Biomedical subjects

C A Mims

Publications and source records attributed to C A Mims.

At least 37 records · Page 2Linked to original sources

PubMed1985

Enhancing antibodies, macrophages and virulence in mouse cytomegalovirus infection.

The infectivity of tissue culture-passed mouse cytomegalovirus (MCMV) for resident mouse peritoneal macrophages in the presence of serial dilutions of antiviral antibody was studied by fluorescent antibody staining and virus yields. Although MCMV was neutralized by high concentrations of antiserum, there was a twofold enhancement of infectivity by subneutralizing antibody concentrations. On further dilution of antiserum, significant neutralization appeared again. When F(ab')2 fragments of anti-MCMV IgG were used or when macrophages were pretreated with monoclonal antibody to Fc receptor, there was no enhancement, and no neutralization at high dilutions of antiserum. This suggests that both enhancement and high dilution neutralization are mediated via the Fc portion of IgG and Fc receptors of macrophages. Tissue culture-passed virus whose infectivity for macrophages was reduced by high dilutions of antibody was converted to a more infectious state by addition of anti-mouse immunoglobulin. Similar results were obtained with salivary gland virus, which is less infectious for macrophages and is coated with non-neutralizing antibody. Tissue culture-passed virus is known to be less virulent for suckling mice and more infectious for macrophages than salivary gland-passed virus. When tissue culture-passed virus was coated with appropriately diluted antiviral antibody, not only was its infectivity for macrophages reduced, but it also became more virulent than control virus treated with normal mouse serum. These results are interpreted in terms of the optimal density of Fc on the virus-immunoglobulin complex in relation to the density of Fc receptors on macrophages.

Animals↗

PubMed1985

Association of virulence of murine cytomegalovirus with macrophage susceptibility and with virion-bound non-neutralizing antibody.

A comparison was made of the virulence in vivo and the infectivity in vitro for macrophages of (i) tissue culture-passed mouse cytomegalovirus (MCMV), (ii) salivary gland virus taken 3 weeks after infection (SGV 3w), and (iii) salivary gland virus taken 1 week after infection (SGV 1w). Salivary gland virus (3w) is known to be coated with non-neutralizing antibody, and is more virulent for newborn suckling mice and less infectious for macrophages than tissue culture-passed virus (TCV). Properties of SGV 1w were similar to those of TCV. Infectivity of SGV 3w for macrophages was significantly enhanced by treatment with trypsin (10 micrograms/ml) and at the same time virulence was lost. When SGV 1w or TCV were treated with trypsin the infectivity for macrophages was unaltered as long as the inoculum was adjusted to contain the same number of p.f.u. as assayed in MEF. Trypsin-treated SGV 3w was neutralized not by rabbit anti-mouse IgG Fc, but by anti-Fab, whereas untreated virus was neutralized by both of these anti-mouse immunoglobulins. These results are discussed in terms of the association of virulence with virion-bound antibody and Fc receptors on macrophages.

Animals↗

PubMed1985

Ia antigens and Fc receptors of mouse peritoneal macrophages as determinants of susceptibility to lactic dehydrogenase virus.

The relationship between susceptibility of mouse peritoneal macrophages to lactic dehydrogenase-elevating virus (LDV) infection and expression of I region-coded antigens (Ia) on these cells was investigated. The proportion of Ia-positive cells in resident peritoneal macrophages from adult and suckling mice were 4 to 10% and 50 to 70% respectively. Approximately the same percentage of the cells were susceptible to LDV, as detected by fluorescent antibody staining. In adult mice, double-labelling experiments showed that most of the Ia-positive cells were LDV-infected. When the cells were cultured for more than 24 h in vitro, Ia-positive cells rapidly disappeared and the culture became resistant to LDV. Removal of Ia-positive cells by treatment with anti-Ia plus complement or enrichment using an anti-Ia-coated Petri dish simultaneously removed or enriched for LDV-susceptible cells. Treatment of cells with trypsin (1 mg/ml) removed their I-A and I-E antigens and simultaneously abolished susceptibility for LDV. When LDV was preincubated with subneutralizing amounts of antibody, infectivity for macrophages was enhanced and the proportion of LDV-infected cells was higher than that of Ia-positive cells. This suggests that Fc receptors on macrophages can act as receptors for LDV coated with antiviral IgG.

Animals↗

PubMed1985

Differential susceptibility of cultured neural cells to the human coronavirus OC43.

