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J L Portis

Publications and source records attributed to J L Portis.

18 recordsLinked to original sources
PubMed1992

Murine retrovirus-induced spongiform encephalomyelopathy: host and viral factors which determine the length of the incubation period.

A molecular clone of wild mouse ecotropic retrovirus CasBrE (clone 15-1) causes a spongiform neurodegenerative disease with a long incubation period, greater than or equal to 6 months. This virus infects the central nervous system (CNS) at low levels. In contrast, a chimeric virus, FrCasE, containing env and 3' pol sequences of 15-1 in a Friend murine leukemia virus background, infects the CNS at high levels and causes a rapid neurodegenerative disease with an incubation period of only 16 days. With both viruses, the induction of neurologic disease is dependent on inoculation during the perinatal period. Since the length of the incubation period of this disease appears to be a function of the relative level of CNS infection, we have attempted to identify the viral and host factors which determine the relative level of virus infection of the CNS. It was previously shown that the CNS is susceptible to infection only during the perinatal period (M. Czub, S. Czub, F. J. McAtee, and J. L. Portis, J. Virol. 65:2539-2544, 1991). Here we have found that the susceptibility of the CNS wanes progressively or gradually as a function of the age of the host, this age-dependent resistance being complete by 12 to 14 days of age. Utilizing a group of chimeric viruses, we found that the relative level of CNS infection achieved after inoculation of mice at 1 day of age was a function of the kinetics of virus replication and spread in peripheral organs. Viruses which reached peak viremia titers early (5 to 7 days of age) infected the CNS at high levels, and viruses which reached peak titers later infected the CNS at lower levels. Among the group of viruses examined in the current study, the kinetics of peripheral virus replication and spread appeared to be influenced primarily by sequences within the R-U5-5' leader region of the viral genome. These results suggested that the relative level of CNS infection was determined very early in life and appeared to be a function of a dynamic balance between the kinetics of virus replication in the periphery and a progressively developing restriction of virus replication in the CNS.

Aging↗
PubMed1991

Murine retrovirus-induced spongiform encephalopathy: productive infection of microglia and cerebellar neurons in accelerated CNS disease.

We have examined the pathological lesions and sites of infection in mice inoculated with a highly neurovirulent recombinant wild mouse ecotropic retrovirus (FrCasE). The spongiform lesions appeared initially as swollen postsynaptic neuronal processes, progressing to swelling in neuronal cell bodies, all in the absence of detectable gliosis. Infection of neurons in regions of vacuolation was not detected. However, high level infection of cerebellar granule neurons was observed in the absence of cytopathology, wherein viral protein was found associated with both axons and dendrites. Infection of ramified and amoeboid microglial cells was associated with cytopathology in the brain stem, and endothelial cell-pericyte infection was found throughout the CNS. No evidence of defective retroviral expression was observed. These results are consistent with an indirect mechanism of retrovirus-induced neuropathology.

Animals↗
PubMed1991

The R-U5-5' leader sequence of neurovirulent wild mouse retrovirus contains an element controlling the incubation period of neurodegenerative disease.

