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PubMed1985

[Significance of local tumor associated infiltration of mononuclear leukocytes for persistent tumor formations following transurethral resection (TUR) of bladder cancers].

In 140 patients with primarily curatively resected tumour of the urinary bladder the inclination to persistence was investigated in relation to the local peritumoural infiltration of leucocytes. 19% of the tumours with cellular infiltration and 33% of the tumours without cellular infiltration showed persistent tumour formations. Altogether 30 (21%) of the 140 tumours were persisting. The following parameters were found in persistent tumour formations: Multifocal tumours have a higher persistence rate than isolated primary tumours. With increasing degree of malignancy (G) the rate of persistence is elevating. It seems that in differentiated transurethral resection (separate resection of the exophyte, the tumour basis, resection of the marginal wall, if necessary, with second look operation) the local depth spreading of the tumour has no influence on the rate of persistence. Tumours without peritumoural infiltration with mononuclear leucocytes show a higher persistence rate than tumours with cellular infiltration, in which case this difference becomes even more significant with advanced tumour formation (T) and degree of malignancy (G).

Aged↗
PubMed1984

Complexity effects on reaction-time measures of visual persistence: evidence for peripheral and central contributions.

Two experiments are presented that attempt to determine the effect of operationally defined stimulus complexity on visual persistence. Two common measures of complexity are employed in both experiments. In Experiment 1, visual persistence for high-contrast, solid black figures increases with increasing target duration and with decreasing complexity. In Experiment 2, which uses outline figures of the same sizes and shapes as in the first experiment, visual persistence increases both with increasing target duration and with increasing complexity. It is proposed that the very different results from the two experiments may reflect the separate functioning of a visible, sensory persistence and a higher order, schematic persistence. The reaction-time (RT) measure of persistence that was employed may be sensitive to either of these persistences, depending upon stimulus and task conditions. Implications are suggested for (a) the importance of sensory processes in some manipulations of target complexity and (b) the possible role of peripheral and central factors in visual persistence.

Adult↗
PubMed1994

Expression of c-erb B-2 oncogene product in persistent gestational trophoblastic disease.

OBJECTIVE: Much debate exists on the initiation of chemotherapy for women at risk for persistent gestational trophoblastic disease. This is a result of a lack of early predictors for the development of persistent gestational trophoblastic disease after evacuation of a complete hydatidiform mole, because the only current reliable method of detection and diagnosis lies in persistent or rising postmolar beta-human chorionic gonadotropin values. We used immunocytochemical techniques to retrospectively study the expression of the c-erb B-2 oncogene product in formalin-fixed, paraffin-embedded trophoblastic tissues as a potential indicator of the development of persistent gestational trophoblastic disease. STUDY DESIGN: In this retrospective study 56 trophoblastic tumors were examined by means of immunocytochemical techniques to stain for the oncogene product for evidence of c-erb B-2 expression. Our 56 cases included original tissue from 20 cases of complete mole that progressed to persistent gestational trophoblastic disease, seven cases of choriocarcinoma after term pregnancy or abortion, and 29 cases of hydatidiform mole representing postevacuation, spontaneously regressing disease (including one partial mole). We also studied 11 cases of first-trimester trophoblast and 15 cases of term placenta as additional controls. RESULTS: Our results showed positive immunostaining for c-erb B-2 gene product in one case of persistent gestational trophoblastic disease, with negative staining in all other cases in the study groups and controls. CONCLUSION: Analysis for the significance of c-erb B-2 expression in persistent gestational trophoblastic disease showed that this correlation between c-erb B-2 expression and persistent gestational trophoblastic disease is not significant, suggesting that future efforts should be directed at the involvement of different oncoproteins.

Biomarkers, Tumor↗
PubMed1994

The induction of persistence of I-A expression by macrophages from Bcgr mice occurs via a protein kinase C-dependent pathway.

