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At least 559 records · Page 31Linked to original sources
PubMed1994

A thymidine kinase-negative HSV-1 strain establishes a persistent infection in SCID mice that features uncontrolled peripheral replication but only marginal nervous system involvement.

A detailed knowledge of the pathogenesis of infections caused by thymidine-kinase (TK)-deficient herpes simplex virus type 1 (HSV-1) strains is important because such mutants can arise during treatment of HSV infections with acyclovir--especially in immunocompromised patients--and also because TK-negative mutants may become useful for the therapy of intracranial tumors. In this work, we studied the pathogenesis of a genetically engineered TK-negative HSV-1 strain dlsptk, in SCID mice (mice with severe combined immunodeficiency) after corneal infection. We found that dlsptk established a persistent infection that kills SCID mice within 80.2 +/- 21.3 days. The cause of death seemed to be related to uncontrolled viral replication in the superficial and deep facial tissues of the animals. Viremia probably did not occur, as judged by the inability to detect infectious virus and viral gene expression in various internal organs. However, the virus did reach the nervous system, most probably by axonal transport from the primary site of the infection. Virus-specific DNA reached low but detectable levels in the trigeminal ganglia and the brainstems by 7 days p.i. and remained at low levels for up to 50 days p.i. as determined by spot blot analysis. By in situ hybridization and immunostaining we determined that, in some of the neurons of the trigeminal ganglia infected by the virus, viral latency was established. However, our results suggested that in other infected neurons viral replication occurred and virus spread to surrounding nonneuronal cells and to the central nervous system. This work provides a new model in which the pathogenesis of infections caused by TK-deficient HSV strains in immunocompromised hosts can be effectively studied and which may also help to identify the potential side effects of the therapy of intracranial tumors with TK-negative HSV strains.

Animals↗
PubMed1984

Effects of exogenous interferon on L cells persistently infected with Sendai virus.

A carrier culture of L cells persistently infected with Sendai virus (steady state) designated as L-Sendaits cells was established with a temperature-sensitive strain of the virus. When interferon was added to culture fluids from the start of the cultures at permissive (35 degrees C) or non-permissive temperature (38 degrees C), cell-associated infectivity was unaffected at 35 degrees C, while it was unexpectedly enhanced at 38 degrees C, although the cell-associated infectivity was titrated after further incubation at 32 degrees C for 2 days. The titer of cell-associated infectivity was increased by subculturing in the continuous presence of interferon at 38 degrees C. The effect of interferon on the paradoxical enhancement of cell-associated infectivity was shown to be dose dependent. When L-Sendaits cells were successively subcultured 6 times at 38 degrees C in the continuous presence or absence of interferon, more than 95 per cent of the cells contained a detectable amount of nucleocapsid (NP) antigen in the presence of interferon, whereas the antigen could be detected in only 30-40 per cent of the cells subcultured in the absence of interferon. Only when the cells subcultured at 38 degrees C in the presence of interferon were transferred to permissive temperature, could the distinct hemadsorbing and cell-associated hemagglutinating activities and the release of virus particles, as measured by hemagglutinating activity in the culture fluids, be detected. Cells subcultured in the presence of interferon accumulated more virus polypeptides than in the absence of interferon. Accumulation of virus specific RNA in the cells subcultured in the presence of interferon was about twice as much as that in the absence of interferon. Larger sized RNA (probably 50S) was the major species and two smaller RNAs could be detected in both the treated and untreated cells. When L-Sendaits cells were cultured at 38 degrees C in the presence of interferon, their multiplication was clearly inhibited. However, the cells which were subcultured twice at 38 degrees C in the continuous presence of interferon acquired resistance to the anti-cell proliferative action of interferon. Interestingly, the conversion of the sensitive state to resistant state of the cells was reversible.

Animals↗
PubMed1985

Increase of virus yields and releases of Borna disease virus from persistently infected cells.

Borna disease virus grows to low titres in persistently infected cells with an infectious particle to cell ratio of 0.01 to 0.05. Inclusion of n-butyrate in the growth medium enhances infectivity yields up to 1 log. This effect is time and concentration dependent. In hypertonic medium with an excess of NaCl, KCl or Na2SO4 up to 50% of the total infectious virus yield is released from the cells. Released supernatant virus (buoyant density in sucrose rho = 1.22 g/cm3) is more heat stabile than cell-bound virus (rho = 1.18 g/cm3). The access to cell-free (released) virus opens new possibilities for the characterization of this neurotropic agent.

