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At least 19 recordsLinked to original sources
PubMed1966

Persistent infection of cells in culture by measles virus. II. Effect of measles antibody on persistently infected HeLa sublines and recovery of a HeLa clonal line persistently infected with incomplete virus.

Rustigian, Robert (Tufts University School of Medicine, Boston, Mass.). Persistent infection of cells in culture by measles virus. II. Effect of measles antibody on persistently infected HeLa clonal line persistently infected with incomplete virus. J. Bacteriol. 92:1805-1811. 1966.-The effect of viral antibody on persistent infection of HeLa cells by the Edmonston strain of measles virus was investigated by culturing cells from three persistently infected clones in medium supplemented with human immune globulin. The three infected HeLa clones were isolated from a persistently infected parent line. Two sublines which were grown in the presence of measles antibody developed a nonyielder state, wherein there is no detectable virus infectious for normal HeLa cultures. There is, however, continued synthesis of intracellular viral antigen and formation of viral intracytoplasmic inclusion bodies. The development of a nonyielder state was associated with a marked decrease in the degree of hemadsorption in cultures of both sublines. Further studies of the viral properties of non-yielder HeLa cell populations were made with a clone obtained from one of these sublines by plating under antibody. Persistent infection in this line was characterized by synthesis of incomplete virus even when the cells were cultured thereafter in anti-body-free medium. This was evidenced by (i) failure to recover infectious virus from the clonal population despite continued formation of intracellular viral antigen and viral intracytoplasmic inclusion bodies in a majority of the cells, (ii) the presence of only a few cells with surface viral antigen(s) including hemagglutinin, and (iii) the relatively weak antibody response to viral envelope antigen(s) after injection of cells into guinea pigs.

Animals↗
PubMed1973

Selection of temperature-sensitive mutants during persistent infection: role in maintenance of persistent Newcastle disease virus infections of L cells.

Virus mutants (NDV(pi)) recovered from L cells persistently infected with Newcastle disease virus (NDV, Herts strain) are temperature-sensitive (ts) at 43 C, although the wild-type virus (NDV(o)) which initiated the persistent infection replicates normally at that temperature. To study the relationship between the ts marker of NDV(pi) and the other properties which distinguish this virus from NDV(o), NDV(pi) ts(+) revertants were selected at the nonpermissive temperature and NDV(o) ts mutants were generated by treating NDV(o) with nitrous acid. Spontaneously-occurring ts mutants in the Herts NDV population were also isolated. The different virus populations were characterized with regard to plaque size, virulence for eggs, and thermal stability of infectivity, hemagglutinin, and neuraminidase. The NDV(pi) ts(+) revertants, although no longer temperature-sensitive, retained NDV(pi) properties, whereas both spontaneously-occurring and mutagen-induced ts mutants remained wild-type in their other properties. These findings showed that the properties which characterized NDV(pi) were independent of the ts marker. However, the ts marker and the other markers of NDV(pi) were coselected during the persistent infection, and the combination of those markers appeared to be important in the outcome of NDV infection of L cells. NDV(pi) replicated productively in L cells, whereas NDV(o), the NDV(pi) ts(+) revertants, and the spontaneously-occurring ts mutants all yielded covert infections in L cells. The role of the selection of ts mutants in persistent infection was confirmed as follows: L cells were persistently infected with NDV(pi) ts(+) revertants and NDV(o) ts mutants. Virus recovered from the persistently infected cultures after eight cell passages was always temperature-sensitive and of smaller plaque size than the parental virus in chicken embryo cell cultures. Similar results were obtained with virus recovered from L-cell cultures persistently infected with two other velogenic strains of NDV, the Texas-GB and Kansas-Man strains. These results strongly suggest that selection of ts mutants during the persistent infection was not random and played a role in establishment or maintenance of the persistent infection, or both.

Animals↗
PubMed1987

Immediate persistent infection by human parainfluenza virus 3: unique fusion properties of the persistently infected cells.

We describe here a persistently infected cell system with unique properties. Cells infected with human parainfluenza virus type 3 (PF3) at high multiplicities of infection showed little or no cytopathic effects (cell fusion). Unlike other paramyxovirus persistent infections that require a long development time, the majority of the cells survived the initial infection and formed persistently infected cell cultures that were immediately available for study. In addition, unlike other paramyxovirus persistent infections, the PF3 system described here produced high levels of infectious virus and did not undergo periodic crises. Although cells persistently infected with PF3 contained large amounts of the cleaved, active form of the viral fusion protein, F1, the persistently infected cells did not fuse with each other. However, they did fuse with uninfected cells within minutes of cell-to-cell contact. Other persistent paramyxovirus infections do not have this property. Fusion occurred with all cells tested, including red blood cells, and was not dependent on protein synthesis. The unique fusion properties of these PF3 persistently infected cells make this an interesting system for the study of mechanisms of viral fusion and mechanisms of inhibition of viral fusion.