We have described conditions by which MHC class II (I-A) glycoproteins can be induced to be differentially expressed after treatment of macrophages with rIFN-gamma. Treatment of macrophages from BCG-resistant mice with 1 U of rIFN-gamma induced transient I-A expression that decayed in the presence of cycloheximide. Subsequent treatment of these macrophages with 100 U of rIFN-gamma induced the persistence of I-A that was not affected by cycloheximide. The aim of this investigation was to define, by pharmacologic intervention, the second signals that resulted in the induction of persistence of I-A. Treatment of the macrophages that transiently expressed I-A with PMA resulted in the induction of persistence. When we compared the effect of different protein kinase C (PKC) inhibitors with the induction of persistence by rIFN-gamma, we found that H-7 blocked the induction of persistence only when added before or at the same time as the addition of a high dose of rIFN-gamma. In contrast, the addition of staurosporine to macrophages as late as 2 h after treatment with high doses of rIFN-gamma inhibited the induction of I-A persistence. The addition of a high dose of rIFN-gamma to macrophages previously treated with a low dose of rIFN-gamma resulted in the synergistic activation of PKC. The effect of H-7 and of staurosporine on the activation of PKC activity coincided with the effect of these inhibitors on the induction of persistent I-A expression. Tyrosine kinase inhibitors genistein and herbimycin did not affect the induction of I-A persistence nor of PKC activation. Antibody to the IFN-gamma receptor inhibited PKC activation. Finally, the addition of the high dose of rIFN-gamma to macrophages from BALB/c.Bcgs mice, previously treated with the low dose of rIFN-gamma, failed to activate high levels of PKC activity attained after similar treatment of macrophages from BALB/c.Bcgr mice. One effect of the Bcg gene may be to regulate the activation of PKC activity.

Animals↗
PubMed1996

Persistent back pain and sciatica in the United States: patient characteristics.

Low back pain is an extremely common, seriously disabling, nonfatal public health problem worldwide. The National Low Back Pain Study was a multicenter study of a large, heterogeneous group of patients who have been referred to either a neurosurgeon or an orthopedic surgeon for the evaluation and treatment of a persistent complaint of low back pain. In this paper, we characterize persistent low back pain patients and their complaints, describe the impact of persistent low back pain on the patients' functional and psychological status, report on the patients' medical characteristics, and identify treatments that are currently prescribed for these patients. Persistent low back pain is most common among people in their mid-to-late thirties and early-to-mid forties. The patients are mostly white, well educated, and generally affluent. The majority are gainfully employed, but some quit working because of pain and those who do tend to be less educated, and more likely to be involved in litigation. The average patient has had low back pain intermittently for 10 years. The pain is usually well localized but its severity varies considerably. Besides pain, most persistent low back pain patients report a variety of motor and sensory deficits. Patients also report significant functional impairment at work, at play, and at home. The typical patient does not, however, display significant psychological distress. Most patients have consulted multiple health care providers, have received a variety of treatments, and have used a variety of medications to alleviate pain; a few have been subjected to more aggressive treatment measures including surgery, intradiscal therapy, and narcotic and psychoactive drugs. None of these treatments has been effective. Physical examinations of these patients do not provide significant clues for making a definitive diagnosis. Nonspecific abnormalities such as muscle spasm, tenderness, and trigger points are quite common, but motor weakness and sensory deficits in the lower extremities, and reflex changes in the knees and ankles, are much less common. The classic combination of reflex changes, motor weakness, and sensory deficits associated with specific protruded discs are extremely rare even though one of three patients had a diagnosis of disc herniation. Diagnostic imaging studies revealed that the majority of persistent low back pain patients have spondylotic abnormalities involving root compression or lumbar instability or both, with root compression as the primary cause of the complaint. Myofascial syndrome and lumbar instability were the next most common diagnoses. After a thorough evaluation by specialists in spinal disorders, three of five persistent low back pain patients were prescribed an additional course of conservative therapy, one of five was prescribed surgery, and the rest were prescribed no treatment. Persistent low back pain patients appear to be a distinct group of low back pain patients who are different from patients who have similar nonpersistent acute symptoms and those who have the chronic pain syndrome characterized by significant behavioral and psychological co-morbidities.

