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1.
Eur Respir J ; 37(5): 1037-42, 2011 May.
Article in English | MEDLINE | ID: mdl-20693244

ABSTRACT

A new and potentially more pathogenic group of human rhinovirus (HRV), group C (HRVC), has recently been discovered. We hypothesised that HRVC would be present in children with acute asthma and cause more severe attacks than other viruses or HRV groups. Children with acute asthma (n = 128; age 2-16 yrs) were recruited on presentation to an emergency department. Asthma exacerbation severity was assessed, and respiratory viruses and HRV strains were identified in a nasal aspirate. The majority of the children studied had moderate-to-severe asthma (85.2%) and 98.9% were admitted to hospital. HRV was detected in 87.5% and other respiratory viruses in 14.8% of children, most of whom also had HRV. HRVC was present in the majority of children with acute asthma (59.4%) and associated with more severe asthma. Children with HRVC (n = 76) had higher asthma severity scores than children whose HRV infection was HRVA or HRVB only (n = 34; p = 0.018), and all other children (n = 50; p = 0.016). Of the 19 children with a non-HRV virus, 13 had HRV co-infections, seven of these being HRVC. HRVC accounts for the majority of asthma attacks in children presenting to hospital and causes more severe attacks than previously known HRV groups and other viruses.


Subject(s)
Asthma/complications , Asthma/physiopathology , Picornaviridae Infections/complications , Rhinovirus/isolation & purification , Acute Disease , Adolescent , Asthma/epidemiology , Child , Child, Preschool , Disease Progression , Female , Humans , Male , Nasal Mucosa/metabolism , Nose/virology , Picornaviridae Infections/epidemiology , Rhinovirus/classification , Rhinovirus/genetics , Severity of Illness Index
2.
Arch Virol ; 152(6): 1201-8, 2007.
Article in English | MEDLINE | ID: mdl-17308978

ABSTRACT

A phylogenetic analysis of VP1 and VP4 nucleotide sequences of 52 recent CVA16 strains demonstrated two distinct CVA16 genogroups, A and B, with the prototype strain being the only member of genogroup A. CVA16 G-10, the prototype strain, showed a nucleotide difference of 27.7-30.2% and 19.9-25.2% in VP1 and VP4, respectively, in relation to other CVA16 strains, which formed two separate lineages in genogroup B with nucleotide variation of less than 13.4% and less than 16.3% in VP1 and VP4, respectively. Lineage 1 strains circulating before 2000 were later displaced by lineage 2 strains.


Subject(s)
Enterovirus A, Human/classification , Enterovirus A, Human/genetics , Evolution, Molecular , Phylogeny , Base Sequence , Capsid Proteins/genetics , DNA Primers/genetics , DNA, Viral/genetics , Enterovirus A, Human/isolation & purification , Hand, Foot and Mouth Disease/virology , Humans , Molecular Sequence Data , Viral Structural Proteins/genetics
3.
Arch Virol ; 151(5): 1003-13, 2006 May.
Article in English | MEDLINE | ID: mdl-16369861

ABSTRACT

Enterovirus 71 (EV71), first isolated in 1969, has been responsible for numerous outbreaks of hand, foot and mouth disease (HFMD) with a small proportion of cases associated with neurological disease. Since 1997 there has been a significant increase in both the prevalence and virulence of EV71 in the Asia-Pacific region. We have examined the genetic diversity of EV71 in a large Australian city (Sydney N.S.W.) over a nineteen-year period. We determined the VP1 gene sequence of forty-eight EV71 strains isolated between 1983 and 2001. Analysis by molecular phylogeny revealed the presence of four subgenogroups B2, B4, C1 and C2. The results indicate that the major lineage circulating in Sydney N.S.W. was subgenogroup C1 with a recent switch in dominance to B4 in 2000 and 2001.


Subject(s)
Enterovirus A, Human/classification , Enterovirus A, Human/genetics , Enterovirus Infections/epidemiology , Enterovirus Infections/virology , Australia/epidemiology , Enterovirus A, Human/isolation & purification , Hand, Foot and Mouth Disease/epidemiology , Hand, Foot and Mouth Disease/virology , Humans , Molecular Epidemiology , Molecular Sequence Data , Phylogeny , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Urban Population , Viral Structural Proteins/chemistry , Viral Structural Proteins/genetics
4.
J Gen Virol ; 84(Pt 7): 1723-1728, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12810865

ABSTRACT

Enhancement of flavivirus infection in vitro in the presence of subneutralizing concentrations of homologous or heterologous antiserum has been well described. However, the importance of this phenomenon in the enhancement of flavivirus infection in vivo has not been established. In order to study antibody-mediated enhancement of flavivirus infection in vivo, we investigated the effect of passive immunization of mice with Japanese encephalitis virus (JE) antiserum on the outcome of infection with Murray Valley encephalitis virus (MVE). We show that prior treatment of mice with subneutralizing concentrations of heterologous JE antiserum resulted in an increase in viraemia titres and in mortality following challenge with wild-type MVE. Our findings support the hypothesis that subneutralizing concentrations of antibody may enhance flavivirus infection and virulence in vivo. These findings are of potential importance for the design of JE vaccination programs in geographic areas in which MVE co-circulates. Should subneutralizing concentrations of antibody remain in the population following JE vaccination, it is possible that enhanced disease may be observed during MVE epidemics.


