show our ongoing results focusing on adult T-cell leukemia(ATL). Southern blot analysis for detection of the monoclonal integration of HTLV-I proviral genome, a causative agent of ATL, was performed using digoxigenin-labeled probe. The sensitivity was equivalent to RI-labeled probe and was enough for clinical use. We are also doing Southern blot analysis for immunoglobulin heavy chain gene and T-cell receptor beta chain gene as custom service for the diagnosis of B-lymphoproliferative disorders and non-ATL T-lymphoproliferative disorders. We are reporting such results to the clinical site with our interpretation. Since the band size of the HTLV-I provirus obtained by Southern blot differed in each case and was sometimes smaller than the size of the complete virus, we further analyzed the structure of HTLV-I using long and accurate PCR(LA-PCR) and sequence-target-site PCR(STS-PCR). We found that the integrated HTLV-I provirus is divided into two subtypes, complete virus and defective virus. The incidence of defective virus was high in acute-type ATL compared with that in chronic- or lymphoma-type ATL. Although there are several difficulties in introducing such molecular analyses into the clinical laboratory area, we think that the need is increasing together with the progression of gene therapy and evidence-based medicine.

Blotting, Southern↗
PubMed1984

Modulation of Semliki Forest virus-induced infection of mice by defective-interfering virus.

Preparations of defective-interfering (DI) Semliki Forest virus (SFV) differed qualitatively in their ability to protect mice against lethal SFV-induced encephalitis. The preparations fell into three categories: (1) DI virus p13a protected the majority of mice and left them immune to subsequent challenge with 100 50% lethal doses of SFV; (2) DI virus p4 protected mice to a similar extent, but the susceptibility of all surviving mice to challenge suggested that the protection was mediated without the intervention of the adaptive immune response; and (3) DI virus p5 did not protect mice even though its interference titer was similar to that of the protective preparations. How DI viruses p4 and p13a modulate this lethal infection is not clear; the failure of p4 to stimulate protective immunity suggests that nonadaptive host responses are important, but neither p4 nor p13a altered the course of infection with a heterologous neurotropic virus. Compared with avirulent SFV infection, both DI virus-modulated infections were poorly immunogenic with regard to the humoral immune response, although a minority of mice did have high levels of neutralizing antibody. Other, unknown factors are evidently at work and remain to be elucidated.

Animals↗
PubMed1985

Defective interfering viruses: modulators of infection.

Defective interfering viruses are powerful modulators of infection which can completely alter the manifestation of virus disease or convert the disease into a symptomless infection. Although their structural biochemistry has been widely studied, their biology is still poorly understood, probably because its complexity has been underestimated.

Animals↗