Animals↗
PubMed2026

The Conundrum of Shiga Toxin-Producing Escherichia coli O157:H7 Persistence: Evidence for Locally Persistent Lineages.

Evidence suggests that Shiga toxin-producing Escherichia coli (STEC) strains do not persist at the farm level. We hypothesized that ecosystem-level STEC persistence occurs and contributes significantly to disease burden. We tested this by identifying locally persistent lineages (LPLs) of STEC O157:H7 in Minnesota. We identified 15 distinct LPLs, which were associated with 35.3% of reported cases in Minnesota and persisted for 1.3-8.6 years. Locally persistent lineages were associated with multiple outbreaks with Minnesota sources and no multi-state outbreaks, and LPL cases were spatially clustered. Our findings show long-term persistence in defined geographic areas, suggesting the importance of ecosystem-level persistence.

Minnesota↗
PubMed1966

Persistent infection of cells in culture by measles virus. I. Development and characteristics of HeLa sublines persistently infected with complete virus.

Rustigian, Robert (Tufts University School of Medicine, Boston, Mass.). Persistent infection of cells in culture by measles virus. I. Development and characteristics of HeLa sublines persistently infected with complete virus. J. Bacteriol. 92:1792-1804. 1966.-After the development of marked cytopathic effects in HeLa cultures infected with the Edmonston strain of measles virus, renewed cell growth occurred, and HeLa sublines persistently infected with measles virus were obtained. Persistent infection has occurred in a large fraction of the cells of infected clonal lines for more than 300 to 500 cell generations during a period of 6 years. One mechanism by means of which infection was maintained in the clonal lines is transmission of virus or viral subunits from cell to cell at division. Continued subculture of the persistently infected populations resulted in the virtual disappearance of cytopathic effects, a marked decrease in the amount of extracellular virus, and alterations in the cytopathogenicity of virus recovered from persistently infected populations. The intracellular virus-host cell events in late passages of the infected clonal lines appeared to be similar to those in cells of primary infected cultures at early stages of infection, as judged by the pattern of viral immunofluorescence and the very low incidence of cells with intranuclear inclusion bodies. Cultures of the persistently infected clonal lines were highly resistant to super infection by parent Edmonston virus. Cultures of one of these clonal lines were just as susceptible as normal HeLa cultures to vaccinia, herpes simplex, and polio type 2 viruses, and a simian agent, with a possible low degree of resistance to the simian agent.

Antigens↗
PubMed1990

Persist or quit? Testing for a genetic contribution to smoking persistence.

We consider three alternative parametric models to describe genetic and environmental influences on smoking initiation and smoking persistence. Under the single liability dimension model, the same genetic and environmental influences which determine smoking initiation also influence smoking persistence. Under the independent liability dimensions model, independent initiation and persistence dimensions determine onset of smoking, and persistence in those who become smokers. The combined model also postulates separate initiation and persistence dimensions, but allows for the possibility that some smokers are so low on liability to smoke on the initiation dimension that they become ex-smokers for this reason. Reanalysis of London twin data published by Eaves and Eysenck support the single liability dimension model. We discuss the difficulty of reconciling this finding with the hypothesis that nicotine dependence is a major determinant of smoking persistence, but caution that sample sizes in the London twin study were small.

Diseases in Twins↗
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↗
PubMed1992

Measles virus from a long-term persistently infected human T lymphoblastoid cell line, in contrast to the cytocidal parental virus, establishes an immediate persistence in the original cell line.

To investigate the mechanisms of measles virus (MV) establishment and maintenance of persistence in lymphoid cells, we have established a long-term persistent infection with MV, Edmonston strain, in the human T lymphoblastoid cell line MOLT4, which has been in continuous culture for over 8 years. In this culture, designated MOMP1, more than 98% of cells display viral antigens. The MOMP1 culture is immune to superinfection with MV and is not cured by anti-MV antibodies. No evidence of defective interfering particles was obtained. The persistently infected culture releases an infectious virus showing a miniplaque and thermoresistant modified phenotype that, unlike the parental virus Edmonston strain which produces a lytic infection with extensive cell fusion, establishes an immediate persistence in MOLT4 cells with neither significant loss of cell viability nor cell fusion. This suggests that the modification in the virus suffices to maintain the state of persistence without requiring a coevolution of the host cell during the infection, as has been reported in other persistent virus infections.