Adult↗
PubMed1997

Persistent diarrhoea in Nigerian children aged less than five years: a hospital-based study.

To identify possible risk factors for persistent diarrhoea, 307 children with acute diarrhoea presenting at the University College Hospital, Ibadan, Nigeria over a 10-month period from July 1993 to April 1994 were followed up prospectively until the resolution of the illness. The children were aged 6-60 months. In 36 (11.7%) of them, diarrhoea became persistent (i.e. lasted more than 14 days). This hospital frequency of 11.7% of persistent diarrhoea is, as expected, higher than the figures from previous community-based studies of diarrhoea from Nigeria. The major factor associated with persistent diarrhoea was poor nutritional status. Mean z scores of weight-for-height and weight-for-age were significantly lower in the persistent diarrhoea group, while mean z scores of height-for-age were similar in the two groups. The frequencies of occurrence of undernutrition, marasmus and kwashiorkor were also higher in the persistent diarrhoea group. Therefore, in common with studies from other regions of the world, malnutrition is an important risk factor for persistent diarrhoea in this group of Nigerian children. The implication of these findings is that reduction in the prevalence of malnutrition may be associated with reduction in the proportion of acute diarrhoeal episodes that eventually progress to persistent diarrhoea.

Acute Disease↗
PubMed1999

Persistence with treatment for hypertension in actual practice.

BACKGROUND: Despite the existence of efficacious medications, many patients in actual practice remain with uncontrolled hypertension. Randomized clinical trials, cannot address this issue well given their highly restricted environment. This paper examines persistence with antihypertensive therapy among patients in actual practice. METHODS: Cohort study of patients who received a diagnosis of hypertension and were treated between 1989 and 1994 identified through the Saskatchewan Health databases. Patients with concurrent diagnoses likely to affect initial treatment choice were excluded. The resulting population of 79,591 subjects was grouped into those with established hypertension (52,227 [66%]) and those with newly diagnosed hypertension (27,364 [34%]). The initial antihypertensive prescription, subsequent changes in treatment and persistence with antihypertensive therapy were analysed. RESULTS: Persistence with antihypertensive therapy decreased in the first 6 months after treatment was started and continued to decline over the next 4 years. Of the patients with newly diagnosed hypertension, only 78% persisted with therapy at the end of 1 year, as compared with 97% of the patients with established hypertension (p < 0.001). Among those with newly diagnosed hypertension, older patients were more likely than younger ones to persist, and women were more likely than men to persist (p < 0.001). INTERPRETATION: This analysis of actual practice data indicates that barriers to persistence occur early in the therapeutic course and that achieving successful therapy when treatment is started is important to maintaining long-term persistence.

Adult↗
PubMed1989

Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis. Macular Photocoagulation Study Group.

Persistence and recurrence of choroidal neovascularization after initial treatment with laser photocoagulation have been shown to be major contributors to loss of visual acuity. The 144 eyes assigned to krypton red laser photocoagulation in the Ocular Histoplasmosis Study-Krypton Laser were examined to describe persistence and recurrence in these patients. Persistent neovascularization was observed among 23% of treated patients and recurrent neovascularization was observed among an additional 8%. Both persistence and recurrence were accompanied by an increased frequency of severe visual loss. Patients with high blood pressure were more than 2.5 times as likely to have persistent neovascularization as patients without high blood pressure (95% confidence interval = 1.5, 4.8). Eyes in which the neovascular component of the complex was within 200 microns of the center of the foveal avascular zone were twice as likely to have persistent neovascularization (95% confidence interval = 1.2, 4.6). Eyes in which the treatment did not cover the neovascularization completely or did not meet the required level of intensity on the foveal side had a persistence rate approximately three times that of eyes in which the neovascularization was covered completely by intense, confluent burns (95% confidence interval = 1.7, 6.5). This last finding is of particular importance for ophthalmologists who treat similar patients.

Adult↗
PubMed1980

Impulsivity and persistence in adult inpatient "impulse" offenders.