Animals↗
PubMed1976

Analysis of baby hamster kidney cells persistently infected with lymphocytic choriomeningitis virus.

Baby hamster kidney cells were persistently infected with lymphocytic choriomeningitis (LCM) virus (BHKpi cells). After 21 passages of the BHKpi cells infectious virus could no longer be detected; however, the cultures continued to produce LCM virus particles which interfered with the replication of infectious LCM virus in BHKpi cells and protected mice from a subsequent intracranial inoculation of infectious LCM virus. Cultures of BHKpi cells appeared to consist of three cell populations: uninfected cells, infected cells containing infectious LCM virus, and infected cells releasing interfering particles of LCM virus.

Animals↗
PubMed1978

Some ultrastructural effects of persistent infections by the rickettsia Coxiella burnetii in mouse L cells and green monkey kidney (Vero) cells.

Mouse fibroblasts (L-929) and Vero (green monkey kidney) cells were infected with the rickettsia Coxiella burnetti, and persistent infections developed and were studied over a 6- to 10-month period. Ultrastructural comparisons were made between the two infected cell types, and both were tested cytochemically for the presence of acid phosphatase, a marker enzyme of lysozymes. Rickettsiae were always observed within vacuoles, and some infected L cells showed flattened endoplasmic reticulum as compared with uninfected cells. Rickettsiae in Vero cells were most often seen in vacuoles containing whorls of membranes ("myelin configurations") which were also seen in uninfected cells. Rickettsiae in Vero cells were pleomorphic, with acid phosphatase reaction product in their periplasmic space. This suggests either rickettsial degradation by lysosomal enzymes which penetrated the cell envelope or a penetration after the rickettsiae were dead. Vacuoles of infected Vero cells showed much more reaction product than that in infected L cells, and most rickettsiae in L cells had a normal appearance and showed no reaction product in their periplasmic space.

Acid Phosphatase↗
PubMed1979

Novel antiviral activity found in the media of Sindbis virus-persistently infected mosquito (Aedes albopictus) cell cultures.

Aedes albopictus (mosquito) cells persistently infected with Sindbis virus for a period of 6 months release into the medium a low-molecular-weight material capable of specifically reducing the yields of Sindbis virus during the "acute phase" of infection in mosquito cells. The antiviral activity was produced in detectable levels at 3 days after infection, and its concentration in the extracellular medium increased thereafter. The antiviral activity was inactivated by treatment with the enzyme protease K and heat. It was not activated by treatment with antibody prepared against extracts of Sindbis virus-infected BHK-21 cells. The antiviral activity differs from interferon produced by vertebrate cells in that it is virus specific as well as cell specific.

Aedes↗
PubMed1986

Establishment of a Vero cell line persistently infected with African swine fever virus.

A Vero cell line persistently infected with African swine fever virus was established by infecting the cells in the presence of 10 mM NH4Cl (Vero-P cell line). The virus derived from the Vero-P cultures infected Vero cells, and virus titers were comparable to those obtained in Vero cells acutely infected with African swine fever virus. The structural proteins of the virus from Vero-P cells were similar to those of the virus produced in lytic infections. Virus production was low when the Vero-P cells were growing logarithmically and increased considerably in confluent cultures when lysis appeared in a fraction of the cell population.

African Swine Fever Virus↗
PubMed1987

Differences among human immunodeficiency virus strains in their capacities to induce cytolysis or persistent infection of a lymphoblastoid cell line immortalized by Epstein-Barr virus.

