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PubMed2005

Virus perpetuation in populations: biological variables that determine persistence or eradication.

In this review, I use the term "perpetuation" for persistence of a virus in a population, since this is a different phenomenon from persistence of a virus in an infected host. Important variables that influence perpetuation differ in small (<1000 individuals) and large (>10,000) populations: in small populations, two important variables are persistence in individuals, and turnover of the population, while in large populations important variables are transmissibility, generation time, and seasonality. In small populations, viruses such as poliovirus that cause acute infections cannot readily be perpetuated, in contrast to viruses such as hepatitis B virus, that cause persistent infections. However, small animal populations can turnover significantly each year, permitting the perpetuation of some viruses that cause acute infections. Large populations of humans are necessary for the perpetuation of acute viruses; for instance, measles required a population of 500,000 for perpetuation in the pre-measles vaccine era. Furthermore, if an acute virus, such as poliovirus, exhibits marked seasonality in large populations, then it may disappear during the seasonal trough, even in the presence of a large number of susceptible persons. Eradication is the converse of perpetuation and can be used as a definitive approach to the control of a viral disease, as in the instance of smallpox. Therefore, the requirements for perpetuation have significant implications for practical public health goals.

Animals↗
PubMed1995

Exogenous GABA persistently opens Cl- channels in cultured embryonic rat thalamic neurons.

We recorded whole-cell Cl- currents in cultured embryonic rat thalamic neurons by brief applications of GABA or the structural analogue muscimol. In 17 of 141 neurons (12%) the Cl- current persisted for a minute or more after the pipette was removed from the bath. Cl- current never persisted after muscimol exposure even in those cells exhibiting persistent GABA-activated currents (PGC). The half decay times (T50) of PGCs were exponentially and asymptotically related to the duration of GABA exposure and could be interrupted or completely aborted by low-pressure application of saline. PGCs were insensitive to membrane potential, to Tiagabine, a nipecotic acid analogue known to block GABA uptake, and persisted in Cao(2+)-free medium. Fluctuation analysis revealed that PGCs exhibited inferred Cl- channel properties whose kinetic components and estimated average elementary conductance showed no significant difference from those estimated during GABA exposure. The relative contribution of low frequency components was consistently reduced and that of high frequency components modestly increased during PGC compared to those recorded during GABA exposure. Taken together, the results suggest the existence of a superficial compartment in these embryonic neurons that can momentarily accumulate and release exogenous GABA.

Animals↗
PubMed1986

Persistence in population models with demographic fluctuations.

A persistence and extinction theory is developed through analytical studies of deterministic population models. Under hypotheses that require demographic parameters to fluctuate temporally, the populations may or may not oscillate. Extinction, when it occurs, is asymptotic. An hierarchy of persistence criteria, based upon fluctuations measured by time average means, is derived. In some situations a threshold value is found to separate persistent population models from those that tend to extinction. Application of the persistence-extinction theory is to the problem of assessing effects of a toxic substance on a population when toxicant inputs to the environment and to resources are oscillatory.

Demography↗
PubMed1987

Prevalence and causes of microscopic haematuria in type 1 (insulin-dependent) diabetic patients with persistent proteinuria.

The prevalence and causes of microscopic haematuria were examined in all Type 1 (insulin-dependent) diabetic patients with persistent proteinuria (diabetes duration greater than or equal to 5 years) attending the outpatient clinic at Hvidöre Hospital during 1985. One hundred eighty-four patients (69F/115M) out of 1024 Type 1 patients had persistent proteinuria (18%). Microscopic haematuria was defined as greater than or equal to 3 erythrocytes per high power field in two or more sterile urine samples. Twenty-three Type 1 patients with persistent proteinuria (7F/16M, aged 35.4 +/- 13 years) had microscopic haematuria (12.5%). No significant changes were found between the group with and without microscopic haematuria: blood pressure 148/89 +/- 22/11 versus 145/91 +/- 20/11 mmHg, duration of diabetes when persistent albuminuria occurred 17 +/- 8 versus 20 +/- 10 years, serum creatinine 99 +/- 24 versus 98 +/- 31 mumol/l, simplex retinopathy 61 versus 54%, proliferative retinopathy 39 versus 42%, and no signs of retinopathy 0 versus 4%. Kidney biopsy was performed in 13 out of the 23 patients with microscopic haematuria. Diabetic glomerulosclerosis was present in all 13 patients, but 9 patients had a non-diabetic renal disease superimposed (mesangioproliferative glomerulonephritis (n = 5), membranous glomerulonephritis (n = 3) and sarcoidosis (n = 1). Microscopic haematuria is a rare finding, frequently reflecting superimposed non-diabetic glomerulopathies, in Type 1 diabetic patients with diabetic nephropathy and well preserved kidney function.

