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G W Anderson

Publications and source records attributed to G W Anderson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Relationship between virulence and immunity as revealed in recent studies of the F1 capsule of Yersinia pestis.

Yersinia pestis, the causative agent of plague, possesses multiple virulence determinants encoded on its three plasmids and on its chromosome. We evaluated the role of the protein capsule F1 in virulence an immunity against plague. Strains lacking F1, either those that are naturally occurring or those with genetically defined nonpolar mutations in the structural gene, retained their virulence for mice and nonhuman primates. However, both active immunization with F1, from either a recombinant vector or Y. pestis, and passive immunization with F1 monoclonal antibody protected mice from experimental infection with wild-type F1-positive organisms. These results suggest that protective immunogens like F1 need not be essential for virulence. The rare isolation of virulent F1-negative organisms from F1-immunized animals infected with F1-positive strains supports this conclusion and also suggests that, in addition to F1, an optimal vaccine against plague should include essential virulence factors as immunogens.

Animals↗
PubMed1995

Lactate dehydrogenase-elevating virus entry into the central nervous system and replication in anterior horn neurons.

The initial replication of lactate dehydrogenase-elevating virus (LDV) in mice, its invasion of the central nervous system (CNS) and infection of anterior horn neurons in C58 and AKXD-16 mice were investigated by Northern and in situ hybridization analyses. Upon intraperitoneal injection, LDV replication in cells in the peritoneum was maximal at 8 h post-infection (p.i.). Next, LDV infection was detected in bone marrow cells and then in macrophage-rich regions of all tissues investigated (12 to 24 h p.i.). By 2 to 3 days p.i., LDV RNA-containing cells had largely disappeared from all non-neuronal tissues due to the cytocidal nature of the LDV infection of macrophages. In the CNS at 24 h p.i. LDV replication was very limited and confined to cells in the leptomeninges. LDV replication in the cells of the leptomeninges should result in the release of progeny LDV into the cerebrospinal fluid and thus its dissemination throughout the CNS. However, in C58 and AKXD-16 mice, which are susceptible to paralytic LDV infection, only little LDV RNA and few LDV-infected cells were detectable in the spinal cord until at least 10 days p.i. Extensive cytocidal infection of anterior horn neurons occurred only shortly before the development of paralytic symptoms between 2 and 3 weeks p.i. The reason for the relatively long delay in LDV infection of anterior horn neurons is not known. No LDV RNA or LDV RNA-containing cells were detected in the brain, except in the leptomeninges at early times after infection.

Animals↗
PubMed1995

Infection of central nervous system cells by ecotropic murine leukemia virus in C58 and AKR mice and in in utero-infected CE/J mice predisposes mice to paralytic infection by lactate dehydrogenase-elevating virus.

Certain mouse strains, such as AKR and C58, which possess N-tropic, ecotropic murine leukemia virus (MuLV) proviruses and are homozygous at the Fv-1n locus are specifically susceptible to paralytic infection (age-dependent poliomyelitis [ADPM]) by lactate dehydrogenase-elevating virus (LDV). Our results provide an explanation for this genetic linkage and directly prove that ecotropic MuLV infection of spinal cord cells is responsible for rendering anterior horn neurons susceptible to cytocidal LDV infection, which is the cause of the paralytic disease. Northern (RNA) blot hybridization of total tissue RNA and in situ hybridization of tissue sections demonstrated that only mice harboring central nervous system (CNS) cells that expressed ecotropic MuLV were susceptible to ADPM. Our evidence indicates that the ecotropic MuLV RNA is transcribed in CNS cells from ecotropic MuLV proviruses that have been acquired by infection with exogenous ecotropic MuLV, probably during embryogenesis, the time when germ line proviruses in AKR and C58 mice first become activated. In young mice, MuLV RNA-containing cells were found exclusively in white-matter tracts and therefore were glial cells. An increase in the ADPM susceptibility of the mice with advancing age correlated with the presence of an increased number of ecotropic MuLV RNA-containing cells in the spinal cords which, in turn, correlated with an increase in the number of unmethylated proviruses in the DNA extracted from spinal cords. Studies with AKXD recombinant inbred strains showed that possession of a single replication-competent ecotropic MuLV provirus (emv-11) by Fv-1n/n mice was sufficient to result in ecotropic MuLV infection of CNS cells and ADPM susceptibility. In contrast, no ecotropic MuLV RNA-positive cells were present in the CNSs of mice carrying defective ecotropic MuLV proviruses (emv-3 or emv-13) or in which ecotropic MuLV replication was blocked by the Fv-1n/b or Fv-1b/b phenotype. Such mice were resistant to paralytic LDV infection. In utero infection of CE/J mice, which are devoid of any endogenous ecotropic MuLVs, with the infectious clone of emv-11 (AKR-623) resulted in the infection of CNS cells, and the mice became ADPM susceptible, whereas littermates that had not become infected with ecotropic MuLV remained ADPM resistant.