By using cell-type-specific markers and neural cultures derived from various areas of the nervous system, it has been possible to identify various interactions between OC43 virus and mouse oligodendrocytes, neurons, astrocytes, and fibroblasts. Neurons derived from dorsal root ganglia produced viral antigen and infectious virus. Astrocytes and fibroblasts both produced viral antigen but not infectious virus. Oligodendrocytes produced neither infectious virus nor viral antigen. Human embryo brain cells, including astrocytes, were susceptible to OC43 infection but did not produce infectious virus.

Animals↗

PubMed1985

Synthesis of antibodies, including antiviral antibodies, in the knee joints of patients with arthritis.

Serum and synovial fluids from 16 patients with seronegative arthritis and eight with rheumatoid arthritis were studied for immunoglobulin levels and for antibody levels to five viruses. When allowances were made for the distribution of immunoglobulins between serum and synovial fluid there was evidence that in several patients antibody to one or more viruses was synthesised locally in the joint. IgG and especially IgM were present in greatly increased amounts in arthritic joints compared with normal joints. On the basis of serum/synovial fluid ratios inflammation and local immunoglobulin synthesis are discussed as possible causes. These results are compared with antiviral antibody and immunoglobulin ratios observed in the serum and cerebrospinal fluid of patients with multiple sclerosis.

Antibodies, Viral↗

PubMed1985

Alopecia in mice infected with murine cytomegalovirus (MCMV).

When mouse cytomegalovirus was injected subcutaneously into 4-12 day old CDI mice there was infection of dermal cells and the dermal papillae of hair follicles. Infected cells were never seen in the epidermis nor in the epithelium of hair follicles. When larger doses of virus (5 X 10(4) pfu) were given, dermal infection led to gross necrosis of the skin, ulceration, scabbing and healing with alopecia. Smaller doses (10(4) pfu) did not cause gross necrosis but damage to follicles resulted in alopecia or sparse hair growth. Skin lesions were not seen after infection of 4-8 week old mice, even when the inoculated skin area had been epilated, or when hyaluronidase was mixed with the virus inoculum. These experiments show that cytomegalovirus, in contrast to herpes simplex and varicella-zoster viruses, infects dermal but not epidermal cells, and that dermal tropism is age-restricted.

Alopecia↗

PubMed1984

Effects of pregnant mouse serum and pregnancy hormones on the replication in vitro of murine cytomegalovirus.

When mouse embryo fibroblasts cultivated in medium containing 2 per cent pregnant mouse serum were infected with mouse cytomegalovirus they gave 3-4 fold greater plaque counts and virus yield than when the medium contained 2 per cent normal mouse serum. Plaque size was increased up to two fold. There were similar differences between 2 per cent foetal calf serum and 2 per cent calf serum. When medium containing 2 per cent dialysed fetal calf serum was supplemented with physiological concentrations of oestrogen, progesterone and corticosteroid there was a 2-3 fold increase in plaque count and virus yield. The increase was only seen when the hormones were present both during virus adsorption and throughout virus replication. Any one of the hormones added by itself gave a smaller and more variable increase in yield and/or plaque count. Growth hormone by itself gave a 2 fold increase in virus yield; when added to the three other hormones it gave a 7-13 fold increase in virus yield but little change in plaque count. The three hormones also increased the rate of infection of resident peritoneal macrophages as scored by fluorescent antibody staining after a single cycle of virus growth in vitro. These experiments suggest that mouse cytomegalovirus infecting a pregnant mouse, or reactivating in a pregnant mouse would replicate more extensively.

Animals↗

PubMed1983

Selective vulnerability of neural cells and age-related susceptibility to OC43 virus in mice.

Suckling CD 1 mice infected intracerebrally or extraneurally with OC43 virus developed a lethal neurotropic infection with high titres of virus in the brain. Examination of infected brain by routine H & E staining revealed no necrosis even in extensively infected tissue. Resistance to infection developed with increasing age, and by 20 days of age mice were completely insusceptible to i.c. inoculation. Virus replication was also demonstrable by FA staining, in spinal cord, dorsal root ganglia and retina. All other tissues were insusceptible and in particular, macrophages from both susceptible and resistant mice were found to be resistant to infection both in vivo and in vitro. Immunosuppression rendered 15 day old mice more susceptible to infection but adult mice remained insusceptible. The transfer of immune or non immune spleen cells from resistant mice did not confer resistance to newborn mice. Treatment of resistant mice with anti interferon globulin (AIG) did not render them more susceptible. These results indicate that the immune response is partially responsible for the development of resistance to OC43 infection but that it is only partially protective and other factors must also be required. The basis for the unique susceptibility of neural tissues in suckling mice is being investigated.

Aging↗

PubMed1983

Antigen-specific suppression of delayed type hypersensitivity to murine cytomegalovirus in MCMV-infected mice.

