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At least 343 records · Page 19Linked to original sources
PubMed1998

Characterization of defective viral RNA produced during persistent infection of Vero cells with Murray Valley encephalitis virus.

Defective interfering viral particles are readily produced in cell culture after a high multiplicity of infection with many animal RNA viruses. Due to defects that they carry in their genomes, their life cycle needs to be complemented by the helper functions provided by a parental virus which makes them both dependent on and competitive with the parental virus. In many instances, this may cause the abrogation of a lytic cycle of the parental virus, leading to a persistent infection. In this paper, we describe for the first time the presence of truncated or defective interfering viral RNAs produced in Vero cells persistently infected with the flavivirus Murray Valley encephalitis virus. While these RNAs have not been detected in acutely infected Vero cells, their appearance coincided with the establishment of persistent infection. We also show for the first time that the defective viral RNAs replicate well in both cell culture and cell-free virus replication systems, indicating that they may interfere with the replication of parental virus at the level of viral RNA synthesis. Significantly, structural analyses of these RNA species including nucleotide sequencing have revealed that they carry similar nucleotide deletions encompassing the genes coding for the prM and E proteins and various gene segments coding for the N terminus of the NS1 protein. These deletions are in frame, allowing the synthesis of truncated NS1 proteins to occur in persistently infected cells. This may have further implications for the interference with the parental virus at the level of viral RNA synthesis in addition to a major one at the level of virion assembly and release.

Animals↗
PubMed2000

Detection of human papillomavirus type 16 DNA in consecutive genital samples does not always represent persistent infection as determined by molecular variant analysis.

Persistent human papillomavirus (HPV) infection of the uterine cervix is a risk factor for progression to high-grade squamous intraepithelial lesions. Detection in consecutive genital samples of HPV-16 DNA, a frequently encountered HPV type, may represent persistent infection or reinfection. We undertook a study using PCR-single-strand conformation polymorphism (SSCP) analysis and sequencing of PCR products (PCR-sequencing) to determine if consecutive HPV-16-positive samples contained the same HPV-16 variant. Fifty women (36 human immunodeficiency virus [HIV] seropositive, 14 HIV seronegative) had at least two consecutive genital specimens obtained at 6-month intervals that contained HPV-16 DNA as determined by a consensus L1 PCR assay. A total of 144 samples were amplified with two primer pairs for SSCP analysis of the entire long control region. Fifteen different SSCP patterns were identified in our population, while 22 variants were identified by PCR-sequencing. The most frequent SSCP pattern was found in 75 (53%) samples from 27 (54%) women. The SSCP patterns obtained from consecutive specimens were identical for 46 (92%) of 50 women, suggesting persistent infection. Four women exhibited in consecutive specimens different HPV-16 SSCP patterns that were all confirmed by PCR-sequencing. The additional information on the nature of persistent infection provided by molecular variant analysis was useful for 6% of women, since three of the four women who did not have identical consecutive specimens would have been misclassified as having persistent HPV-16 infection on the basis of HPV typing.

Adult↗
PubMed1985

Group B coxsackieviruses readily establish persistent infections in human lymphoid cell lines.

Exposing human lymphoid cell lines to uncloned or recently cloned group B coxsackieviruses results in the frequent establishment of chronically infected cultures. Persistence is maintained by a carrier culture mechanism involving virus spread through the medium and replication among a minority of cells at any given time. These studies provide a model for persistence by highly cytocidal viruses.

Cell Line↗
PubMed1994

Epizootiological studies of hantavirus infection among urban rats in Hokkaido, Japan: evidences for the persistent infection from the sero-epizootiological surveys and antigenic characterizations of hantavirus isolates.

Epizootiological studies of hantavirus infection among urban rats were carried out through the surveys repeated 11 times at the same dumping ground area in 1983 to 1988. A total of 279 rats (Rattus norvegicus) were captured during the surveys. Sero-positive animals to hantavirus strain SR-11 were detected in all the surveys. Overall positive rate of rats 6 months old or more (94/128, 73.4%) was significantly higher than that of younger rats (23/151, 15.2%, x2 = 96.4, P < 0.001). Therefore, age dependent acquisition of hantavirus infection among rats was confirmed. Seven hantavirus strains, KI-83-262 (August, in 1983, designated as strain KI-262 in our previous report (2)), KI-85-1 and 85-2 (July in 1985), KI-88-4, 88-11, 88-15 and 88-24 (October, 1988) were isolated from lung tissues of adult rats which have high titers of neutralizing antibody. Although the serum specimens of virus carrier rats neutralized the infectivity of all the KI isolates, no apparent antigenic change in the isolates was detected by indirect immunofluorescent antibody (IFA) assay using polyclonal and monoclonal antibodies (MAbs) regardless of isolation years. However, neutralization test showed slight difference of antigenicity among KI strains. These results epizootiologically confirmed that hantavirus infected persistently among urban rats in a presence of neutralizing antibody.