Related cognitive tempo, self-report measures, and ratings of behavior to task persistence and persistence in treatment in adult inpatient/drug/alcohol/sex ("impulse") offenders (N = 43). Matching Familiar Figures test latencies and self-control scale scores were related to task persistance, but only the behavior ratings produced significant relationships with persistence in treatment. Although cognitively impulsive Ss were less task persistent than reflectives, impulsive and reflective Ss did not differ on self-reported locus of control and self-control, on the behavioral ratings, or on persistence in treatment. Behavioral ratings were most efficient for making predictions about persistence in treatment.

Adult↗
PubMed2002

How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis.

OBJECTIVE: To develop a clinical model for the prediction, at the first visit, of 3 forms of arthritis outcome: self-limiting, persistent nonerosive, and persistent erosive arthritis. METHODS: A standardized diagnostic evaluation was performed on 524 consecutive, newly referred patients with early arthritis. Potentially diagnostic determinants obtained at the first visit from the patient's history, physical examination, and blood and imaging testing were entered in a logistic regression analysis. Arthritis outcome was recorded at 2 years' followup. The discriminative ability of the model was expressed as a receiver operating characteristic (ROC) area under the curve (AUC). RESULTS: The developed prediction model consisted of 7 variables: symptom duration at first visit, morning stiffness for > or =1 hour, arthritis in > or =3 joints, bilateral compression pain in the metatarsophalangeal joints, rheumatoid factor positivity, anti-cyclic citrullinated peptide antibody positivity, and the presence of erosions (hands/feet). Application of the model to an individual patient resulted in 3 clinically relevant predictive values: one for self-limiting arthritis, one for persistent nonerosive arthritis, and one for persistent erosive arthritis. The ROC AUC of the model was 0.84 (SE 0.02) for discrimination between self-limiting and persistent arthritis, and 0.91 (SE 0.02) for discrimination between persistent nonerosive and persistent erosive arthritis, whereas the discriminative ability of the American College of Rheumatology 1987 classification criteria for rheumatoid arthritis was significantly lower, with ROC AUC values of 0.78 (SE 0.02) and 0.79 (SE 0.03), respectively. CONCLUSION: A clinical prediction model was developed with an excellent ability to discriminate, at the first visit, between 3 forms of arthritis outcome. Validation in other early arthritis clinics is necessary.

Adolescent↗
PubMed2002

Persistent ST-segment elevation after primary stenting for acute myocardial infarction: its relation to left ventricular recovery.

BACKGROUND: Early restoration of coronary artery patency in acute myocardial infarction (AMI) has been linked to improvement in survival. However, early recanalization of an occluded epicardial coronary artery by either thrombolytic agents or percutaneous transluminal coronary angioplasty (PTCA) does not necessarily lead to left ventricular (LV) function recovery. HYPOTHESIS: The aim of this study was to evaluate the relation between persistent ST elevation shortly after primary stenting for acute myocardial infarction (AMI) and LV recovery. METHODS: Thirty-one patients with primary stenting for AMI were prospectively enrolled. To evaluate the extent of microvascular injury, serial ST-segment analysis on a 12-lead electrocardiogram recording just before and at the end of the coronary intervention was performed. Persistent ST-segment elevation (Persistent Group, n = 11) was defined as > or = 50% of peak ST elevation and resolution (Resolution Group, n = 20) was defined as < 50% of peak ST elevation. Echocardiography was performed on Day 1 and 3 months after primary stenting. RESULTS: At 3 months, infarct zone wall-motion score index (WMSI, 2.1 +/- 0.6 vs. 2.7 +/- 0.3, p < 0.05) was smaller in the Resolution Group than in the Persistent Group, whereas wall motion recovery index (RI, 0.4 +/- 0.3 vs. 0.1 +/- 0.2, p < 0.05) and ejection fraction (58 +/- 5 vs. 43 +/- 10%, p < 0.05) were larger in the Resolution Group than in the Persistent Group. The extent of persistent ST elevation (% ST) shortly after successful recanalization of the infarct-related artery was significantly related to RI at 3 months (r = -0.4, p < 0.05). However, time to reperfusion was not related to RI at 3 months. There was also significant correlation between corrected TIMI frame count and %ST (r = 0.4, p < 0.05). CONCLUSIONS: Persistent ST-segment elevation shortly after successful recanalization (> or = 50% of the peak value), as a marker of impaired microvascular reperfusion, predicts poor LV recovery 3 months after primary stenting for AMI.