Four strains of human immunodeficiency virus (HIV) manifest consistent differences in biologic behavior after infection of the X50-7 line of human umbilical cord lymphocytes immortalized by Epstein-Barr virus (EBV). Some dilutions of the first strain examined, human T-cell lymphotropic virus type III B, which is derived from a pool of patient isolates propagated in H9 cells, caused transient cytopathic effects (CPE) followed by recovery of a subpopulation of X50-7 cells which became virus carrier cultures. Other dilutions of the same virus stock completely lysed X50-7 cells. Two other strains, RF2 and YW, both from individual patients with acquired immune deficiency syndrome, always induced complete cytolysis of X50-7 cells at all dilutions which infected the cells. However, RF2 did establish persistent infection of H9 cells. A fourth strain, PH1-MN, from a child with acquired immune deficiency syndrome-related complex, induced only transient CPE in X50-7 and H9 cells, which thereafter always recovered to form carrier cultures. For all four strains, the dilutions of HIV stocks which caused CPE corresponded to dilutions which resulted in the detection of HIV polypeptides by immunoblot. Cytolysis in HIV-infected X50-7 cells was accompanied by a decrease in the amount of EBV nuclear antigen; however, HIV infection did not induce EBV replication. Thus CPE in X50-7 cells is due to replication of HIV per se and not to activation of EBV. The observations indicate that there are differences in the cytolytic properties of HIVs and that these differences are influenced by the target cell.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Transmission studies with simian immunodeficiency virus of macaques; persistent infection of baboons.

The host range of SIVmac was investigated in three monkey species. Blood-borne and cell-adapted virus inocula obtained from a rhesus macaque infected with SIVmac251 were compared. African green monkeys were not susceptible to infection, whereas baboons and rhesus macaques became persistently infected and showed similar patterns of seroconversion. However, in contrast to the macaques, no clinical or histopathological evidence of disease was seen in the baboons 2 years after virus inoculation. Thus baboons could be used as an alternative to macaques in vaccine development studies with this particular isolate of SIVmac. Furthermore, this system may be useful for the investigation of factors responsible for disease progression.

Animals↗
PubMedDate not supplied

Characteristics of a macrophage culture persistently infected with herpes simplex virus type 1.

BACKGROUND: Persistence of herpes simplex type 1 (HSV-1) has been reported in sensory neurons, corneal epithelium, and lymphocytes, although other cell types such as macrophages should also be considered as hosts for HSV-1 persistence. Here we report the establishment and characterization of HSV-1 persistence in an immortalized murine macrophage-like cell line (P388D1). METHODS: The persistently HSV-1 infected culture (P388D1per) was obtained from surviving P388D1 macrophages infected with HSV-1 MP strain at multiplicity of 0.001. P388D1per was characterized by [corrected] extracellular production of viruses, cells expressing viral antigens, and cells releasing infectious viruses. Viral plaque size and cytophatic effect were determined in viruses (HSVA and HSVB) obtained from two different P388D1per passages. Host and viral proteins were detected in P388D1per and in P388D1 cells infected with HSV-1 by metabolic [35S]-methionine labeling assays. RESULTS: P388D1per culture was characterized [corrected] by cyclic production of infectious viruses from non-detectable to 10(6) TCID50/mL, [corrected] from 1.0 to 15.0% cells expressing viral antigens and macrophages released infectious viruses from 0.008 to 12.5%. Differences in viral plaque size and cytopathic effect morphology between HSVA, HSVB and HSV-1 were observed. Similar patterns of viral proteins were observed in P388D1per and in P388D1 infected with HSV-1. Nonetheless, the characteristic interference effect of HSV-1 on host protein synthesis was not observed in P388D1per culture. CONCLUSIONS: An HSV-1 persistently infected immortalized macrophage culture was established and characterized. Virus produced during persistence showed phenotypic alterations with respect to the original virus. P388D1per cell protein synthesis was not affected by the presence of HSV-1.

Animals↗
PubMed1996

Use of persistent infections with vaccinia virus recombinants to introduce alterations in foreign proteins: an application to HIV-1 env protein.

