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At least 145 records · Page 8Linked to original sources
PubMed1991

High resolution in situ hybridization to determine the cellular distribution of lymphocytic choriomeningitis virus RNA in the tissues of persistently infected mice: relevance to arenavirus disease and mechanisms of viral persistence.

By the application of in situ hybridization to thin sections of paraffin-embedded tissues we have been able to determine with high resolution the cell types containing lymphocytic choriomeningitis virus nucleic acid in the tissues of persistently infected mice. We confirm and extend previous observations of virus persistence in the brain, lung, liver, kidney, pancreas, thyroid and reticuloendothelial system. In addition, we demonstrate for the first time persistence of viral nucleic acid in specific cell types in the thymus, lymph nodes, testes and bladder, and the adrenal, parathyroid and salivary glands; the cell types infected were observed in several animals. In lymphoid tissue, viral nucleic acid was predominantly located in the T cell-dependent areas of the spleen and lymph nodes; it was also present in cells of the thymic medulla. This has important implications for the deficiency in T cell function observed in persistently infected mice. In the testes, viral nucleic acid was detected in spermatogonia but not differentiating spermatocytes and therefore, in this tissue at least, persistence is related to the state of differentiation of the cell. Endocrine and exocrine dysfunctions have been described in persistently infected mice and we report that the highest levels of viral nucleic acid were found in the adrenal gland. The infection of endocrine and exocrine tissue was not pantropic, specific cell types expressed viral nucleic acid in each tissue. In the adrenal cortex, cells of the zona reticularis and zona fasciculata but not the zona glomerulosa were positive, whereas in the adrenal medulla viral nucleic acid was predominantly localized to adrenalin-secreting cells. Infection of the renal tubules, transitional epithelium of the bladder and the ducts of the salivary gland indicates the likely sites of virus production for the dissemination of arenavirus infections.

Adrenal Glands↗
PubMed2006

Defective interfering RNAs of Japanese encephalitis virus found in mosquito cells and correlation with persistent infection.

Defective interfering (DI) RNAs are deletion mutants of viral genomes that are known in many cases to contribute to persistent infection and modification of viral pathogenesis. Cell type also plays a critical role in the establishment of viral persistence. In this study we have identified for the first time the generation of DI RNAs of Japanese encephalitis virus in C6/36 mosquito cells. A persistent infection was established by replacing growth medium on surviving cells and continued cell passaging. Persistent infection was demonstrated by a continual release of infectious virus, fluorescent antibody staining, and Northern analysis. A population of DI RNAs of approximately 8.2-9.7 kb, not detectable in acutely infected cells, became apparent in the persistently infected cells by 25 days postinfection. Sequence analyses revealed a population of DI RNAs that contained in-frame deletions of 1.3-2.8 kb covering the region of the E gene and some flanking C or prM and NS1 gene sequences. Transcripts from one cDNA clone of a DI RNA replicated in uninfected mosquito cells as demonstrated by RT-PCR. DI RNA-containing virions in supernatant fluids from persistently infected mosquito cells could be used to establish persistent infection in BHK-21 cells. The correlation of DI RNA presence with cell survival suggests that DI RNAs are contributing mechanistically to the establishment of persistent infection in both the mosquito and mammalian cells.

Animals↗
PubMed1990

Viral RNA and protein synthesis in two LLC-MK2 cell lines persistently infected with human parainfluenza virus 3.

Two lines of LLC-MK2 cells persistently infected with human parainfluenza virus 3 (HPIV-3) have been maintained in culture for approximately 3 years. Subgenomic RNAs (putative defective interfering particle genomes) were detected in virions released from both persistently infected cultures. In one of the persistently infected cell lines cyclic variation in the production of virions containing standard virus genomic-size (50S) RNA and subgenomic RNA was observed. The molar ratio of subgenomic RNA to 50S RNA ranged from less than 0.1/1 to 8.7/1. Northern blot analyses revealed that the patterns of viral mRNA synthesis in persistently infected cells from both cultures were similar to those of standard virus infected cells. Furthermore, the intracellular viral-specific proteins had electrophoretic mobilities similar to the corresponding proteins in standard virus-infected cells. Nucleotide sequence analysis of cloned M gene from virus after 29 months of persistence (147 passages) revealed only one variable conservative amino acid change in two clones analyzed from each cell line, indicating that the M protein is not likely to be involved in the maintenance of the persistent infections. The possible mechanisms by which the persistent state is maintained are discussed.

Cell Line↗
PubMed1998

Critical role for CD4(+) T cells in controlling retrovirus replication and spread in persistently infected mice.