Adolescent↗
PubMed1995

Studies on canine distemper virus persistence in the central nervous system.

Chronic progressive demyelination in canine distemper virus (CDV) infection is associated with persistence of the virus in the nervous system. We studied persistence by examining expression of CDV mRNA corresponding to all genes of the virus as well as genomic CDV RNA in brain sections of dogs with acute and chronic demyelinating disease. All virus mRNAs were expressed in acute demyelinating lesions in a way similar to that seen in lymphoid tissues, the primary replication site of CDV. Their distribution corresponded very well with immunohistochemical detection of virus protein. In contrast, much more CDV mRNA than virus protein was found in gray matter areas suggesting that translation of CDV can be impaired in nervous distemper. Virus protein and RNA were cleared from chronic inflammatory demyelinating lesions. mRNA corresponding to the distal genes (F; H; L) of CDV disappeared first in inflammatory lesions for technical reasons associated with the particular mode of transcription of morbilliviruses. CDV RNA and protein persisted in chronically ill dogs in other areas of the CNS in which inflammation had not occurred. Our results suggest that persistence of CDV is favored by non-cytolytic spread of the virus and restricted infection of certain cells with reduced viral protein expression. Both tend to delay immune recognition of the virus.

Animals↗
PubMed1988

Non-persisting early foci of altered hepatocytes induced in rats by N-nitrosomorpholine.

Male Sprague-Dawley rats were treated for 7 weeks with 120 mg/l N-nitrosomorpholine in their drinking water. At the end of the treatment period there were large numbers of enzyme-altered foci in the liver. During the following 10 weeks, the number of foci decreased significantly. This decrease in the number of enzyme-altered foci was due to the disappearance of a special type of focus. The typical features of these non-persisting foci were distinct enzyme histochemical and striking morphological alterations as well as the localization in or close to the third zone, as defined by Rappaport. In contrast to the simultaneously appearing persisting foci, the non-persisting foci were always glycogen-poor or totally glycogen-free. Signs of cell death were frequently found in or near this type of focus. After these non-persisting foci had disappeared, the total number of pre-neoplastic lesions obviously remained constant. We conclude that this disappearance of early appearing, severely altered foci is due to cell loss caused by the non-specific toxic effect of the carcinogen.

Animals↗
PubMed1997

Myocardial damage assessed by indium-111-antimyosin: correlation with persistent enteroviral ribonucleic acid in dilated cardiomyopathy.

The persistence of enteroviral ribonucleic acid (RNA) in the myocardium has been implicated as a pathogenetic factor in idiopathic dilated cardiomyopathy. Enteroviral persistence may lead to myocardial cell membrane damage, resulting in increased uptake of antimyosin antibodies. To further evaluate this hypothesis, a direct comparison of myocardial antimyosin uptake with the presence of enteroviral RNA was performed in ten patients (one female, nine male; 53+/-8 years) with chronic dilated cardiomyopathy. Planar antimyosin images were obtained 48 h after the injection of indium-111-labelled antimyosin Fab. Using a region of interest technique, the heart to lung uptake ratio (HLR) was calculated as a semiquantitative parameter of myocardial tracer uptake. Cardiac catheterization was performed to assess left ventricular function and to obtain myocardial biopsy samples. In the biopsy samples, gene amplification by polymerase chain reaction (PCR) was used to specifically detect enteroviral RNA. In the ten patients, the left ventricular ejection fraction was 39%+/-11% and the end-diastolic volume 131+/-46 ml/m2. The HLR was 1.72+/-0.21 and showed no correlation with functional parameters. In two patients with a positive PCR consistent with persisting enteroviral RNA, the HLR was not higher than that in eight patients with a negative PCR (1.46+/-0. 18 vs 1.78+/-0.18, respectively). These results suggest that increased uptake of 111In-antimyosin in chronic idiopathic dilated cardiomyopathy cannot be explained by pure persistence of enteroviral RNA. Other pathogenetic factors such as myocardial autoantibodies or microvascular spasm may be responsible for myocyte membrane damage detected by antimyosin.