Aged↗
PubMed2004

Prevalence of persistent primary reflexes and motor problems in children with reading difficulties.

It has been shown that some children with reading difficulties have underlying developmental delay and that this may be related to the persistence of primary reflexes. This study investigated the prevalence of persistent primary reflexes in the ordinary primary school population and how this related to other cognitive and social factors. Three groups of 41 children were drawn from a representative, cross-sectional sample of 409 children (aged 9-10 years) attending 11 ordinary primary schools in N. Ireland. The three groups represented the bottom, middle and top 10% respectively of readers from the total sample population. The relative persistence (on a scale of 0 to 4) of the Asymmetrical Tonic Neck Reflex (ATNR) and the prevalence of motor difficulties were assessed for these 3 groups. The rôle of 5 predictor variables (verbal IQ, social deprivation, sex, month of birth and religious affiliation) in determining the reading level of the total sample was also investigated. It was found that the lowest reading group had a significantly higher mean level of ATNR (1.56 [95% CI 1.22-1.90]) compared with the middle reading group (0.56 [0.22-0.90]) and the top reading group (0.59 [0.25-0.92]). 17% of children in the lowest reading group had extremely high levels of the ATNR while 24% showed no presence of ATNR. This contrasted with 0% and 66%, respectively for both middle and top reading groups. It was also found that there was a significant difference between the lowest reading group and the top reading group on a standardised test of motor ability. Furthermore, there was evidence that ATNR persistence but not motor ability was associated with the sex of the child with boys, in particular, at risk. There was no evidence that ATNR persistence or motor ability was significantly associated with social deprivation. It was also found that there were no significant differences between dyslexic and non-dyslexic children with reading difficulties in motor (including balance) performance. This study highlights the high levels of primary reflex persistence in children with reading difficulties and it provides further evidence of the association between reading difficulties and movement difficulties in young children. However, while the implications for intervention are discussed, it is stressed that the persistence of primary reflexes cannot be used as a causal model for reading difficulties, including dyslexia.

Child↗
PubMed1996

Hepatitis B and C coinfections and persistent hepatitis B infections: clinical outcome and liver pathology after transplantation.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are common complications after orthotopic liver transplantation (OLT), but the liver pathology and clinical outcomes of HBV infection with HCV coinfection have not been thoroughly examined. In this study, we used the polymerase chain reaction (PCR) to detect HBV and HCV in pre- and post-OLT sera of 38 patients and correlated the findings with clinical outcome and liver pathology. Of 13 patients who were HBV and HCV negative before OLT, 9 acquired HBV infection, and 4 developed acquired HBV and HCV coinfections after OLT. Persistent HBV infections were present in 10 patients. Three patients with pre-OLT HBV infections developed persistent HBV and acquired HCV coinfections after OLT; 5 with pre-OLT HCV infections developed acquired HBV and persistent HCV coinfections after OLT, and 7 had persistent HBV and HCV coinfections before and after OLT. Portal/periportal inflammation was the same in all groups; however, lobular inflammation and fibrosis were more severe in patients with persistent HBV infections and in those with acquired HBV and HCV coinfections. Two major histopathological patterns were present in patients with HBV and HCV coinfections, one with predominant features of HCV infection, and the other with those of HBV infection. Patients with post-OLT HBV and HCV coinfections had survival rates similar to those with acquired HBV infection, whereas patients with persistent HBV infections experienced more allograft loss caused by chronic hepatitis or fibrosing cytolytic hepatitis, and had a more dire clinical outcome than the others. Although the limited numbers reported in this study prevent a definitive conclusion, our data suggest that in patients with HBV and HCV coinfections, the presence of HCV may improve the clinical outcome as compared with the expected outcome of persistent HBV infection alone.