Animals↗
PubMed1995

Expression of ecotropic murine leukemia virus in the brains of C58/M, DBA2/J, and in utero-infected CE/J mice.

In C58 and AKR mice, endogenous N-tropic, ecotropic murine leukemia virus (MuLV) proviruses become activated in rare cells during embryogenesis. Resultant replication-competent progeny viruses then actively infect a large number of cells throughout the fetus, including cells in the developing central nervous system. By in situ hybridization analyses, we have assessed the presence of ecotropic MuLV RNA in the brains of C58 mice as a function of age. Only a few ecotropic MuLV-positive cells were observed in weanling mice, but the number of positive cells in the brain increased progressively with increasing age of the mice. Throughout the lives of the mice, the ecotropic MuLV RNA-positive cells were primarily located in well-defined white-matter tracts of the brain (commissura anterior, corpus callosum, fimbria hippocampi, optical tract, and striatum) and of the spinal cord. Cells of the subventricular zone also expressed ecotropic MuLV RNA, and in older mice a small number of positive cells were present in the grey matter. Infection of endogenous ecotropic MuLV provirus-less CE/J mice in utero with ecotropic MuLV clone AKR-623 resulted in the extensive infection of brain cells. The regional distribution of ecotropic MuLV RNA-containing cells was the same as observed in the brains of C58 mice, in which cells became infected by endogenously activated virus, but the number of positive cells was higher.

Aging↗
PubMed1995

Lactate dehydrogenase-elevating virus replication persists in liver, spleen, lymph node, and testis tissues and results in accumulation of viral RNA in germinal centers, concomitant with polyclonal activation of B cells.

Lactate dehydrogenase-elevating virus (LDV) replicates primarily and most likely solely in a subpopulation of macrophages in extraneuronal tissues. Infection of mice, regardless of age, with LDV leads to the rapid cytocidal replication of the virus in these cells, resulting in the release of large amounts of LDV into the circulation. The infection then progresses into life-long, asymptomatic, low-level viremic persistence, which is maintained by LDV replication in newly generated LDV-permissive cells which escapes all antiviral immune responses. In situ hybridization studies of tissue sections of adult FVB mice revealed that by 1 day postinfection (p.i.), LDV-infected cells were present in practically all tissues but were present in the highest numbers in the lymph nodes, spleen, and skin. In the central nervous system, LDV-infected cells were restricted to the leptomeninges. Most of the infected cells had disappeared at 3 days p.i., consistent with the cytocidal nature of the LDV infection, except for small numbers in lymph node, spleen, liver, and testis tissues. These tissues harbored infected cells until at least 90 days p.i. The results suggest that the generation of LDV-permissive cells during the persistent phase is restricted to these tissues. The continued presence of LDV-infected cells in testis tissue suggests the possibility of LDV release in semen and sexual transmission. Most striking was the accumulation of large amounts of LDV RNA in newly generated germinal centers of lymph nodes and the spleen. The LDV RNA was not associated with infected cells but was probably associated with virions or debris of infected, lysed cells. The appearance of LDV RNA in germinal centers in these mice coincided in time with the polyclonal activation of B cells, which leads to the accumulation of polyclonal immunoglobulin G2a and low-molecular-weight immune complexes in the circulation.

Animals↗
PubMed1995

C58 and AKR mice of all ages develop motor neuron disease after lactate dehydrogenase-elevating virus infection but only if antiviral immune responses are blocked by chemical or genetic means or as a result of old age.

Age-dependent poliomyelitis is a paralytic disease of C58 and AKR mice caused by cytocidal infection of anterior horn neurons with neuropathogenic strains of lactate dehydrogenase-elevating virus (LDV). The motor neurons are rendered LDV-permissive via an unknown mechanism through the expression of ecotropic murine leukemia virus (MuLV) in central nervous system (CNS) glial cells. Only old mice develop paralytic disease after LDV infection, but mice 5-6 months old or older can be rendered susceptible by suppression of anti-LDV immune responses by a single treatment with cyclophosphamide or X-irradiation before LDV infection. Younger mice appeared to be resistant in spite of this immunosuppresive treatment. The present results confirm that mice as young as 1 month of age possess CNS cells expressing ecotropic MuLV and show that these mice are susceptible to paralytic LDV infection provided their anti-LDV immune responses are blocked for an extended period of time by repeated cyclophosphamide treatments or by a genetic defect. Furthermore, old mice become naturally susceptible to paralytic LDV infection because of an impaired ability to mount a motor neuron protective anti-LDV immune response.