Antibodies, Monoclonal↗
PubMed1984

Herpes simplex virus persistence in mouse neuroblastoma (C 1300) cell cultures: role of interferon.

The Mp strain of herpes simplex virus type 1 (HSV1) induced a persistent infection in the mouse C 1300 neuronal cell line (clone N 115). C 1300 cultures infected at an MOI of 0.01 or 0.001 survived the initial infection and continued to produce infectious virus and viral antigens for 185 days and 31 days, respectively. Viral antigens were not detected in cultures no longer producing infectious virus; these "cured" cultures had comparable susceptibility to reinfection with HSV as previously uninfected C 1300 cells. While significant amounts of interferon were produced by C 1300 cells when challenged with Newcastle Disease Virus (NDV) or when treated with poly I:C, HSV-induced interferon could not be detected in either the acutely or persistently infected cell lines. The persistent state was not significantly altered by the addition of 1,000 units/ml of murine interferon alpha plus beta (MuIFN alpha + beta), nor was it affected by the addition of antibody to MuIFN. It appears that IFN does not play an important role in the establishment and/or maintenance of viral persistence in this neuronal system.

Animals↗
PubMed1984

Persistent infection of mouse fibroblasts with Coxsackievirus.

Infection of fibroblast cell lines initiated from BALB/c or NFR mice with coxsackievirus B3 (CBV-3) or B4 (CBV-4) resulted in infections which persisted for a limited number of subpassages of the infected cells in most cases, but for over a year in one case. In all instances primary acute infections were characterized by cytopathology and release of infectious virus progeny. Viral antigen could be detected during the acute phase of infection, but not in subcultured infected cells. Infectious center assays showed that every cell was infected during the acute phase of infection, but that from the first subcultivation on, the numbers of cells which were able to initiate infection were greatly reduced. The long term persistent CBV-3 infection was characterized by wide fluctuations in titers of virus released into the supernatant fluids. Interferon did not appear to play a role in maintenance of the persistent infection. Information derived from studies on mechanisms of CBV persistence in the in vitro model may help to elucidate the role of CBV in chronic human diseases such as myocarditis.

Animals↗
PubMed1995

Ultrastructural and replicative features of foot-and-mouth disease virus in persistently infected BHK-21 cells.

Persistent foot-and-mouth disease (FMD) virus infection in vitro has been studied in a chronically infected cloned BHK-21 cell line. Virus growth during serial cell passages was followed by infectivity assay and immunocytochemical staining. Only a small percentage of cells (0.006-6%) was found to harbour virus during persistence. Light and electron microscopy showed the presence of cytoplasmic protuberances ("blebs") at the surface of persistently infected cells. The curing of cell cultures was achieved by passaging them in the presence of polyvalent immune serum. The absence of virus in cured cells was confirmed by infectivity assay and immunocytochemistry. This finding, together with the low percentage of infected cells in cultures confirms that persistently infected BHK-21 cells satisfy the definitions of a carrier culture. The characteristics of the in vitro system and its relevance to the study of FMD carrier state in vivo are discussed.

Animals↗
PubMed1985

Influence of cellular functions on the evolution of persistent infections with Junin virus.

Vero cell cultures persistently infected with Junin virus and subjected to different cultural conditions were established. The production of infectious plaque-forming virus, ts mutants and interfering viral particles was determined at different times during 110 days after infection. Carrier cultures maintained in stationary conditions continuously released PFU while proliferating persistent cultures exhibited a cyclical pattern which tends to a rapid PFU disappearance. Concomitantly, in stationary cultures the production of interfering particles was delayed and was lower than in actively growing persistent cells. The metabolic state of the infected cells did not affect the release of ts mutants. The results suggest that a cellular function is involved on the regulation of Junin virus persistent infections.