Antibodies, Viral↗
PubMed1986

Persistent elevation of the aminoterminal peptide of procollagen type III in serum of patients with acute viral hepatitis distinguishes chronic active hepatitis from resolving or chronic persistent hepatitis.

We measured the serum concentration of the aminoterminal propeptide of collagen type III (PIIIP) in 22 patients with acute viral hepatitis (19 hepatitis B, 3 hepatitis non-A, non-B). Nine patients showed persistent biochemical remission, 13 patients developed chronic active hepatitis (CAH); 6 of those underwent therapy with methylprednisolone and azathioprine. Thirteen patients with chronic persistent viral hepatitis (CPH) and 38 healthy individuals were also investigated. In the control group, PIIIP values were 9.5 +/- 2.25 ng/ml (chi +/- SD; range 4-14 ng/ml). All patients with acute hepatitis showed elevated PIIIP values (range 20-125 ng/ml). In the 9 patients with biochemical resolution, PIIIP normalized after a maximum of 6.5 months (range 7.5-14 ng/ml). In CAH, PIIIP was persistently elevated on the day of the diagnostic biopsy (range 15.6-35.7 ng/ml). In comparison, the patients with chronic persistent hepatitis showed a range of 5.0-15.4 ng/ml. Differences between controls and CAH and CPH/CAH were statistically highly significant (P less than 0.001). Treatment of patients with CAH by immunosuppression resulted in normal PIIIP values in 3 and persistently elevated values in 3. One additional patient had normal PIIIP after treatment with an increased dose of methylprednisolone of 16 mg p.d. Serum concentrations of PIIIP offer a non-invasive index for the development of chronic active hepatitis from acute viral hepatitis. This blood test may also be useful for monitoring immunosuppressive treatment in CAH.

Acute Disease↗
PubMed1976

Ontogeny of persistence: immediate and long-term persistence in rats varying in training age between 17 and 65 days.

In Experiment 1, six age groups of rats were trained to run an alley for either partial (PRF) or continuous reinforcement (CRF). Training was during a 2-day period starting at six different ages, and extinction was initiated about 12 hr later. There was a clear partial reinforcement extinction effect (PREE) at all ages and, particularly after PRF training, an inverse relationship between resistance to extinction and age. In Experiment 2, retention and durability of persistence as well as immediate persistence were tested following acquisition at three different ages. The immediate extinction tests confirmed the results of Experiment 1. In the delayed extinction tests, greater resistance to extinction following PRF than following CRF was found in all age groups after both the retention and durability manipulations. In neither test was there an effect of age in original acquisition on the magnitude of adult persistence. These experiments confirm earlier findings of remarkable persistence in rats trained and tested at weanling age, show that the persistence is even greater in pre-weanlings, and show that it is retained into young adulthood.

Age Factors↗
PubMed1988

Coping with persistent pain: a comparison of persistent pain sufferers in a specialty pain clinic and in a family practice clinic.

Coping has been defined as an effort to manage external and internal demands and conflicts that tax or exceed a person's resources. This paper examines the types of coping strategies used by two groups of persistent pain sufferers: one from a family practice clinic and the other from a specialty pain clinic. The relationship between the use of different types of coping strategies and adjustment was determined. The two study groups of persistent pain sufferers differed significantly from each other on many of the indices developed to tap adjustment but did not differ on any of the Billings and Moos original categories of coping strategies. When a factor analysis of coping items was performed, 5 valid clusters relevant to the chronic pain patient samples were determined. The factor the authors entitled 'adversarialness' with the qualities of dysphoric withdrawal, avoidant behavior and catastrophizing was found to explain adjustment defined by several indices. The authors conclude that it may be important to help persistent pain sufferers to alter their attitudes and behavior that tend toward catastrophizing, avoidance and withdrawal, rather than simply concentrate on trying to teach them techniques for 'coping with stress.'

Adaptation, Psychological↗
PubMed1991

Transmission of viral persistence by transfection of human cultured cells with RNA of a persistent strain of echovirus 6.