Aging↗
PubMed1994

Neonatal infection of mice with lactate dehydrogenase-elevating virus results in suppression of humoral antiviral immune response but does not alter the course of viraemia or the polyclonal activation of B cells and immune complex formation.

Neonatal infection of FVB mice with lactate dehydrogenase-elevating virus (LDV) prevented the normal formation of anti-LDV antibodies observed in mice infected at 5 days of age or older. Even 22 weeks post-infection, the concentration of circulating anti-LDV antibodies in neonatally infected mice was insignificant. However, the time course and level of persistent viraemia were the same in neonatally infected mice lacking anti-LDV antibodies as in mice infected at 5 or 15 days of age which developed normal antiviral immune responses. The results support the view that LDV replication in mice is unaffected by antiviral immune responses and instead is primarily dependent on the rate of regeneration of LDV-permissive macrophages. This view is further supported by the following findings. Treatment of mice with cyclophosphamide or dexamethasone, which are known to increase plasma LDV levels, increased the proportion of LDV-permissive macrophages in the peritoneum. Injection of mice with interleukin-3, which is known to stimulate macrophage development, increased plasma LDV levels in persistently infected mice 10- to 100-fold. During the first month of age when mice possess a higher proportion of LDV-permissive macrophages than older mice and peritoneal macrophages exhibit self-sustained growth, the persistent plasma LDV titres were also 10- to 100-fold higher than in older mice. The polyclonal activation of B cells induced by LDV that results in a permanent elevation of IgG2a or IgG2b in the circulation, and the formation of 180K to 300K immune complexes containing IgG2a or IgG2b were also the same in neonatally infected mice and mice infected 5 or 15 days after birth. Thus, the polyclonal activation of B cells occurs in the absence of an antiviral humoral immune response and the immune complexes do not contain anti-LDV antibodies. The immune complexes probably consist of autoantibodies formed in the course of the polyclonal activation of B cells and their cellular antigens.

Animals↗
PubMed1991

Efficacy of a Rift Valley fever virus vaccine against an aerosol infection in rats.

The formalin-inactivated Rift Valley fever virus (RVFV) vaccine, TSI-GSD-200, was administered subcutaneously to highly susceptible adult Wistar-Furth rats (LD50-1 p.f.u., ZH501 strain). Vaccine was administered on days 0, 7 and 28, the same time course used for at-risk personnel. Six months postimmunization, when the serum plaque-reduction neutralization titre (PRNT)80 had declined to low or undetectable levels, rats were challenged with 4.4 log10 p.f.u. of the virulent ZH501 strain in a nose-only dynamic aerosol apparatus. Ninety-seven per cent (33/34) of the non-vaccinated control rats died. In contrast, only 32% (33/105) of the vaccinated animals died. In vaccinated rats that succumbed, there was a doubling of the mean time to death and the cause of death shifted from hepatitis to encephalitis. Rats with a PRNT80 of greater than or equal to 1:40 were protected from clinical disease and histological evidence of hepatic or encephalitic lesions. While the precise mechanisms of immunity against aerosol challenge remain unresolved, here the serum PRNT titre correlated with protection.

Aerosols↗
PubMed1991

Infection of inbred rat strains with Rift Valley fever virus: development of a congenic resistant strain and observations on age-dependence of resistance.

A congenic rat strain (WF.LEW) was derived from the susceptible Wistar-Furth (WF) (background strain) and the resistant LEW (donor strain) inbred strains and was used to evaluate the phenotypic expression of a dominant Mendelian gene that confers resistance to fatal hepatic disease caused by the ZH501 strain of Rift Valley fever virus (RVFV). Resistance to hepatic disease developed gradually with age, with full expression at approximately 10 weeks in the WF.LEW and LEW rat strains. The ZH501 strain caused fatal hepatitis in WF rats regardless of age. However, resistance to the SA75 RVFV strain (relatively non-pathogenic for adult rats), was age- and dose-dependent in both WF and LEW rats. The resistance gene transferred to the newly derived WF.LEW congenic rat strain appears to amplify age-dependent resistance of adult rats, resulting in protection against fatal hepatic disease caused by the virulent ZH501 strain. The congenic rat strain will be a valuable asset in elucidating the mechanism of resistance to Rift Valley fever virus governed by the dominant Mendelian gene.