With the aim of generating a virus-cell system to introduce alterations in proteins of interest--which may be of use in studies of their biological functions--we established a persistent infection on a B-lymphoma cell line (A20.2J) with vaccinia virus (VV) recombinants. As a model, we used a vaccinia virus recombinant expressing the human immunodeficiency virus HIV-1 env gene. In this unique virus-cell system, we found that it is possible to introduce several structural and functional alterations in the env protein with passage numbers. From passage 10-20, two new env products emerged: an uncleaved gp160 and a glycoprotein fragment of 110 kDa. The uncleaved gp160 exhibit interesting properties as an immunogen. This protein forms stable oligomers, is not released from the cells, cannot fuse CD4+ presenting HeLa cells and activates a stronger cellular immune response than the parental cleaved env. In contrast, the 110 kDa product is a poor immunogen, since it lacks the gp41 domain, cannot form oligomers, accumulates intracellularly and cannot fuse CD4+ cells. In the persistently infected cells we have also found alterations in another heterologous protein-beta-galactosidase-a gene inserted in the same locus of VV as the env gene. This alteration resulted in a truncation of the (beta-galactosidase protein from 125 kDa to about 70 kDa. A similar size truncation of env and of beta-galactosidase was observed in many of the isolated VV recombinants.

Animals↗
PubMed1983

Progressive invasion of cell nuclei by measles virus in persistently infected human cells.

The distribution of measles virus antigens in an auto-degenerating persistently infected human cell line (AV3A1/MV) was examined by a direct fluorescent antibody technique. The appearance of virus antigens in cell nuclei increased with time and passage number, and correlated to a decrease in cell replication rates and increases in cellular pathology and mortality. Nuclei which had been invaded by virus antigens were frequently swollen and the cells tended to have round rather than cuboidal morphologies. The correlation between cell degeneration and viral nuclear invasion in this system suggests that quantification of viral nuclear invasion may be useful as a pathological marker of relative cell morbidity in persistent measles virus infections.

Amnion↗
PubMed1996

Productive persistent infection of hematopoietic cells by human foamy virus.

Human foamy virus can establish persistent infections in human hematopoietic cell lines, such as H92.1.7 (erythroblastoid cells), Jurkat (CD4+ T cells), and U937 (myeloid-monocytic cells). The infection is characterized by constant production of infectious viruses (for > 2 1/2 years) with no cytopathic effects on the host cells. Electron microscopy of the infected cells showed a viral morphology similar to that observed for particles produced after acute infection. We have detected, in addition to the full-length form of bel1, a previously described deletion in the bel1 gene of the proviral DNA in these cells. RNA containing this 301-bp deletion, which mapped to the splice donor and acceptor sites of the intron of the bet gene, was also found in encapsidated virion RNA. However, the presence of this defective provirus harboring the deletion in bel1 does not prevent productive persistence in these chronically infected cells, since the virus titer does not decrease during cultivation.

Base Sequence↗
PubMed1993

St Louis encephalitis virus establishes a productive, cytopathic and persistent infection of Sf9 cells.

The Sf9 cell line, commonly used for gene expression by recombinant baculovirus, has been productively infected by St Louis encephalitis (SLE) virus, a flavivirus. SLE viral infection produced a c.p.e. in the Sf9 cells characterized by giant cells and the presence of 10-fold fewer cells in the infected cultures after the first week of infection compared with uninoculated control cultures. Infected Sf9 cells expressed SLE viral antigens, and intracellular virus particles were observed by electron microscopy. Titres of cell-associated SLE virus rose slightly over an 8 week period, whereas titres of cell-free virus remained stable, suggesting that SLE virus establishes a productive and persistent infection of Sf9 cells. The SLE virus produced by the Sf9 cells could be neutralized by SLE virus-immune mouse ascitic fluid, and no evidence of escape mutants was detected. Sf9 cells persistently infected with SLE virus could be superinfected with a recombinant baculovirus and expressed recombinant antigen. The successful infection of Sf9 cells by SLE virus represents the first report of production of c.p.e. by SLE virus in insect cells under routine cell culture conditions and of the infection of Sf9 cells by a human pathogen.

Animals↗
PubMed2004

Persistent infection with ebola virus under conditions of partial immunity.