The wild mouse ecotropic retrovirus CasBrE causes a spongiform neurodegenerative disease after neonatal inoculation, with an incubation period ranging from 2 to 12 months. We previously showed that introduction of long terminal repeat (LTR) and gag-pol sequences from a strain of Friend murine leukemia virus (FB29) resulted in a dramatic acceleration of the onset of the disease. The chimeric virus FrCasE, which consisted of the FB29 genome containing 3' pol and env sequences from the wild mouse virus, induced a highly predictable, lethal neurodegenerative disease with an incubation period of only 16 days. Here we report that the sequences which are primary determinants of the length of the incubation period are located in the 5' end of the viral genome between a KpnI site in the R region of the LTR and a PstI site immediately 5' of the start codon for pr65gag (R-U5-5' leader). This region contains the tRNA primer binding site, splice donor site for the subgenomic env mRNA, and the packaging sequence. Computer-assisted sequence analysis failed to find evidence of a consensus sequence for a DNA enhancer in this region. In addition, sequences within a region of the genome between a ClaI site at the 3' end of env to the KpnI site in the R region of the LTR (inclusive of U3) also influenced the incubation period of the disease, but the effect was distinctly weaker than that of the R-U5-5' leader sequence. This U3 effect, however, appeared to be independent of the number of direct repeats, since deletion of one of two duplicated 42-base repeats containing consensus sequences of nuclear-factor binding domains had no effect on the incubation period of the disease. On the basis of Southern blot analysis of total viral DNA in the tissues, the effect of these sequences on the incubation period appeared to be related to the level of virus replication in the central nervous system. All of the chimeric viruses analyzed, irrespective of neurovirulence, replicated to comparable levels in the spleen and induced comparable levels of viremia.

Amino Acid Sequence↗
PubMed1991

Age-dependent resistance to murine retrovirus-induced spongiform neurodegeneration results from central nervous system-specific restriction of virus replication.

The murine retrovirus CasBrE causes a noninflammatory spongiform degeneration of the central nervous system (CNS). Mice inoculated as neonates develop viremia and are susceptible to disease. However, mice inoculated at 10 days of age do not develop viremia and are totally resistant to the neurologic disease. We recently described a highly neurovirulent chimeric virus, FrCasE (J. L. Portis, S. Czub, C. F. Garon, and F. J. McAtee, J. Virol. 64:1648-1656, 1990), which contains the env gene of CasBrE. Mice inoculated at 10 days of age with this virus developed a viremia comparable to that in neonatally inoculated mice but, surprisingly, were still completely resistant to the neurodegenerative disease. A comparison of the tissue distribution of virus replication for mice inoculated at 1 or 10 days of age was determined by Southern blot analysis for the quantification of viral DNA and by infectious-center assay for the quantification of virus-producing cells. The levels of virus replication in the spleens were comparable in the two groups. In contrast, virus replication in the CNS of the resistant 10-day-old mice was markedly restricted (100- to 1,000-fold). Intracerebral inoculation did not overcome this restriction. A similar pattern of CNS-specific restriction of virus replication and resistance to disease was observed in athymic NIH Swiss nude mice inoculated at 10 days of age, suggesting that T-cell immunity was not involved. From our results, we conclude that the age-dependent resistance to disease is a consequence of the restriction of virus replication within the CNS due to the developmental state of the organ.

Aging↗
PubMed1990

Host genes conferring resistance to a central nervous system disease induced by a polytropic recombinant Friend murine retrovirus.

Infection of certain strains of mice with the ecotropic Friend murine leukemia virus results in the generation of recombinant polytropic mink cell focus-inducing viruses and the development of erythroleukemia. We isolated a Friend mink cell focus-inducing virus (F-MCF-98D) from a Friend murine leukemia virus-infected BALB/c mouse which caused primarily a neurological disease as well as a low incidence of leukemia in susceptible IRW mice. Through genetic studies with the resistant C57BL/10 strain, we identified two genes which correlated with restricted viral replication and resistance to the development of disease caused by F-MCF-98D. One gene correlated with the expression of an endogenous gp70 linked to the Rmcf gene and might act by viral interference. The mechanism of action of the second gene was less clear, but it appeared to be associated with development of an antiviral antibody response.

Animals↗
PubMed1990

Neurodegenerative disease induced by the wild mouse ecotropic retrovirus is markedly accelerated by long terminal repeat and gag-pol sequences from nondefective Friend murine leukemia virus.