When primary infection with murine cytomegalovirus (MCMV) was by the intravenous route, the resulting delayed type hypersensitivity (DTH) to MCMV was reduced compared with subcutaneous or intraperitoneal infection. Intravenous injection of 10(3) or more p.f.u. of MCMV also reduced the DTH response to virus injected at the same time subcutaneously. When spleen cells from mice injected intravenously with MCMV 1 to 3 weeks earlier were transferred to subcutaneously infected mice, the resulting DTH response was suppressed. The cells responsible were T cells, being non-adherent and Thy-1 positive; they were not destroyed by complement plus antibody to either Lyt-1 or Lyt-2. Suppression was not transferred by serum. The suppression was antigen-specific; DTH responses induced by sheep red blood cells and by a thymidine kinase-negative strain of herpes simplex virus type 1 were not significantly suppressed by concurrent intravenous infection with MCMV. Suppression of DTH to MCMV caused by intravenously injected MCMV was reduced in mice given 50 mg/kg cyclophosphamide, but not in those given 200 mg/kg. Deoxyguanosine had no effect on the induction of DTH to MCMV.

Animals↗

PubMed1983

Interferon as a defence mechanism in mouse cytomegalovirus infection.

Mouse cytomegalovirus (MCMV) grew to higher titres in spleen, liver, kidney and salivary gland of mice, and caused more sickness and death in susceptible (CD1) mice following treatment with anti-interferon globulin (AIG). In the resistant (C3H) strain of mice, organ titres were higher following AIG treatment but there was no sickness or mortality. Spleen necrosis was more severe in AIG-treated mice, indicating that this necrosis was not caused by interferon-mediated activation of natural killer (NK) cells. CD1 mice developed a high level of NK activity during MCMV infection and this was greatly reduced by AIG treatment. AIG was equally effective in increasing virus titres in NK-deficient beige (bg/bg) C57 B1.6 mice which showed a low level of NK activity even after MCMV infection, suggesting that interferon protects against MCMV by its direct antiviral effect on cells rather than by activating NK cells.

Animals↗

PubMed1983

Rash produced by mouse cytomegalovirus.

A striking rash was produced in mice 4 days after intravenous injection of large doses of murine cytomegalovirus. Routine histology showed cell infiltration, vascular damage, and hemorrhage. Immunofluourescent staining showed dermal but not epidermal infection, and this appeared to be initiated after the localization in small blood vessels of circulating virus or of virus-containing leukocytes. The rash was accompanied by a high level of complement-requiring neutralizing antibodies in the serum and extensive deposition of immune complexes in the renal glomeruli containing immunoglobulin G, immunoglobulin M, and complement. When mice were depleted of complement by cobra venom factor, when antibody responses were reduced by cyclophosphamide treatment, or when a prostaglandin inhibitor (indomethacin) was given, the rash was much less severe. The role of direct viral damage and inflammatory and immune responses in the genesis of the lesions is discussed.

Aging↗

PubMed1983

Chronic arthritis associated with the presence of intrasynovial rubella virus.

In this report we present 21 instances in which live rubella virus was isolated from synovial fluid obtained from 6 cases of inflammatory oligoarthritis or polyarthritis over a period of 2 years in the absence of firm clinical evidence of rubella. In 3 cases (cases 1, 2, 6,) a persistent oligoarthritis predominantly affecting the knee joints occurred in 2 adult women and one man, lasting to date 27, 29, and 18 months respectively, and in one of these cases virions were found in cells of the synovial membrane. In case 3 a boy of 9 presented with an illness indistinguishable from the systemic variety of juvenile chronic arthritis (Still's disease). In case 4 a young man with persistent monoarthritis was found to have ankylosing spondylitis, and in case 5 a progressive erosive polyarthritis developed 5 years after an attack of rubella complicated by rubella arthritis. The virus was identified by a variety of virological techniques and infection confirmed by immunofluorescence and (in one case) electron microscopy.

Adult↗

PubMed1982

Influenza virus replication in human alveolar macrophages.

Studies with animal models suggest that alveolar macrophages may be important cells in some respiratory virus infections, but little is known about the role of these cells in virus infections in man. In this study human alveolar macrophages were obtained by fibreoptic bronchoscopy and infected in vitro with a variety of influenza viruses. After infection with the NWS strain of influenza virus the haemagglutinin and nucleoprotein viral antigens were demonstrated in greater than 90% of cells at 24 h by immunofluorescence with specific antisera. There was no cytopathic effect at this time, and no virus release was detected by plaque assay of culture fluids on MDCK cells. Alveolar macrophages were also infected with a human vaccine strain (H1N1) of influenza virus and with two recent isolates (H1N1 and H3N2). In each case viral nucleoprotein antigen was produced in 10-20% of the cells by 24 h postincubation, but there was no release of infectious virus. There was no cytopathic effect and the phagocytosis of IgG-coated latex beads was unimpaired 24 h after in vitro infection.