Reactivations of persistent viral infections pose a significant medical problem in immunocompromised cancer, transplant, and AIDS patients, yet little is known about how persistent viral infections are immunologically controlled. Here we describe a mouse model for investigating the role of the immune response in controlling a persistent retroviral infection. We demonstrate that, following recovery from acute Friend virus infection, a small number of B cells evade immunological destruction and harbor persistent virus. In vivo depletions of T-cell subsets in persistently infected mice revealed a critical role for CD4(+) T cells in controlling virus replication, spread to the erythroid lineage, and induction of erythroleukemia. The CD4(+) T-cell effect was independent of CD8(+) T cells and in some cases was also independent of virus-neutralizing antibody responses. Thus, the CD4(+) T cells may have had a direct antiviral effect. These results may have relevance for human immunodeficiency virus (HIV) infections where loss of CD4(+) T cells is associated with an increase in HIV replication, reactivation of persistent viruses, and a high incidence of virus-associated cancers.

Animals↗
PubMed2001

[Long-term results after resection arthroplasty according to Girdlestone for treatment of persisting infections of the hip joint].

INTRODUCTION: Persisting infections of the hip joint are regarded as one of the most feared complications following total hip arthroplasty or failed osteosynthetic treatment of fractures of the proximal femoral part. In these cases resection arthroplasty according to Girdlestone often is the ultimate treatment. METHODS: Twenty-seven patients (11 men and 16 women) who had undergone resection arthroplasty according to Girdlestone could be included in this study. In all cases Girdlestone operations had been performed because of persisting infections of the hip joint. The mean follow-up was 7.1 years. RESULTS: In 22 out of 27 cases (81.5%) eradication of the infection was finally achieved. At the time of re-evaluation 6 patients had no pain, 12 sometimes suffered from moderate pain, 7 from pain during physical activities and 2 patients experienced pain even at rest. At the time of follow-up, 11 patients used a cane, 14 patients needed two canes or crutches and in 2 cases a wheelchair was necessary. The mean shortening of the leg was 5.2 cm (range 3-15 cm). Clinical evaluation using the score according to Merle d'Aubigné and Postel to assess the functional results showed a mean of 6.7 points (range 2-10 points). Of our patients, 59.3 % were satisfied with the functional results obtained. CONCLUSION: In the long run the Girdlestone procedure still seems to be a reasonable salvage operation for persisting deep infections following hip surgery.

Activities of Daily Living↗
PubMed1993

Cytotoxic T lymphocytes cleanse viral gene products from individually infected neurons and lymphocytes in mice persistently infected with lymphocytic choriomeningitis virus.

Lymphocytes and/or monocytes/macrophages carry viral genetic information in most, if not all, persistent and latent viral infections, and serve as potential reservoirs for maintaining or reintroducing the infection. Similarly, neurons can be persistently infected by several DNA and RNA viruses whose continued presence can alter the physiologic function of these cells, leading to disorders in neurotransmitters and disease. Here, we document that adoptive transfer of virus-specific cytotoxic T lymphocytes clears virus and viral nucleic acid sequences, in vivo, from individually infected lymphocytes, macrophages, and neurons. By plaquing, infectious center, Northern blot, and in situ hybridization at the single cell level, virus was efficiently removed from these cells.

Animals↗
PubMed1976

Role of temperature-sensitive mutants in persistent infections initiated with vesicular stomatitis virus.

Noncytocidal persistent infections at 37 C of mouse L cells (Lvsv) with infective B particles of vesicular stomatitis virus (VSV) could be established only in the presence of large numbers of defective interfering (DI) particles. Under these conditions, there was a rapid spontaneous selection of temperature-sensitive (ts) virus. At 10 days there was an increase to 17.8% in the frequency of ts clones in the virus population; by 17 days this frequency had reached 85.2%, and by 63 days 100% of the clones isolated were ts at 39.5 C, the nonpermissive temperature used. All 34 of the clones isolated from the 84-day fluid had an RNA-phenotype, and 8 clones that were tested all belonged to VSV complementation group I. When tested by an interference assay, Lvsv fluids did not contain significant numbers of DI particles (less than 1 DI/PFU). Furthermore, persistent infection of L cells at 37 C could be initiated under conditions in which few, if any, DI particles were present by using low input multiplicities (10(-4) and 10(-5) of a clonal isolate of an RNA-group I mutant obtained from Lvsv cells. On the basis of these and other results, a mechanism is proposed to explain the role of ts mutants in both the establishment and maintenance of the persistently infected state.

Bromodeoxyuridine↗
PubMed1980

Polypeptide synthesis in alphavirus-infected Aedes albopictus cells during the establishment of persistent infection.