Animals↗
PubMed1992

Stimulation of lymphokines in Jurkat cells persistently infected with vaccinia virus.

The response of the human CD4+ T-cell line Jurkat to infection with vaccinia virus was investigated. Virus titers peaked approximately 3 to 4 days after infection, while cell growth paralleled that of uninfected cells, indicating that growth rates were not appreciably affected by viral infection. Results from plaque assays and fluorescence-activated cell sorter (FACS) analyses of virus antigens demonstrated that a persistent infection in which the percentage of infected cells and the virus titers fluctuated from passage to passage was established. Further characterization of the persistent infection revealed that the virus influences cellular functions. Induction of interleukin-2 (IL-2) and IL-2 receptor alpha (IL-2R alpha) in Jvac cells was shown by enzyme-linked immunosorbent assay and FACS analysis, respectively. Hybridization of cellular RNA with cloned probes confirmed the increased IL-2 expression and demonstrated that Jvac cells also expressed more IL-6 but not gamma interferon (IFN-gamma) or IL-1 beta. Dual-antibody staining and FACS analysis for vaccinia virus antigens and IL-2R alpha indicated that IL-2R alpha expression was restricted to the infected cells. Jvac cells were also resistant to superinfection, an additional proof that persistent infection elicited phenotypic changes in the cell population.

CD4-Positive T-Lymphocytes↗
PubMed1991

Western blot analysis of antibody specificities in subacute sclerosing panencephalitis: reactivity to measles virus proteins produced in persistently infected cells.

The specificity of serum antibodies from patients with subacute sclerosing panencephalitis (SSPE) and seropositive controls to measles virus proteins produced in acutely and persistently infected human cells was examined by western blot analysis. Sera from both SSPE patients and controls reacted to the H, N, and F1 virus proteins produced in acutely infected AV3 cells. However, while SSPE-derived sera reacted with the same proteins in persistently infected cells (AV3Al/MV), most control sera failed to react with the hemagglutinin protein produced in such cells (Hp). Most sera also reacted poorly with the M protein from either source, and the reactivity to the P protein was variable. Although the exact reason(s) for the different reactivities to the proteins were not determined, differences in antibody concentration did not appear to be responsible. The dramatic differences in the reactivity of SSPE and control sera to the Hp protein suggest that either the protein coevolves in persistent infections or multiple forms of the protein evolve in such infections and SSPE patients develop broad-spectrum humoral immunity as a consequence of exposure to them. Alternatively, over time there may be selective loss of some H-reactive antibody subsets by individuals who contract measles, but do not develop SSPE.

Adolescent↗
PubMed1981

Curing of virus persistent infection in HVJ (sendai virus) carrier hamster tumor cells by transplantation.

Transplantability of hamster tumor cells in the syngeneic system was considerably reduced by HVJ (Sendai virus) persistent infection of the cells, but these HVJ carrier cells still showed tumorigenicity, especially at high transplantation doses. Therefore, the existence of HVJ antigens or infectious HVJ in the tumors formed in vivo by transplanted HVJpi (temperature-sensitive HVJ) or HVJo (non-temperature-sensitive HVJ) carrier tumor cells was examined in relation to the reduced transplantability of the cells. In stamp preparations of tumors cells, no HVJ antigens were detected from 14 days after transplantation, though they were positive if observed within 7 days. Infections HVJ particles could also be recovered from tumor tissues which were cocultivated with LLCMK2 cells within 7 days after transplantation. However, tumor cells recultured in vitro after more than 3 weeks post transplantation did not show HVJ antigens, even after various attempts at HVJ induction such as culture at low temperature, serial passages in vitro, treatment with 5-iododeoxyuridine, etc. The cytopathic effects and fluorescent antibody staining of these cells became positive when they were superinfected with wild-type HVJ, indicating a new establishment of HVJ infection after the curing of the HVJ genome initially carried. In contrast, the original HVJ carrier tumor cells were demonstrated to be completely resistant to this superinfection (one of the characteristics of persistent infection). These results seem to show that HVJ persistence in its carrier tumor cells was ultimately cured by transplantation and may provide at least a partial explanation of why the xenogenization of tumor cell by HVJ persistent infection was relatively weak.