Ebola hemorrhagic fever in humans is associated with high mortality; however, some infected hosts clear the virus and recover. The mechanisms by which this occurs and the correlates of protective immunity are not well defined. Using a mouse model, we determined the role of the immune system in clearance of and protection against Ebola virus. All CD8 T-cell-deficient mice succumbed to subcutaneous infection and had high viral antigen titers in tissues, whereas mice deficient in B cells or CD4 T cells cleared infection and survived, suggesting that CD8 T cells, independent of CD4 T cells and antibodies, are critical to protection against subcutaneous Ebola virus infection. B-cell-deficient mice that survived the primary subcutaneous infection (vaccinated mice) transiently depleted or not depleted of CD4 T cells also survived lethal intraperitoneal rechallenge for >/==" BORDER="0">25 days. However, all vaccinated B-cell-deficient mice depleted of CD8 T cells had high viral antigen titers in tissues following intraperitoneal rechallenge and died within 6 days, suggesting that memory CD8 T cells by themselves can protect mice from early death. Surprisingly, vaccinated B-cell-deficient mice, after initially clearing the infection, were found to have viral antigens in tissues later (day 120 to 150 post-intraperitoneal infection). Furthermore, following intraperitoneal rechallenge, vaccinated B-cell-deficient mice that were transiently depleted of CD4 T cells had high levels of viral antigen in tissues earlier (days 50 to 70) than vaccinated undepleted mice. This demonstrates that under certain immunodeficiency conditions, Ebola virus can persist and that loss of primed CD4 T cells accelerates the course of persistent infections. These data show that CD8 T cells play an important role in protection against acute disease, while both CD4 T cells and antibodies are required for long-term protection, and they provide evidence of persistent infection by Ebola virus suggesting that under certain conditions of immunodeficiency a host can harbor virus for prolonged periods, potentially acting as a reservoir.

Acute Disease↗
PubMed2000

Establishment of a cell line persistently infected with bovine herpesvirus-4 by use of a recombinant virus.

Bovine herpesvirus-4 (BHV-4), a gammaherpesvirus lacking a clear disease association, productively infects multiple cell lines of various species and causes cell death. A human rhabdomyosarcoma cell line, RD-4, infected with BHV-4 produced low levels of early and late viral RNAs and infectious virus, but exhibited no cytopathic effect. Using a recombinant BHV-4 containing a neomycin-resistance gene, we established RD-4-derived cell lines persistently infected with BHV-4. The viral genome in these cells was predominantly circular. Because of drug selection, every cell contained a viral genome. In addition, all cells stained with a BHV-4-specific antiserum. Therefore, these cell lines are not carrier cultures. These cells produced infectious virus at all passages tested. Even though cells were selected and maintained at a concentration of geneticin at least 2.5 times that necessary to kill uninfected RD-4 cells, selected cells contained only approximately one viral genome per diploid host cell genome. Persistently infected cells grew more slowly than uninfected cells, even in the absence of drug. The slower growth of these cells suggests that any growth advantage conferred by multiple copies of the neomycin-gene-carrying viral genome might be offset by the detrimental effects of viral gene expression. This situation contrasts with other gammaherpesviruses, which are able to growth-transform cells.

Animals↗
PubMed1995

Detection of bovine viral diarrhoea virus antigen and RNA in oviduct and granulosa cells of persistently infected cattle.

Large-scale in vitro bovine embryo production systems commonly use genital tracts obtained from an abattoir as a source of both cumulus-oocyte complexes and co-culture feeder cells. Tissues derived from this source may be contaminated with non-cytopathogenic bovine viral diarrhoea virus (BVDV) since, in several countries surveyed, approximately 1% of animals tested are persistently infected with this pathogen. Therefore, the use of such material in in vitro fertilization systems presents a potential risk for the transmission of BVDV to bovine embryos and via embryo transfer. This potential was investigated by obtaining oviduct epithelial cells and granulosa cells, which are commonly used as feeder cells, from cattle persistently infected with BVDV and examining them for the presence of BVD viral antigen (p80 non-structural protein and gp53 envelope glycoprotein) by indirect immunofluorescent histochemistry, and also viral RNA (encoding the p80 region) by in situ hybridization. In addition, titres of virus present in oviduct, ovary and blood were assayed by immunodetection on calf testis cell cultures. Luminal epithelial cells from the oviduct and primary cultures of granulosa cells and oviduct epithelial cells from such cattle were shown to contain both viral antigen and RNA. The susceptibility of both cell types to BVDV infection was further established by inoculating primary cell cultures of cells derived from cattle not infected with BVDV with a cloned isolate of non-cytopathogenic BVDV (Pe515). RNA encoding BVDV and the antigen were detected 12 h after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