Polypeptide synthesis was examined in mosquito cells during the establishment of a persistent infection with two alphaviruses, Ross River virus (RRV) and Semliki Forest virus (SFV), and in vertebrate cells cytopathically-infected with the same viruses. In Aedes albopictus cell, RRV reached peak titres at 34--48 hours p.i. At 12 hours 85 per cent of cells assayed as infected by infective centre assay; by 48 hours when persistence was established, virus production was reduced and less than 5 per cent of cells assayed as infected. There was no shut-down of host polypeptide synthesis during infection. Viral polypeptide synthesis was maximal between 10 and 24 hours p.i. The major viral polypeptides labelled were nucleocapsid protein and envelope protein(s). The precursor polypeptide p95 which was prominent in infected BHK cells was not detected in mosquito cells. Similar results were obtained on SFV infection. During the establishment of persistence there was a coordinate decline in the synthesis of RRV polypeptides, reaching undetectable levels by 72 hours p.i. Subculturing persitently-infected cells led to a small increase in viral polypeptide synthesis and virus titre. In contrast, during RRV growth in BHK celos host protein synthesis was severly inhibited and by 9--11 hours p.i. virus-specific polypeptide synthesis represented more than 90 per cent of total protein synthetic activity.

Aedes↗
PubMed1981

Attachment defect in mouse fibroblasts (L cells) persistently infected with Chlamydia psittaci.

Almost all the cells in populations of mouse fibroblasts (L cells) persistently infected with the 6BC strain of Chlamydia psittaci were immune to superinfection with high multiplicities of C. psittaci, whether or not the L cells contained visible chlamydial inclusions. As ascertained by experiments with 14C-labeled C. psittaci, immunity to superinfection resulted from the failure of added chlamydiae to attach to persistently infected host cells. However, when exogenous C. psittaci was introduced into persistently infected L cells by centrifuging the inoculum onto host cell monolayers or by pretreating the monolayers with diethylaminoethyl-dextran, these chlamydiae produced expected numbers of infectious progeny. Persistently infected L cells were associated in an unknown way with a C. psittaci population that entered the host cells only with the aid of centrifugation or pretreatment with diethylaminoethyl-dextran. Inclusion-free, persistently infected L cells appeared to present at least two separate hindrances to chlamydial activity: blockage of the attachment of exogenous elementary bodies to persistently infected host cells and prevention of the initiation of chlamydial multiplication by means of a normal developmental cycle in the absence of added C. psittaci.

Animals↗
PubMed1995

Effect of surface antigen-1 (SA-1) immune lymphocyte subsets and naive cell subsets in protecting scid mice from initial and persistent infection with Cryptosporidium parvum.

We tested the hypothesis that adoptive transfer of immune spleen cell subsets from Cryptosporidium parvum antigen immunized, immunocompetent BALB/c mice would prevent initial infection or terminate persistent infection in severe combined immunodeficient (scid) mice. Cell donor mice were immunized with either solubilized C. parvum oocysts and sporozoites (positive control) or a surface antigen-1 (SA-1) enriched C. parvum antigen fraction. Both groups of BALB/c cell donor mice immunized with C. parvum antigens had increased antibody titers and lymphoproliferative responses when compared with negative control mice injected with phosphate buffered saline and adjuvant. Intravenous adoptive transfer of 5 x 10(6) cells of each cell subset (spleen cells, CD4 T and B lymphocytes, CD4 T lymphocytes or B lymphocytes) derived from immunized adult BALB/c donor mice did not protect scid mice against initial infection of the gastrointestinal epithelium with C. parvum, despite flow cytometric evidence of CD4 T lymphocyte engraftment in the spleen and detectable levels of C. parvum-specific serum antibody. In contrast, intravenous injection of either naive or immune CD4 T and B lymphocytes combined, or CD4 T lymphocytes alone, terminated persistent C. parvum infection in scid mice. Intestinal infectivity scores were significantly reduced by 9 days post-engraftment in all groups and continued to decline throughout the remainder of the experiment. Flow cytometric analysis demonstrated significantly increased CD4 T lymphocytes in the spleens of recipient scid mice when compared with infected scid mice receiving no cells. Cryptosporidium parvum-specific antibody was detected on day 12 post engraftment in mice receiving SA-1 immune CD4 T and B lymphocytes but was not detectable in mice receiving naive cell subsets.

Animals↗
PubMed1980

[Studies on establishment and maintenance of persistent infection with measles virus in NC-37 cell. 1. Production of DNA-synthesis-suppressing factor (DSF) in NC-37 cell infected with measles virus].