Animals↗
PubMed1985

Monoclonal antibodies against five structural components of measles virus. II. Characterization of five cell lines persistently infected with measles virus.

Groups of monoclonal antibodies against measles virus nucleoprotein (NP), phosphoprotein (P), matrix (M), hemagglutinin (H) and fusion (F) components were used for characterization of 5 persistently infected cell lines. In four of these lines (Lu106 carrier, MaSSPE, MaPi, HEpPi) all cells were infected but the cells mostly produced noninfectious virus products. The fifth line (HNT in vero cells) did not produce any infectious virus and only a fraction of the cells were infected in most passages. In agreement with earlier findings the virus strains showed marked variations in the M epitope pattern and also some variation in the H epitope pattern. In addition epitope variations were found in both NP and P protein, which contrasted with conserved antigen characteristics of these components in lytically replicating virus. Restriction of fusion in the persistent infections was studied further. HNT and Lu 106 cells showed selective quantitative restriction in F protein synthesis. Lu106 cells were found to contain distinct epitopic F species. In contrast MaSSPE cells produced readily detectable cleaved F protein and in addition extracellular virus products carried hemolytic activity. The fact that no cell fusion occurred was interpreted to be due to particular properties of the Ma 106 cells, a concept supported by the absence of fusion of these cells when infected with syncytiogenic measles virus. It is concluded that (a) under conditions of persistence of measles-virus without requirement for synthesis of complete virions a more pronounced variation in epitope characteristics of virus components is encountered than in lytic infections; and b) that persistence of measles virus shows individualistic characteristics which may reflect changes in the virus and/or innate properties of the host cells.

Animals↗
PubMed1981

Establishment and maintenance of a persistent infection of L132 cells by human coronavirus strain 229E.

A persistent infection by human coronavirus 229E (HCV/229E) was established in a human continuous cell line (L132). Following the initial infection with stock HCV/229E, several cultures were established of which two (HV1 and HV4) have been maintained by continuous passage for two years. These cultures have shed high titres of infectious virus continuously into the supernatant fluid since their initiation. The persistently infected cells were resistant to homologous super-infection but supported polio virus replication to normal titres. Preliminary tests indicated that 50-100 percent of the cells contain virus. Neither interferon nor reverse transcriptase could be detected in these cultures and the presence of defective interfering particles could not be demonstrated. VH1 and VH4 coronaviruses, isolated from these persistently infected cultures (HV) and identified by 229E antiserum neutralization, were more cytocidal than the parent virus as judged by plaque characteristics and CPE, however they were indistinguishable on the basis of density, EM morphology, and genome size. Present evidence indicated that temperature plays an important but as yet undetermined role in the establishment and maintenance of stable 229E persistently infected cell cultures.

Antibodies, Viral↗
PubMed1982

Restriction of virus-specific protein synthesis in a persistent paramyxovirus infection.

Synthesis of virus-specific proteins in a persistent, nonproductive paramyxovirus infection derived from the peripheral blood leukocytes of a patient with subacute sclerosing panencephalitis (SSPE) was investigated. The persistently infected cells expressed cytoplasmic virus-specific antigens and generated paramyxovirus nucleocapsids throughout long-term passage. When analyzed by specific immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, most of the virus structural proteins were synthesized in acutely infected cells, but only three of the proteins could be readily detected in persistently infected cells. The two structural proteins whose synthesis was most clearly restricted had molecular weights of 69,000 and 41,000 daltons and represented the putative HN and M virus proteins. The similarities between the restriction of virus protein synthesis in this system and that reported previously for other persistent paramyxovirus infections derived from SSPE suggest that a common mechanism may be involved in the maintenance of such infections.

Amnion↗
PubMed1979

Production of temperature-sensitive and pathogenic virus from Aedes albopictus cells (Singh) persistently infected with Chikungunya virus.