The wild mouse ecotropic retrovirus (WM-E) induces a spongiform neurodegenerative disease in mice after a variable incubation period of 2 months to as long as 1 year. We isolated a molecular clone of WM-E (15-1) which was weakly neurovirulent (incidence, 8%) but was highly leukemogenic (incidence, 45%). Both lymphoid and granulocytic leukemias were observed, and these leukemias were often neuroinvasive. A chimeric virus was constructed containing the env and 3' pol sequences of 15-1 and long terminal repeat (LTR), gag, and 5' pol sequences from a clone of Friend murine leukemia virus (FB29). FB29 has been shown previously to replicate to high levels in the central nervous system (CNS) but is not itself neurovirulent. This finding was confirmed at the DNA level in the current study. Surprisingly, intraperitoneal inoculation of neonatal IRW mice with the chimeric virus (FrCasE) caused an accelerated neurodegenerative disease with an incubation period of only 16 days and was uniformly fatal by 23 days postinoculation. Introduction of the LTR of 15-1 into the FrCasE genome yielded a virus (FrCasEL) with a degree of neurovirulence intermediate between those of 15-1 and FrCasE. No differences were found in the levels of viremia or the relative levels of viral DNA in the spleens of mice inoculated with 15-1, FrCasE, or FrCasEL. However, the levels of viral DNA in the CNS correlated with the relative degrees of neurovirulence of the respective viruses (FrCasE greater than FrCasEL greater than 15-1). Thus, the env and 3' pol sequences of WM-E (15-1) were required for neurovirulence, but elements within the LTR and gag-pol regions of FB29 had a profound influence on the level of CNS infection and the rate of development of neurodegeneration.

Animals↗
PubMed1979

Changes in the transplantability of a virus-induced murine leukemia tumor.

The subcutaneous growth potential of a Friend virus-induced murine leukemia cell line (FBL-3) passaged in the ascites form was found to change, depending on the interval of time spent in the peritoneal cavity. Injection sc of the original stock of FBL-3 (growth continuously in vitro) into C57BL/10 mice produced transient tumors uniformly rejected by days 20-40. The tumor cells passaged in the ascites form for 7 days behaved like the in vitro-grown cells, whereas ascites cells harvested at 14 days produced progressive lethal subcutaneous tumors in 50-70% of the recipients. The change in subcutaneous growth was reversible simply by alteration of the ascites passage schedule. Day 7 ascites cells (regressors) were converted to progressors by ip passage for 14 days, and day 14 ascites cells (progressors) were converted to regressors by ip passage for 7 days. The difference in growth potential between day 7 and day 14 ascites cells was not due to effects of nonneoplastic host cells accompanying the tumor cells in the ascites population, because neither dilution of nonneoplastic cells by in vitro culture nor selective killing of H-2a/b host cells by anti-H-2 serum and complement altered the subcutaneous growth behavior or either day 7 or day 14 ascites cells. These results indicated that the change in the growth potential of FBL-3 occurred at the level of the tumor cells. However, no quantitative differences were observed in the expression of serologically detectable tumor-associated antigens by these two populations. Possible mechanisms for this change in transplantability were considered.

Animals↗
PubMed1979

Deposition of IgA in renal glomeruli of mink affected with Aleutian disease.

The glomerular deposition of immunoglobulin (Ig) was studied in sapphire mink affected with terminal Aleutian disease (AD). Fluorescein conjugated Ig-class specific antiserums were used to evaluate and identify the glomerular Ig. Kidneys of all 28 mink with documented AD had deposits of IgA and beta 1 C in a capillary and mesangial distribution. Only 7 of 28 mink had demonstrable glomerular IgG and/or IgM. In addition, interstitial plasma cell infiltrates in 17 of 19 kidneys stained exclusively with anti-IgA. All antiserums used in this study were evaluated for Ig-class specificity by both gel diffusion and agarose-bead techniques. The striking Ig class restriction demonstrated for glomerular Ig deposition in AD is discussed in light of current knowledge of the pathogenesis of AD glomerulopathy.

Aleutian Mink Disease↗
PubMed1978

Vascular permeability changes in the central nervous system of rats with hyperacute experimental allergic encephalomyelitis induced with the aid of a substance from Bordetella pertussis.