A cloned line of persistently infected (PI) human cells has been established with a strain of the normally lytic, echovirus 6. All of the cells contained non-lytic viral RNA and synthesized defective viral particles. The present study was undertaken to determine whether replication of non-lytic viral RNA occurred after transfection. Uninfected human WISH cells were transfected with viral RNA recovered either directly from persistently infected PI cells or from virus particles produced by PI cells. Cytoplasmic extracts were prepared at various times after transfection and examined for presence of viral RNA and protein. The viral RNA was detected by hybridization of Northern blots of cellular RNA extracts with a cDNA clone of wild-type, lytic echovirus 6. Viral proteins were isolated by immunoprecipitation with specific anti-viral serum and analysed by polyacrylamide gel electrophoresis. Increased concentrations of viral RNA were detectable in cellular extracts at 48 h after transfection. Replicate transfected cultures retained viral RNA and produced viral proteins after cultivation for 287 days. RNA extracts from the transfected cells did not produce cytopathology or lytic virus. Thus, conversion of uninfected cells into a persistently infected cell line was accomplished by transfection with the non-lytic genome of echovirus 6.

Blotting, Northern↗
PubMed1990

Genetic basis of viral persistence: single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice.

This study has identified a single amino acid change in the viral glycoprotein that profoundly affects the ability of lymphocytic choriomeningitis virus (LCMV) to persist in its natural host. Adult immunocompetent mice infected with a variant of the Armstrong strain, spleen isolate clone 13 (svA/svA), harbor virus for several months and exhibit suppressed T cell responses. In contrast, adult mice infected with a reassortant virus (svA/wtA) that contains the L segment of the spleen variant and the S segment of the parental wt Armstrong, make potent LCMV-specific CTL responses and clear the infection within 2-4 wk. These two viruses, spleen variant clone 13 and the reassortant svA/wtA, are identical in their noncoding regions and show no amino acid changes in any of their viral genes except for one substitution in the glycoprotein. The reassortant virus svA/wtA has a phenylalanine at amino acid residue 260 of the glycoprotein, whereas the spleen variant clone 13 has a leucine at this position. This study constitutes one of the first reports defining the genetic basis of viral persistence at the whole animal level, and identifying a single mutation that markedly increases the ability of a virus to persist in its natural host.

Amino Acid Sequence↗
PubMed1989

Induction of persistent diestrus followed by persistent estrus is indicative of delayed maturation of tonic gonadotropin-releasing systems in rats.

The relationship between the amount and duration of administration of estradiol benzoate (EB) to newborn female rats and the induction of sterility was examined in 407 animals. Vaginal smear patterns were classified into 3 types according to the incidence of vaginal proestrus and estrus over a 10-day period: persistent estrous (PE), persistent diestrus (PD), and intermediate (INT), so that the changes in vaginal smear patterns could be analyzed quantitatively. Incidence of the PE pattern was most frequent in the rats that received a single injection of 10 micrograms EB on the day of birth (Day 1). Almost all of the animals receiving 10 daily injections of 10 micrograms EB from Day 1 showed persistent diestrus until at least 100 days of age. In the rats that were given 5 daily injections of 10 micrograms EB Day 1 through Day 5, or a single injection of 100 micrograms EB on Day 3, the incidence of the PD pattern was high at 41-60 days of age, but later the PD-type was replaced by the PE pattern of vaginal smears. In the rats that were treated with 5 daily injections of 10 micrograms EB from Day 1 through Day 5 and were ovariectomized on Day 22, a slight but significant increase in the level of luteinizing hormone in plasma was noted after administration of EB and progesterone on Day 100 but not on Day 50. These results indicated that neonatal injections of EB induce sterility, but the effect is dependent on the amount of EB injected and length of time over which the injections are given.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1987

Persistence of serum hepatitis B virus deoxyribonucleic acid in hepatitis B surface antigen-positive patients with chronic persistent hepatitis treated with prednisone.

The effect of a short course of prednisone therapy was evaluated in 8 patients with liver biopsy-verified chronic persistent hepatitis B. In 6 of the 8 (75%) patients, an abrupt fall in serum alanine aminotransferase levels after the initiation of prednisone was noted, and in 4 patients, there was an increase in serum alanine aminotransferase values after prednisone was discontinued. However, the serum levels of hepatitis B virus deoxyribonucleic acid were consistently greater than or equal to 200 pg before, during, and after the course of treatment in 7 of the 8 (87.5%) patients. All patients were initially hepatitis B e antigen-positive and remained so during the study period. These findings indicate that, unlike some patients with chronic active hepatitis B, immunosuppression with prednisone had no effect in altering hepatitis B viral replication in patients with chronic persistent hepatitis.