Cells, Cultured↗

PubMed1982

Role of macrophage activation and interferon in the resistance of alveolar macrophages from infected mice to influenza virus.

Lung macrophages from uninfected CD1 mice support the replication of influenza viruses (H1N1 and H0N1), but the cells from influenza-infected mice do not. The possible mechanisms of this resistance were investigated. Murine macrophages were "activated" in vitro with lipopolysaccharide and lymphokines, and in both cases activation was associated with resistance of cells to infection with influenza virus. Exposure of alveolar macrophages in vitro to 500 U of purified type I interferon per ml enhanced cell spreading and Fc receptor-mediated phagocytosis, suggesting macrophage activation, and protected the cells against infection with influenza virus. Alveolar macrophages were also protected by a soluble factor in the bronchoalveolar washings from influenza-infected mice. This effect was not virus specific and was abolished by anti-interferon serum.

Animals↗

PubMed1982

Delayed hypersensitivity to murine cytomegalovirus and its depression during pregnancy.

A delayed hypersensitivity skin test for murine cytomegalovirus is described, in which ear swelling is measured after injection of heat-killed virus. The response appeared within 4 days of infection, peaked at 8 days, and remained at high levels for at least 100 days. When live virus was inoculated into the ear of previously uninfected mice, a much greater degree of ear swelling was seen, maximal at 7 days, but without growth of virus in the inoculated ear. Mice infected with avirulent (cell culture-passaged) virus gave greater delayed hypersensitivity responses than with those infected with virulent (salivary gland-passaged) virus. One of the strains of mice that is susceptible to murine cytomegalovirus (C57BL) developed greater delayed hypersensitivity responses than did the resistant strain (C3H). The delayed hypersensitivity response of neonatally infected mice was greatly depressed during pregnancy and lactation.

Animals↗

PubMed1981

Isolation of rubella virus from synovial fluid in five cases of seronegative arthritis.

A cytopathic agent indistinguishable from rubella virus was isolated from the synovial fluid of five patients (two male and three female). In two patients isolations were made on two separate occasions, and in two others on five separate occasions. The patients ranged in age from 9-58 years, and they presented with a variety of clinical syndromes. In particular, none had clinical features suggestive of recent rubella infection; but most cases had very high serum rubella haemagglutination inhibition titres. The identity of the cytopathic agent was shown by a variety of virological techniques to be rubella virus.

Adult↗

PubMed1981

Neutralization of different strains of murine cytomegalovirus (MCMV)-effect of in vitro passage.

Two strains of mouse cytomegalovirus (MCMV) propagated in mouse salivary glands could be distinguished in neutralization tests. Cell (mouse embryo fibroblast)-passaged virus of either strain was generally 10-20 times easier to neutralize than virus produced in mouse salivary glands. Evidence was obtained that mouse immunoglobulin was attached to virus particles in salivary gland preparations. First, antibody to mouse immunoglobulin inactivated salivary gland virus but not cell culture-grown virus. Second, virus obtained from mice early after infection, before antibody production, was as easy to neutralize as cell culture-grown virus. The attached immunoglobulins were CMV-specific, non-neutralizing, and interfered with the action of neutralizing antibody. Non-neutralizing antibodies that bind to infectious virus particles are present in mouse serum at the time salivary glands are harvested, 3 weeks after infection.

Animals↗

PubMed1981

Murine cytomegalovirus particle types in relation to sources of virus and pathogenicity.

Murine cytomegalovirus (MCMV) preparations from mouse embryo fibroblasts and from infected salivary glands were purified on potassium tartrate density gradients and examined by electron microscopy. The cell culture virus contained multicapsid enveloped virions which are ruptured easily and account for the excess number of free capsids in these preparations. Salivary gland virus consisted of single-capsid enveloped virus and equal numbers of free capsids. Particle types were imperfectly separated on density gradients, but successful separation was achieved by filtration through 220 and 450 nm Millipore membrane filters. Naked capsids were not infectious and could not be rendered infectious by centrifugal adsorption, showing that centrifugal enhancement of MCMV infectivity is not mediated through this mechanism. Although present in excess number in (avirulent) cell culture virus preparations, naked capsids did not interfere with the action of (virulent) salivary gland virus in newborn mice.

Animals↗