Aging↗
PubMed1990

Pathogenesis of a phleboviral infection (Punta Toro virus) in golden Syrian hamsters.

The hamster, Mesocricetus auratus, was examined as a possible model for investigating the poorly defined pathogenesis of the family Bunyaviridae, genus Phlebovirus. Punta Toro virus (PTV) isolates from Eastern Panama were highly virulent for two outbred and five inbred hamster strains, while isolates from western Panama were of low virulence. The Adames strain (eastern Panama) of PTV (LD50 approximately 1 PFU, sc) caused an acute fatal disease (average survival time, 3.8 days) in 10-week-old Lak: LVG (SYR) hamsters. Severe necrosis of the liver, spleen, and small intestine was associated with extensive expression of viral antigen in these organs. The Balliet strain (western Panama) of PTV (LD50 greater than 6 log10 PFU, subcutaneously) caused a mild hepatocellular infection with peak viral liver titers of 3-4 log10 PFU/g compared to 8-9 log10 PFU/g for the Adames strain. We observed histological lesions in the red pulp of the spleen or the lamina propria of the small intestine with the Adames strain. Lesions in the hamsters had characteristics of disseminated intravascular coagulation (DIC). The PTV-hamster model shares similarities to Rift Valley fever (phleboviral disease), which causes fatal disease in man and domesticated ruminants.

Animals↗
PubMed1988

The gerbil, Meriones unguiculatus, a model for Rift Valley fever viral encephalitis.

The gerbil, Meriones unguiculatus, was investigated as a model for the encephalitic form of Rift Valley fever. Resistance to necrotizing encephalitis was age-dependent with 100% mortality at 3 weeks, decreasing to approximately 20% by 10 weeks of age in outbred gerbils inoculated subcutaneously. Fatal encephalitis in the 10-week-old adults was dose-independent [1.0-7.0 log10 plaque forming units (PFU), subcutaneously]. Viral replication and histological lesions were followed serially throughout the course of the infection in young (4 week) and adult (10 week) gerbils. Viral replication was evident in the brain tissue of young gerbils from day 4 (3.0 log10 PFU/g) through day 7 (6.0 log10 PFU/g), the last day the young gerbils survived. Virus was only detected in the brain tissue of a single adult gerbil (day 7, 4.0 log10 PFU/g) of 26 studied in the sequential survey. In contrast, two moribund adult gerbils had approximately 7.0 log10 PFU/g of virus in the brain tissue on days 8 and 11. When young and adult gerbils were inoculated with a low dose (50 PFU) of virus intracranially, there were no detectable differences in the course of infection with all animals succumbing to fatal necrotizing encephalitis approximately 7 days postinoculation. The young gerbil becomes the first animal model in which uniformly fatal RVFV-induced encephalitis is produced without significant extraneural lesions.

Aging↗
PubMed1988

Bovine serum sialic acid: age-related changes in type and content.

1. The sialic acid content of newborn calf serum (4.8 mumol/ml) is approx. 3-fold higher than that of mature animals (1.4 mumol/ml) and decreases to 2.4 mumol/ml at 20 days of age. Colostrum-fed and colostrum-deprived calves have similar levels of sialic acid from birth to 14 days of age. 2. The high level of sialic acid in newborn calf serum is due predominantly to N-acetylneuraminic acid, since this sialic acid accounts for 93% of the total and since less than 5% of the sialic acid is O-acetylated. 3. Comparison of day 0 and day 20 serum by gel filtration and by SDS polyacrylamide gel electrophoresis demonstrates that the increase in sialic acid is associated with increased production and/or sialylation of components with MW of 45-60 kDa. 4. A high percentage (64%) of the sialic acid in newborn calf serum is detected with the lipid-linked sialic acid assay, relative to 20 day old (25%) or mature (18%) animals. 5. This indicates that the glycoproteins of newborn calf serum are more efficiently extracted under the conditions of this assay than glycoproteins of mature serum.

Age Factors↗
PubMed1988

Viral determinants of virulence for Rift Valley fever (RVF) in rats.