Adult↗
PubMed1989

Serum antibodies to giardial surface antigens: lower titres in persistent than in non-persistent giardiasis.

Antisera to two antigens of Giardia lamblia--plasma membrane (PM) protein and an affinity-purified surface antigen (SA56)--were raised in rabbits, and shown to agglutinate and kill trophozoites in vitro. These antibodies were also demonstrated by ELISA in the sera of paediatric patients with giardiasis. The titres of both antibodies were significantly higher in non-persistent (acute) and asymptomatic cases than in patients with persistent infection; and the latter group did not respond to anti-giardial therapy. The inability of this group to clear G. lamblia infection, in spite of therapy, may result from the low level of antibodies which mediate the killing of trophozoites.

Animals↗
PubMed1991

Molecular basis of viral persistence: a single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with suppression of the antiviral cytotoxic T-lymphocyte response and establishment of persistence.

Isolates of lymphocytic choriomeningitis virus (LCMV) that elicit a cytotoxic T-lymphocyte response (CTL+) have been compared with isolates that suppress the CTL response (CTL-) in an effort to map this phenotype. A single amino acid change in the glycoprotein of the LCMV Armstrong (ARM) strain is consistently associated with the CTL- trait and the ability of the virus to persist (P+). The CTL+ P- parental strain spontaneously gives rise to CTL- P+ variants within lymphoid tissues of mice persistently infected from birth. To map the structural basis of the phenotype, the complete RNA sequence of LCMV ARM 53b (CTL+) was compared with that of its variant ARM clone 13 (CTL-). Differences in 5 of 10,600 nucleotides were found. Three changes are noted in the large L RNA segment, and two are noted in the small S RNA segment. Only two of the changes distinguishing CTL+ from CTL- isolates affect amino acid coding: lysine to glutamine at amino acid 1079 of the polymerase protein, and phenylalanine to leucine at amino acid 260 of the envelope glycoprotein (GP). We also analyzed two additional CTL- variants and four spontaneous CTL+ revertants. All three CTL- variants differ from the original CTL+ parental strain at GP amino acid 260, indicating that this amino acid change is consistently associated with the CTL- phenotype. By contrast the other four mutations in LCMV are not associated with the CTL- phenotype. Sequence analysis of the coding regions of four CTL+ revertants of ARM clone 13 did not reveal back mutations at the GP 260 locus. This finding indicates that the GP 260 mutation is necessary but not sufficient for a CTL- P+ phenotype and that the reversion to CTL+ P- is likely either due to secondary mutations in other regions of the viral genome or to quasispecies within the revertant population that make significant contributions to the phenotype.

Amino Acid Sequence↗
PubMed1988

Changes in uterine estrogen receptor concentrations in persistent estrous and persistent diestrous rats.

Changes in uterine weight and the estrogen receptor concentrations were examined in persistent estrous (PE) and persistent diestrous (PD) rats at 80 days of age. To prepare PE rats, 100 micrograms estradiol benzoate (EB) was injected sc into 3-day-old females. PD rats were obtained by daily injections of 10 micrograms EB into females for 10 consecutive days from the day of birth. The uterine weight in PE rats at 80 days was comparable to that in metestrous controls. The uteri of PD rats were smaller than those in PE rats. The concentrations of estrogen receptor in nuclear fractions in PE and PD rats were much lower than those in proestrous controls. Receptor concentrations in cytosol fractions were significantly lower in PE and PD rats than in control diestrous, proestrous and estrous rats. The dissociation constants and sedimentation coefficients of estrogen receptors in PE and PD rats were found to be in the same range as those in control rats. Thus, the reduction in the activity of cytosol receptors in these rats is attributable to a quantitative change in the amount of estrogen receptor protein. To study the response of the uterus to estrogen, ovariectomized rats were injected daily with 10 micrograms estradiol for 7 consecutive days. The uterine growth of PE and PD rats after administration of estradiol was less marked than in controls, indicating a reduction of estrogen sensitivity of the uterus. Seven daily administrations of estradiol continued to increase the concentration of uterine cytosol estrogen receptor in controls. In contrast, in PE and PD rats, the receptor concentrations continued to increase during the first 3 days, and then remained constant. These data suggest that EB in neonatal treatment may directly affect the mechanism of receptor synthesis in uterine tissues. This effect may contribute to the reduction of the uterine response to estrogen.

Animals↗