Wild strains of measles virus, such as Edmonston, Toyoshima and freshly isolated KM strain which had not a capacity to establish a persistent infection in NC-37 cell inhibited 80-90 percent of host cellular DNA synthesis, while attenuated or subacute sclerosing panencephalitis (SSPE) viruses, such as Schwarz, Halle and Mantooth which had a capacity to establish persistent infection inhibited about 50 percent of host cellular DNA synthesis 6 or 7 days after infection of virus. However, inhibition of DNA synthesis in cells infected with attenuated or SSPE virus recovered gradually to the same level of control cell within two weeks after infection of virus, and persistently infected cells were not suppressed cellular DNA synthesis in synchronized cell culture. NC-37 cells infected with wild strain produced host cellular DNA-synthesis-suppressing factor (DSF) into culture fluid, but it could detect no such factor in culture fluid of cells infected with attenuated, SSPE virus, or carried virus and persistently infected cell. Furthermore, persistently infected cell treated wtih DSF caused the suppression of DNA synthesis, and so these cells died of metabolic inhibition within one week after inoculation of DSF. NC-37 cell infected with Mantooth strain was inhibited the establishment of persistent infection by the treatment of cell with DSF.

Cells, Cultured↗
PubMedDate not supplied

[Alphavirus reproduction in cultures of transplantable human lymphoblastoid cells during persistent infections].

The results of virological investigations of alphavirus persistence in human B-cell lines Raji and L-101 are presented. The formation of persisting infection was shown to depend both on the cell line and on the virus type. Productive persistent infection of Raji cells with Venezuelan equine encephalitis virus was followed for 11 months. The presence of the virus was confirmed by electron microscopic and immunofluorescent examinations. Infectious virus production varied from 0.001 to dozens PFU/cell, and the content of viable cells from 100,000 to 300,000 in 1 ml of the culture fluid. Virus infectivity in the culture medium varied within the range of 5-7 lg PFU/ml. Human lymphoblastoid cells Raji persistently infected with Venezuelan equine encephalitis virus were examined cytologically, karyologically, and electron microscopically. The long-term presence of the virus resulted in profound alterations in the cell population. Morphology of the cells and processes of division were changed, the mitotic index decreased, the rate of 3H-thymidine incorporation into cellular DNA increased. The mechanisms of persistence are discussed.

B-Lymphocytes↗
PubMed1986

Persistent infection of chimpanzees with human T-lymphotropic virus type III/lymphadenopathy-associated virus: a potential model for acquired immunodeficiency syndrome.

The lymphadenopathy-associated virus (LAV) prototype strain of human T-lymphotropic virus type III/LAV was transmitted to juvenile chimpanzees with no prior immunostimulation by (i) intravenous injection of autologous cells infected in vitro, (ii) intravenous injection of cell-free virus, and (iii) transfusion from a previously infected chimpanzee. All five animals that received more than one 50% tissue culture infective dose were persistently infected with LAV or chimpanzee-passaged LAV for up to 18 months. During this time they developed no illnesses, but they exhibited various degrees of inguinal and axillary lymphadenopathy and significant reductions in rates of weight gain. Detailed blood chemistry and hematologic evaluations revealed no consistent abnormalities, with the exception of immunoglobulin G (IgG) hypergammaglobulinemia, which became apparent in one animal 6 months postinfection and continued at more than 1 year postinfection. Transient depressions followed by increases in the numbers of T4 cells to levels greater than normal were observed in all animals after virus inoculation. However, the number of LAV-infected peripheral blood cells decreased with time after infection. Results of enzyme immunoassays showed that all infected animals seroconverted to IgG anti-LAV within 1 month postinfection and that antibody titers remained high throughout the period of observation. In contrast, only three of the five LAV-infected chimpanzees had detectable IgM antibody responses, and these preceded IgG-specific serum antibodies by 1 to 2 weeks. Virus morphologically and serologically identical to LAV was isolated from peripheral blood mononuclear cells of all infected animals at all times tested and from bone marrow cells taken from one animal 8 months after infection. One chimpanzee that was exposed to LAV only by sharing a cage with an infected chimpanzee developed lymphadenopathy and an IgM response to LAV, both of which were transient; however, no persistent IgG antibody response to LAV developed, and no virus was recovered from peripheral blood cells during a year of follow-up. Thus, LAV readily infected chimpanzees following intravenous inoculation and persisted for extended periods despite the presence of high titers of antiviral antibodies. However, the virus was not easily transmitted from infected to uninfected chimpanzees during daily cage contact.