Rift Valley fever viral strains or variants (RVFV) were compared with respect to (a) virulence for Wistar-Furth rats; (b) in vitro sensitivity to rat and human interferon; (c) ability to form plaques in primary hepatocyte cultures from genetically resistant or susceptible rat strains, and (d) replicative potential in continuous rat cell lines. Egyptian strains were highly virulent for Wistar-Furth rats; relatively resistant to rat interferon-alpha/beta; capable of producing plaques in primary hepatocyte monolayers; and, in general, replicated more rapidly than the low-virulent, sub-Saharan strains. Virtually all strains from sub-Saharan Africa were sensitive to rat interferon and did not form plaques in rat hepatocyte monolayers. An exception was the 2269/74 strain from Zimbabwe, which had characteristics of the Egyptian strains including increased virulence for Wistar-Furth rats. The relative virulence of RVFV strains for rats did not correlate with interferon sensitivity when human recombinant interferon-alpha was tested on A-549 cells. Thus, several in vitro phenotypic characteristics of RVFV strains tend to correlate with virulence for Wistar-Furth rats and with geographical origin of the viral strains.

Animals↗
PubMed1988

Influence of protein intake and feeding strategy on reproductive performance of dairy cows.

A study was conducted to determine the impact of dietary CP concentration (13 vs. 20%) and feeding strategy (total mixed ration vs. separate feeding of the forage and concentrate) on reproductive performance of 57 early lactation dairy cows. Cows were assigned to one of four treatments in a 2 x 2 factorial arrangement. Rations composed of 40% forage (50% grass-legume silage:50% corn silage) and 60% concentrate (DM basis) were fed from d 5 to 100 postpartum. Cows fed a total mixed ration had lower ruminal ammonia and plasma urea N concentrations compared with cows fed separately. Feeding strategy groups showed no differences in reproductive performance. Cows fed a 20% CP ration had higher CP intake, higher ruminal ammonia, and higher urea N concentration in plasma and vaginal mucus. There were no differences between low and high CP groups in days to first observed estrus (24 vs. 27), days to first service (55 vs. 59), days open (72 vs 82) or services per conception (1.5 vs. 1.8). Days to first estimated ovulation were longer (22 vs. 17) in the high vs. low CP groups, and there was an interaction between protein intake and lactation number. Cows managed with an intensive program for detection of estrus and for reproductive health did not show differences in reproductive efficiency when fed 13 or 20% CP rations.

Animals↗
PubMed1987

Immunoelectron microscopy of Rift Valley fever viral morphogenesis in primary rat hepatocytes.

The morphogenesis of the hepatotropic phlebovirus Rift Valley fever virus (RVFV) has been examined by immuno-electron microscopy in primary hepatocyte cultures derived from genetically susceptible and resistant rat strains. RVFV replicates in both cell types with growth kinetics comparable with those seen in other permissive cells. However, in contrast to that has been observed in other cell types, RVFV replication in hepatocytes is associated with maturation at cellular surface membranes in addition to the smooth internal membranes of the Golgi and endoplasmic reticulum. Envelope acquisition at surface membranes occurred primarily on basolateral membranes. The events occurring in RVFV morphogenesis were indistinguishable in hepatocytes from resistant and susceptible animals; however, hepatocytes from susceptible animals produced significantly higher titers of virus.

Animals↗
PubMed1987

Pathogenesis of Rift Valley fever virus (RVFV) in inbred rats.

The pathogenesis of Rift Valley fever in adult rats from 3 inbred strains (LEW, MAXX, WF) was investigated. WF rats all died by day 2 postinoculation with viral tissue titers reaching 9 log10 PFU/g. LEW and MAXX rats were resistant to liver disease, but fatal necrotising encephalitis developed in 16 and 44% of the rats, respectively. Detection of serum neutralising antibody on day 3 coincided with clearance of virus from serum and liver, although infectious virus was detected in spleen homogenates as late as day 19 postinfection. Viral titers in LEW and MAXX rats did not exceed 4.5 log10 PFU/g. Cyclophosphamide immunosuppression of LEW rats led to death 5-9 days postinfection; early patterns of viral replication were not affected, but continued growth in the liver resulted in fatal hepatitis. These animals could be protected by passive antibody therapy administered on days 2-5 postinfection to mimic the serum neutralising antibody pattern seen in unmanipulated infected LEW rats. Thus, RVF virus replication and spread is rapid in the WF rats tissues, whereas in LEW and MAXX rats viral growth is less due to an intrinsic mechanism which allows sufficient time for an immune response to terminate infection. A slightly diminished immune response may lead to the development of encephalitis more frequently in MAXX than LEW rats. These rat strains should be useful in elucidating those mechanisms of resistance which limit RVFV-induced hepatitis and encephalitis.

Animals↗