Animals↗
PubMed1980

Establishment and maintenance of persistent infection by Sindbis virus in BHK cells.

We have established a persistent infection of BHK cells with a preparation of Sindbis virus heavily enriched in defective interfering (DI) particles. The small fraction of cells that survived the initial infection grew out to form a stable population of cells [BHK(Sin-1) cells], most of which synthesized viral RNA and viral antigens. The presence of DI particles in this virus stock was required to establish this persistent state. BHK(Sin-1) cells released a small-plaque, temperature-sensitive virus (Sin-1 virus) as well as DI particles containing DI RNAs larger than those present in the original stock used to establish the persistent state. A cloned stock of Sin-1 virus, free of detectable DI particles, was able to initiate a persistent infection more quickly and with greater cell survival than the original stock of Sindbis virus containing DI particles. About 2 weeks after the Sin-1 virus-infected cells were cultured, DI RNAs arose and soon became the dominant viral RNA species produced by these cells.

Animals↗
PubMed1988

Decrease of oligo-2',5'-adenylate synthetase activity in BALB3T3 cell persistently infected with Moloney murine leukemia virus.

The induction of oligo-2',5'-adenylate synthetase (2-5AS) activity by interferon (IFN) was decreased in BALB3T3 cells persistently infected with Moloney murine leukemia virus (Mo-MLV) as compared with uninfected cells. Furthermore, the correlation between increased susceptibility to vesicular stomatitis virus (VSV) infection and reduced 2-5AS activity was recognized in the Mo-MLV persistently infected cells. The decrease of enzyme activity was confirmed by a solid phase reaction and an analysis of reaction products by Fast Polynucleotide Liquid Chromatography (FPLC) in addition to a liquid phase reaction. In a solid-phase reaction, the enzyme protein binds to polyinosinate-cytidylate (Poly I:C) agarose beads and other cellular proteins can be washed out from the reaction mixtures. Therefore, these results indicate that the decrease of IFN-induced enzyme activity is due to the suppression of transcription and/or translation of 2-5AS mRNA. A decreased amount of 2-5AS mRNA in persistently infected cells was observed by Northern blot and dot-blot hybridization. On the other hand, cell lysate of Mo-MLV infected cells inhibited the 2-5AS activity in liquid phase reaction. The inhibition may also be partly due to the degradation of oligo-2',5'-adenylate (2-5A) formed by 2-5AS.

2',5'-Oligoadenylate Synthetase↗
PubMed1990

Sendai virus gene expression in lytically and persistently infected cells.

Sendai virus RNA species were quantitated in lytically and persistently infected cultured cells by Northern blot hybridization to region- and strand-specific cloned cDNA probes. Levels of NP, P and M mRNA in lytically infected cells were equally high, but F and HN mRNA were present in about 3-fold, and L mRNA in 30-fold, lower amounts, reflecting transcriptional attenuation especially at the M-F and HN-L gene junction. Two persistently infected cell lines, which release only 1% of the virus particles of lytically infected cells, were shown to contain only 4- to 8-fold-less amounts of each viral mRNA and 2- to 3-fold-less genomic RNA than lytically infected cells. Additionally, transcription was neither defective nor more attenuated as compared to the lytical infection. Taken together the results suggest the existence of an additional regulatory mechanism for the virus release. A cell-associated state of infection therefore seems to be achievable by a relatively weak general reduction of the copy numbers of viral mRNA and genomic RNA.

Animals↗
PubMed1999

Risk factors for coronary heart disease and persistent infection with Chlamydia pneumoniae or cytomegalovirus: a population-based study.