Adult↗
PubMed2007

Changes of maternal transcripts in oocytes from persistent follicles in cattle.

A high incidence of early embryonic loss is associated with prolonged dominance of follicles. The objective of the present experiment was to determine if persistence of a follicle resulted in alterations in mRNA expression of important genes in the oocyte. Cows were assigned to four groups: growing follicles on day 6 (G0h) or day 8 (G48h) and persistent follicles on day 13 (P0h) or day 15 (P48h) of the estrous cycle (estrus = day 0). All cows were super-stimulated on day 1-4. Cows in G48h, P0h, and P48h groups received 25 mg prostaglandin (PG) F2alpha on day 6. Cows in P0h and P48h groups received progesterone from CIDR-B devices on day 5 through 13. Ovaries of cows in G0h, G48h, P0h, and P48h groups were removed on day 6, 8, 13, and 15, respectively. Oocytes were aspirated immediately after colpotomy and denuded of cumulus cells. Quantitative real-time PCR was used to measure the mRNA abundances of 10 selected genes important for early embryogenesis in oocytes obtained from growing and persistent follicles. Relative abundances of MSY2, PARN, and YY1 mRNA (P < 0.05) were significantly lower in oocytes from persistent than from growing follicles. Oocytes from persistent follicles, however, had greater abundances of PAP and eIF-4E transcripts (P < 0.05). The data indicate that persistence of a follicle leads to altered abundances of mRNA for genes important for regulation of transcription and protein translation in the oocyte, which could compromise development of early embryos in cows that ovulate a persistent follicle.

Animals↗
PubMed1998

One amino acid change on the capsid surface of poliovirus sabin 1 allows the establishment of persistent infections in HEp-2c cell cultures.

Poliovirus mutants (PVpi) selected during the persistent infection of human neuroblastoma cells can establish secondary persistent infections in nonneural HEp-2c cells (I. Pelletier, T. Couderc, S. Borzakian, E. Wyckoff, R. Crainic, E. Ehrenfeld, and F. Colbère-Garapin, 1991, Virology, 180, 729-737). Previous results from our laboratory have also shown that, in the genome of PVpi S11 derived from the Sabin 1 strain, the genomic region involved in this phenotype contains 11 missense mutations which map exclusively to the genes encoding the capsid proteins VP1 and VP2. We report here the identification of precise viral determinants able to confer the capacity to establish persistent infections in HEp-2c cell cultures to the lytic Sabin 1 strain. We used a strategy based on the observation that PVpi, after a few months of persistent infection in HEp-2c cells, tend to regain a more lytic phenotype in uninfected HEp-2c cell cultures. We constructed mutant viruses carrying only a few mutations potentially involved in the phenotype of persistence. Two mutations were identified, one corresponding to the substitution His>Tyr of amino acid 142 of VP2 and another corresponding to the substitution Val>Ile of amino acid 160 of VP1. Mutants carrying one or the other of the two determinants established persistent infections in HEp-2c cell cultures in about 20% of the infections. Higher frequencies were obtained with the mutant carrying both determinants (30%), and with PVpi S11 (63%), indicating that the effects of several determinants can be cumulative. The two determinants are localized on the capsid surface in a region known to be involved in the interactions between poliovirus and its cell receptor and in fact, we demonstrate here that in the case of the two persistent mutants, these interactions are modified.

Amino Acid Substitution↗
PubMed1998

Two amino acid substitutions in the type 3 poliovirus capsid contribute to the establishment of persistent infection in HEp-2c cells by modifying virus-receptor interactions.