Acquired Immunodeficiency Syndrome↗
PubMed1978

General features of persistent virus infections.

Persistent virus infections are discussed from the virus point of view in terms of the bodily sites in which the infection persists. Glands and body surfaces are thought to be significant because they give the virus protection at the topographical level from immune forces, and because they are appropriate sites for the shedding of virus to the exterior. Germ cells are relevant sites because infection can thus be transmitted vertically from generation to generation in the host. The central nervous system, however, is generally a 'dead end' from which there is no shedding to the exterior. Persistance in blood may be relevant when continued arthropod transmission becomes possible. Most persistent viruses infect lymphoreticular tissues, and this is interpreted by suggesting that it results in an impaired immune response to the infecting virus, which in turn favours persistence. It is suggested that the biological function of virus transformation and the integration of viral into host cell DNA is that it enables the infection to persist in the host and undergo reactivation. Papovaviruses, adenoviruses and oncornaviruses are considered from this point of view.

Adenoviridae Infections↗
PubMed1996

Expression of tissue factor is increased in astrocytes within the central nervous system during persistent infection with borna disease virus.

Persistent tolerant infection of rats with borna disease virus (BDV) results in a central nervous system (CNS) disease characterized by behavioral abnormalities. These disorders occur without inflammation and widespread cytolysis in the CNS. Therefore, mechanisms other than virally induced destruction of brain cells may explain the CNS disturbance caused by BDV. Previously, we have shown that astrocytes in the CNS express tissue factor (TF). TF functions as the primary cellular initiator of the coagulation protease cascades, resulting in the generation of the protease thrombin. Proteases and their inhibitors play important roles in the development and physiology of the CNS, and altered protease activity has been implicated in the pathophysiology of various neurological diseases. Here, we present evidence that TF expression in the brain is markedly increased during persistent infection with BDV. Persistent infection of cultured astrocytes with BDV also increased TF expression as a result of both increased transcription of the TF gene and stabilization of TF mRNA. We speculate that increased TF expression within the brain parenchyma may lead to increased protease activity in the CNS and contribute to virus-mediated CNS functional impairment by affecting neural cell interactions.

Animals↗
PubMed1986

Tumorigenicity of persistently infected tumors in nude mice is a function of both virus and host cell type.

Although BHK-21 cells persistently infected with wild-type vesicular stomatitis virus (VSV) are sensitive to natural killer (NK) cells and do not form tumors in athymic nude mice, BHK-21 cells persistently infected with a previously isolated mutant virus (VSV-P) are resistant to NK cells and form tumors in nude mice. We used this VSV-P mutant to persistently infect HeLa cells and mouse tumor cell lines. A mouse mastocytoma line (P815) persistently infected with VSV-P was similar to BHK-21 cells in that it was resistant to NK cell lysis and formed tumors in nude mice. However, neither HeLa cells nor mouse myeloma lines persistently infected with VSV-P were resistant to NK cell lysis in vitro, and neither formed tumors in nude mice. Rejection by nude mice of HeLa cells and mouse myeloma cell lines persistently infected with VSV-P could be ablated by rabbit antiserum to asialo-GM1, implicating NK cells in the in vivo rejection of these persistently infected tumors. These results suggest that NK cell recognition and killing of virus-infected cells in vivo and in vitro depend upon genetic contributions from both the virus and the host cell.

Animals↗
PubMed1992

Coxsackievirus B4 infection of the mouse pancreas: acute and persistent infection.

The course of infection of a pancreas-adapted isolate of coxsackievirus B4 was followed over a 10 month period in a murine model. Following intraperitoneal inoculation a typical acute infection was seen in nine of 10 inbred mouse strains. Virus rapidly infected the exocrine pancreas, titres peaking 3 to 4 days post-infection (p.i.). Lesions were almost exclusively confined to pancreatic acinar cells and varied in severity among the inbred strains. Virus shed into the blood-stream was not cell-associated. Evidence of persistent infection was found in nine mouse strains and infective virus was recovered from the pancreas of seven strains for up to 10 months p.i. Approximately 28% of pancreases examined beyond the acute phase showed focal inflammation and 22% showed focal necrosis (cell death). Virus was occasionally recovered from other organs (heart, liver and spleen), but lesions were rarely seen. Virus-specific antigen was localized to small groups of pancreatic acinar cells using an indirect immunogold silver staining technique. These observations suggested that the virus persists in pancreatic tissues because it seems unlikely that virus disseminated from distant sites would cause such localized infection. In three of these strains, the course of infection may have been influenced by superinfection with mouse hepatitis virus.

Acute Disease↗