BACKGROUND: A large number of epidemiological and pathological studies have reported on associations between coronary heart disease and persistent infection with Chlamydia pneumoniae or cytomegalovirus, but relatively few have reported on possible relations between these infections and vascular risk factors. OBJECTIVE: To determine whether serum concentrations of immunoglobulin G antibodies to C. pneumoniae or cytomegalovirus are correlated to standard vascular risk factors, markers of inflammation and indicators of socioeconomic status. METHODS: We performed a cross-sectional sero-epidemiological study nested within a randomized trial involving five general practices in Bedfordshire, UK. We made measurements of a number of standard vascular risk factors, serum markers of systemic inflammation and other relevant characteristics in 704 individuals. RESULTS: There were significant associations between C. pneumoniae immunoglobulin G levels and male sex and cigarette smoking (2P < 0.01 for each) and between cytomegalovirus immunoglobulin G levels and age (2P < 0.001). Other factors were not significantly associated with serum antibodies to either persistent infection. CONCLUSIONS: Serological evidence of persistent infection with C. pneumoniae or cytomegalovirus in this population was not strongly associated with most standard vascular risk factors and other characteristics. The main implication is that such risk factors are not likely to be important confounders or mediators of the reported associations between coronary heart disease and these agents.

Adult↗
PubMed1982

Effects of compromising agents on candidosis in mice with persistent infections initiated in infancy.

Oral-intragastric inoculation of infant CFW mice with Candida albicans, leading either to lethality or to persistent infection of long duration, provides a useful model for study of the host-pathogen interrelationships in candidosis. Mice were most susceptible to the lethal effects of challenge when 4 to 6 days of age, increasingly resistant up to 10 to 11 days, and then resistant to doses of C. albicans lethal for the younger animals. Older mice harboring persistent infections of the gastrointestinal tract, originally initiated when the animals were 6 days old, were used to study the effects of agents which commonly are administered to cancer patients or which are known to predispose to candidosis. The broad-spectrum antibiotic chloramphenicol, cortisone acetate, X-irradiation, or single high doses of cyclophosphamide (Cytoxan) resulted in markedly enhanced levels of C. albicans in the gastrointestinal tract without systemic spread. Repeated smaller doses of Cytoxan, or treatment with methotrexate or a combination of cortisone acetate and Cytoxan, produced gastrointestinal candidosis associated with invasion and systemic spread. The data indicate that the persistently infected animals provide a realistic model for studying treatments that precipitate candidosis in humans.

Aging↗
PubMed2025

SARS-CoV-2 genomic diversity and within-host evolution in individuals with persistent infection in the UK: an observational, longitudinal, population-based surveillance study.

BACKGROUND: Persistent SARS-CoV-2 infections in hospitalised immunocompromised individuals are known to facilitate accelerated within-host viral evolution, potentially contributing to the emergence of highly divergent variants. However, little is known about the evolutionary dynamics and transmission risks of persistent infections in the general population. We aimed to characterise the within-host evolution of SARS-CoV-2 during persistent infections identified through a large community surveillance study. METHODS: We used data from the Office for National Statistics COVID-19 Infection Survey (ONS-CIS), a large-scale, longitudinal, population-based surveillance study conducted in the UK from April, 2020, to March, 2023. For this analysis, we focused on infections with high viral load (cycle threshold &#x2264;30) and available genome sequences, from seven major SARS-CoV-2 lineages (alpha, delta, BA.1, BA.2, BA.4, BA.5, and XBB). ONS-CIS participants were randomly selected from the general population and tested regularly by RT-PCR, regardless of symptoms. We defined persistent infections as those with sustained or rebounding high viral RNA titres for 26 days or longer. We examined associated host characteristics and used raw sequence data to identify de novo mutations and estimate within-host synonymous and non-synonymous evolutionary rates across the SARS-CoV-2 genome. FINDINGS: Between Nov 2, 2020, and March 21, 2023, we identified 576 persistent infections with at least two sequences, including 11 alpha, 106 delta, 102 BA.1, 204 BA.2, 16 BA.4, 133 BA.5, and 4 XBB. Persistent infections were more common in males than females (p<0&#xb7;0001) and individuals older than 60 years (p=0&#xb7;0027). The median within-host genome-wide evolutionary rate was 7&#xb7;9&#x2009;&#xd7;&#x2009;10-4 substitutions per site per year (IQR 7&#xb7;0-9&#xb7;0&#x2009;&#xd7;&#x2009;10-4), with high inter-individual variability driven largely by non-synonymous mutations, particularly in the N-terminal and receptor-binding domains of the spike protein. Longer infection duration was associated with higher evolutionary rates, while no associations were found with age, sex, vaccination status, previous infection, or virus lineage. We found no clear evidence of transmission beyond the first month of infection in any of the 84 persistent infections lasting 56 days or longer. In total, we identified 379 recurrent mutations, including many with known or predicted negative fitness effects and low prevalence at the population level, as well as de novo reversions to the Wuhan-Hu-1 reference sequence, which were likely under positive selection within those individuals. INTERPRETATION: This study highlights the heterogeneous nature of within-host SARS-CoV-2 evolution in individuals with persistent infection in the community. Notably, a small subset of persistent infections with high viral loads underwent accelerated viral evolution or recurrently acquired hallmark mutations found in novel variants. In addition, onward transmission from a persistent infection during the later stages of infection is likely to be rare. These insights have important implications for prioritising genomic surveillance and managing patients with persistent infections. FUNDING: Department of Health and Social Care.