After 2.5 months of persistent infection in human neuroblastoma cells by the type 3 poliovirus (PV3) wild-type Leon strain, a mutant (PVpi), L2-2, capable of establishing a persistent infection in nonneural HEp-2c cells was isolated. Sequence analysis of the viral capsid protein genes revealed the presence of seven missense mutations, three of which were also present in a second PVpi, suggesting that they could be important determinants of the persistent phenotype. When the three mutations were introduced into the lytic Leon strain separately, in pairs or all together, all but one of the viruses was capable of establishing a persistent infection. However, aside from the triple mutant, only one mutant virus, bearing a Leu at position VP213 in the capsid interior and an Asn at position VP1290 on the capsid surface, was capable of establishing persistent infections in more than 30% of the cultures. When present together, these two determinants affect the early steps of the virus cycle including cell binding and the receptor-mediated conformational changes believed to be necessary for viral penetration and uncoating. In fact, this persistent double mutant appears to undergo a novel capsid transition when in contact with the human PV receptor, altering from the native virion which sediments at 160S to a form which sediments at about 147S. We propose that this modification could be the mechanism by which PV3 is able to establish persistent infections in HEp-2c cell cultures.

Amino Acid Substitution↗
PubMed1998

Variability of persisting MHV RNA sequences constituting immune and replication-relevant domains.

Survivors of acute infection with the neurotropic JHM strain of mouse hepatitis virus develop a persistent infection of the central nervous system associated with chronic ongoing demyelination. Persistence is characterized by viral RNA in the absence of infectious virus. To associate persistence with possible immune evasion and/or replication defects, viral RNA from brains of acutely and persistently infected mice was examined for mutations by reverse transcriptase-PCR. Sequences analyzed included the encapsidation sequence (ECS), the transmembrane domains of the matrix (M) protein, and a cytotoxic T cell (CTL) epitope within the nucleocapsid (N) protein. The ECS, present only on genomic RNA, revealed minimal variability and was detected out to 120 days postinfection, suggesting low levels of replication. The M gene sequence also remained stable during persistence despite random mutations during the acute phase. Although the N gene sequence exhibited the greatest diversity, mutations were random and not selected for during persistence. A single exception was detected comprising a prominent Pro to Ser substitution in a region of N not associated with any known regulatory or immune function. Of the N gene mutations found within the CTL epitope in responder mice (H-2d), one resulted in reduced CTL recognition with no evidence of antagonist activity. However, this mutation was also detected in nonresponder mice (H-2b), suggesting that escape variants arising from CTL pressure play no role in establishing persistence in immunocompetent hosts infected as adults.

Animals↗
PubMed2000

Expression of mutated poliovirus receptors in human neuroblastoma cells persistently infected with poliovirus.

Poliovirus (PV) is able to establish persistent infections in human neuroblastoma IMR-32 cells [Colbère-Garapin et al. (1989) Proc. Natl. Acad. Sci. USA 86, 7590]. During persistent infection, PV mutants are selected that display substitutions of residues in regions of the capsid known to interact with the PV receptor (PVR), a glycoprotein of the immunoglobulin superfamily. The mechanism of persistent infection in IMR-32 cells may therefore involve the selection of mutant PVRs. To test this hypothesis, the sequences of the PVR mRNAs in uninfected IMR-32 cells and in two independent IMR-32 cell cultures persistently infected with the Mahoney strain of PV type 1 (PV1/Mahoney) were determined. The PVR mRNA population of uninfected cells was homogeneous, and no mutation was repeatedly found, whereas that of persistently infected cells displayed missense mutations. Particular mutations were repeatedly detected, and all of them mapped to the N-terminal domain of PVR (domain 1), which interacts directly with PV. These mutations generated several types of PVR variants with the following substitutions: Ala67-->Thr alone, Ala67-->Thr associated with Gly39-->Ser, and Arg104-->Gln. Functional analysis of PVR in murine LM cells, stably expressing each of the PVR forms, showed that the PVR forms selected during persistent infection conferred on LM cells partial resistance to PV1/Mahoney-induced lysis. Although adsorption onto PVR seemed to be independent of the PVR form, an analysis of the conformational changes of the capsid during the early steps of the PV cycle provided evidence that the Ser39/Thr67 and Gln104 substitutions almost halved the conversion of 160S infectious particles into 135S A particles associated with the PV-PVR interaction. Altogether, these findings indicate that during persistent infection, specific mutations were selected in the domain 1 of PVR and that these mutations increased the resistance of cells to PV-induced lysis. These results are discussed in view of the position of the mutations on PVR.

Amino Acid Substitution↗