Development of hyperacute experimental allergic encephalomyelitis in Lewis rats after intraperitoneal administration of a mixture of guinea pig spinal cord emulsion and pertussigen from Bordetella pertussis was accompanied by an increase in vascular permeability in the central nervous system. The increased permeability was most striking in the spinal cord and seemed to be associated with the ascending development of paralysis. Rats that had completely recovered from paralysis did not have any increased permeability in the central nervous system. Rats which developed paralysis after inoculation with either guinea pig spinal cord emulsion alone or with complete Freund adjuvant had only a small degree, if any, of increased permeability in the vascular system of the central nervous system.

Acute Disease↗
PubMed1976

Immune response in the garter snake (Thamnophis ordinoides).

Garter snakes (Thamnophis ordinoides) were immunized with hen egg albumin, human gamma-globulin and Keyhole limpet haemocyanin in Freund's adjuvant. Antibody was consistently detected by radioimmunoelectrophoresis and in three different gamma- and beta-globulin precipitin lines called IgM (approximately or equal to 20S), Ig-1 (approximately or equal to 9S) and Ig-2 (approximately or equal to 8-5S). Early antibody (day 31 after immunization) was frequently Ig-M whereas Ig-2 and especially Ig-1 were detectable for the longest duration (992 days). After immunization with antigen in Freund's adjuvant, Ig-1 serum concentration showed the greatest increase, from almost undetectable levels to the most prominent immunoglobulin in immune serum.

Animals↗
PubMed1976

Immune response in the hamster. VIII. Ig class differences in susceptibility to tolerance induction.

A hemolytic plaque assay was used to quantitate the antibody response of the Syrian hamster after immunization with hen egg albumin (HEA). Whereas HEA in complete Freund's adjuvant (HEA-CF) induced a prolonged heterogeneous (IgM, IgG1 and IgG2) antibody response, the response to soluble HEA in saline (HEA-S) differed in that: 1)both the primary and secondary responses were restricted to the IgG1 class; 2)the IgG1 primary response was cyclical with PFC peaks on days 9 and 16; 3)although an anamnestic secondary response was demonstrated, no further augmentation was noted after tertiary and quaternary boosters; 4)the booster response was transient reaching a peak after 48 hr and declining to low levels within 7 days. Adoptive transfer of lymph node cells to irradiated recipients followed by challenge with HEA-CF revealed: 1)that HEA-S-treated donor cells were primed for an IgG1 response because anamnesis was seen 7 days after challenge, yet on day 21, IgG1 PFC were 20-fold less than that of controls; 2)recipients of HEA-S treated cells showed profound suppression of both IgM and IgG2 PFC on days 14 and 21. These studies indicate that soluble antigen induced in hamsters a state of complete tolerance of IgM and IgG2 classes whereas the anamnestic response of the IgG1 class remained intact.

Animals↗
PubMed1975

The immune response in the hamster. VII. Studies on cytophilic immunoglobulin.

Hamster 7S IgG1 and IgG2 antibodies to hen-egg albumin (HEA) were tested for their capacity to bind to macrophage cytophilic Ig receptors. Both IgG1 and IgG2 were cytophilic for hamster macrophages though the membrane receptor had a predominant specificity for IgG1. Hamster IgG1 bound primarily to homologous macrophages whereas IgG2 bound to macrophages from other rodent species as well. The binding of hamster Ig to hamster macrophages was inhibited by a wide range of heterologous rodent sera. The only exception was guinea pig serum since guinea pig IgG2 was found to bind only to homologous macrophages. Sheep red blood cells (SRBC) coated with hamster IgG2 were ingested by macrophages more readily than those coated with hamster IgG1. Thus, there appeared to be a paradoxical relationship between the apparently strong affinity of IgG1 for the hamster macrophage Ig receptor and its reactivity weak ingestion promoting activity. Implications of this phenomenon are discussed.

Absorption↗