Humans↗
PubMed1995

Inhibition of apoptosis in human immunodeficiency virus-infected cells enhances virus production and facilitates persistent infection.

Apoptosis is one of several mechanisms by which human immunodeficiency virus type 1 (HIV-1) exerts its cytopathic effects. CD4+ Jurkat T-cell lines overexpressing the adenovirus E1B 19K protein, a potent inhibitor of apoptosis, were used to examine the consequences of inhibition of apoptosis during acute and chronic HIV-1 infections. E1B 19K protein expression inhibited HIV-induced apoptosis, enhanced virus production, and established high levels of persistent viral infection. One E1B 19K-expressing line appeared to undergo HIV-induced death via a nonapoptotic mechanism, illustrating that HIV infection results in lymphocyte depletion through multiple pathways. Increased virus production associated with sustained cell viability suggests that therapeutic approaches involving inhibition of HIV-induced programmed cell death may be problematic.

Adenovirus E1B Proteins↗
PubMed1985

Base mutations in the terminal noncoding regions of the genome of vesicular stomatitis virus isolated from persistent infections of L cells.

The 3'-terminal regions of the genomes of vesicular stomatitis virus obtained from two long-term, independently initiated persistent infections of L cells were found to contain several sequence mutations. In contrast to the hypermutability displayed in the 5'-terminal regions of the genomes of viruses obtained from persistent infections of baby hamster kidney (BHK) cells (P. J. O'Hara, F. M. Horodyski, S. T. Nichol, and J. J. Holland, J. Virol. 49, 793-798, 1984), no 5' mutations were detected in viruses from L-cell carrier lines. The absence of detectable defective interfering (DI) particles in the L-cell carrier cultures may account for this difference. Plus-strand leader RNA made by the viruses from persistently infected L cells failed to accumulate from 5 to 8 hr postinfection unlike the accumulation noted for the leader RNA generated by wild-type VSV. Minus-strand leader RNA, on the other hand, accumulated at a similar or increased rate compared to wild type. The relationship of these observations to the processes of host shutoff, viral transcription, and replication are discussed.

Animals↗
PubMed1984

Persistent infection of human fibroblasts by hepatitis A virus.

Infection of human embryo fibroblasts with hepatitis A virus (HAV), a picornavirus, leads to an inapparent, persistent infection; cultures can be passed serially with consistent recovery of the virus in the supernatant. All of the cells of a HAV carrier culture are infected and proliferate. Subcultivation under HAV-immune serum cannot achieve a cure or even a reduction in the number of infected cells in HAV carrier cultures. No interferon activity can be detected during HAV infection and persistence. Addition of exogenous interferon eliminates HAV infection in vitro. Persistence of HAV in vitro appears to contradict the clinical course of HAV infection in vivo. The system presented offers the possibility of evaluating the role of immunological injury of HAV-infected cells, an injury which may lead to damage of these cells and to elimination of HAV during an HAV infection in vivo.

Carrier State↗
PubMedDate not supplied

[Persistent infection caused by the Coxsackie B3 virus in adult mice].

A model of persistent infection with Coxsackie B-3 virus was developed in adult mice with clinical manifestations of the disease and long-term (up to 13 months) excretion of the causative agent. The method of multiple organ cultures was shown to be suitable for isolation of the persisting enterovirus. The presence of persistent infection was confirmed by the detection of IgM antibody in repeated daily examinations of the animals for 4 months. It seems to be expedient to use this model for investigations of the pathogenesis and methods of treatment of persistent Coxsackie B-3 infection in experimental animals.

Animals↗