When A. albopictus, clone C6/36, cells were infected with chikungunya (CHIK) virus, high virus yield accompanied by a cytopathic effect in the acute stage of infection was followed by a relatively low yield of virus over a long period of time. Virus produced from persistently infected cultures became gradually of smaller plaque size and more temperature-sensitive; however, such virus still retained pathogenicity for suckling mice even after one year of infection. When the persistently infected cells were subcultured, a dissociation was observed between the time course of cell growth and that of virus production, suggesting some intracellular mechanisms that turn off virus production. The greater part of the interference against CHIK virus by the culture medium of the persistently infected cells appeared to be mediated by the infective virus in the medium. The infective virus was easily removed from the persistently infected cells either by subculture or by cloning in the presence of anti-CHIK serum, yielding cured cultures or virus-negative clones.

Aedes↗
PubMed1982

Vascular anomalies and subarachnoid haemorrhage associated with persisting embryonic vessels.

In 25 per cent of patients with persistinc primitive trigeminal artery, and in 27 percent of patients with primitive hypoglossal artery, vascular malformations or a history of subarachnoid haemorrhage were found. There is a high incidence of aneurysms at the site of origin of the persisting embryonic vessels. No relation was found between the persisting embryonic vessels and the age, sex, and time of subarachnoid haemorrhage. Opacification of posterior cerebral arteris, vertebral arteries, and posterior communicating arteries was analysed, and variations of the Circulus arteriosus Willisi were found. Ten patients with persisting embryonic vessels are described. In patients in whom external carotid-middle cerebral artery bypass is planned, attention should be drawn to the possibility of persisting embryonic vessels.

Adult↗
PubMedDate not supplied

Colonization and persistence of Escherichia coli phenotypes in the intestines of children aged 0 to 18 months.

The aim of the present investigation was to study the intestinal colonization of Escherichia coli in newborn children, and to determine which strains become residential within the human intestine. The E. coli flora of 89 newborn children was studied by repeated sampling during their first 11 or 18 months of life. The E. coli isolates from the samples were subdivided into phenotypes by the aid of biochemical fingerprinting, a method which measures the kinetics of 24 selected biochemical tests as a tool for discriminating bacterial strains. It was found that E. coli strains colonizing children soon after birth persisted longer than strains colonizing them later. Especially those phenotypes which were defined as hospital strains persisted longer. Certain phenotypes were commonly found among the children, and these phenotypes were more persistent and more homogeneous than other phenotypes with respect to their pattern of biochemical activities. They might be specially adapted to colonize the human intestine. It was concluded that the generally long persistence of the first E. coli strains colonizing a newborn child indicates that the first case of bacterial colonization in children may be an event too important to be allowed to happen at random.

Aging↗
PubMedDate not supplied

Persistence of Borrelia burgdorferi and histopathological alterations in experimentally infected animals. A comparison with histopathological findings in human Lyme disease.

Gerbils appear to be susceptible to infection by human isolates of Borrelia burgdorferi; we obtained 100% infection. Isolation of the B. burgdorferi from different organs six months post infection causes a generalized infection thus demonstrating that borreliae persist in these animals for a long period. Spirochetemia was present for 14 days, apparently in two intervals. The Borrelia burgdorferi specific antibody titers increased with time after infection thus indicating the persistence of spirochetes. The intraperitoneal inoculation of the B. burgdorferi to six gerbils of groups A and B induced significant histopathologic changes in most of the major organ systems and their surrounding adipose and fibrous connective tissues. The infiltrates consisted mainly of lymphocytes and histiocytes. Various numbers of plasma cells, eosinophils and high numbers of mast cells were also present. Three further animals which served as controls displayed no histological signs of inflammation in any organ system. No significant differences were noted between the histopathological findings seen in the animals of groups A and B (infected with cells from subcultures no. 25 and with no. 5, respectively). The persistence of B. burgdorferi and the high number of organs involved with slight to severe signs of inflammation in this series can be compared to persistence and to the multiorgan involvement seen in human Lyme disease. Thus gerbils can serve as suitable experimental animals to study the pathogenesis of Lyme disease and the extent of organ damage caused by B. burgdorferi.

Animals↗