Subject(s)
Antibodies, Viral/immunology , Antibody-Dependent Enhancement , Encephalitis Virus, Murray Valley/pathogenicity , Encephalitis, Arbovirus/mortality , Immunization, Passive , Japanese Encephalitis Vaccines/administration & dosage , Animals , Antibodies, Viral/administration & dosage , Antibodies, Viral/blood , Brain/virology , Encephalitis Virus, Japanese/immunology , Encephalitis Virus, Murray Valley/immunology , Encephalitis, Arbovirus/virology , Encephalitis, Japanese/prevention & control , Japanese Encephalitis Vaccines/immunology , Mice , Mice, Inbred BALB C , Vaccination , Viremia/mortality , Viremia/virology , Virulence , Virus Replication
5.
Arch Virol ; 148(7): 1369-85, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12827466

ABSTRACT

Human enterovirus 71 (EV71) (genus Enterovirus, family Picornaviridae) has been responsible for sporadic cases and outbreaks of hand-foot-and-mouth disease (HFMD), aseptic meningitis, encephalitis and poliomyelitis-like disease in Europe, the U.S.A., Australia and Asia. Recently, there has been an increase in EV71 activity in the Asia-Pacific region, with many outbreaks of HFMD associated with brainstem encephalitis manifesting as neurogenic pulmonary oedema with a high case fatality rate. In 1997, and again in 2000, EV71 outbreaks occurred in peninsular Malaysia. Variations in VP1 gene sequences have been shown to divide all known EV71 field isolates into three distinct genogroups (A, B and C). Consequently we examined the VP1 gene sequences of 43 EV71 strains isolated in peninsular Malaysia between 1997 and 2000 in order to determine the genogroup prevalence over the period. In this study we show that four subgenogroups (B3, B4, C1 and C2) of EV71 circulated in peninsular Malaysia between 1997 and 2000. Subgenogroups B3, B4 and C1 have been identified as the primary cause of the outbreaks of EV71 in peninsular Malaysia. Subgenogroup C1 also displayed endemic circulation from 1997 to 2000 and subgenogroup C2 was present at a low level during the 1997 outbreak.


Subject(s)
Enterovirus Infections/epidemiology , Enterovirus/genetics , Hand, Foot and Mouth Disease/epidemiology , Amino Acid Sequence , Base Sequence , Consensus Sequence , DNA Primers , Disease Outbreaks , Enterovirus/classification , Enterovirus/pathogenicity , Genotype , Geography , Hand, Foot and Mouth Disease/mortality , Humans , Incidence , Malaysia/epidemiology , Molecular Epidemiology/methods , Phylogeny , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment
6.
Arch Virol ; 147(6): 1155-72, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12111426

ABSTRACT

We report on the development and characterisation of a recombinant Murray Valley encephalitis virus (MVE) envelope glycoprotein expression system that results in the secretion of subviral particles (SVPs) upon transfection of the murine fibroblast (COS-7) cell line. Initially, aspects of the physical and antigenic structure of cell-associated and secreted forms of the MVE envelope glycoproteins (prM and E) are presented. We then show that BALB/c mice inoculated with SVPs purified from pcDNA(3)-prM/E-transfected COS-7 cell supernatants are protected from lethal challenge with the virulent prototype strain MVE-1-51 and that this protection correlates with the development of a neutralising humoral immune response by the host. By contrast, prior immunisation with cell-associated, recombinant MVE envelope glycoproteins did not protect mice from challenge with MVE-1-51 and this was associated with the development of antibody that was unable to neutralise virus infectivity in vitro. These studies demonstrate that SVPs derived from the in vitro expression of recombinant MVE prM and E genes are an effective candidate vaccine for the prevention of encephalitis in the mouse model.


Subject(s)
Encephalitis Virus, Murray Valley/immunology , Encephalitis, Arbovirus/prevention & control , Recombination, Genetic , Viral Envelope Proteins/immunology , Viral Vaccines/immunology , Virion/immunology , Animals , Antibodies, Viral/blood , COS Cells , Cell Line , Chlorocebus aethiops , Encephalitis Virus, Murray Valley/genetics , Encephalitis Virus, Murray Valley/pathogenicity , Encephalitis, Arbovirus/immunology , Mice , Mice, Inbred BALB C , Neutralization Tests , Transfection , Vero Cells , Viral Envelope Proteins/genetics , Viral Envelope Proteins/metabolism , Virion/genetics , Virion/physiology , Virulence
7.
J Gen Virol ; 82(Pt 11): 2629-2639, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11602774

ABSTRACT

The complete nucleotide sequences are reported of two strains of echovirus 7, the prototype Wallace strain (Eo7-Wallace) and a recent Malaysian strain isolated from the cerebrospinal fluid of a child with fatal encephalomyelitis (Eo7-UMMC strain). The molecular findings corroborate the serological placement of the UMMC strain as echovirus 7. Both Eo7-Wallace and Eo7-UMMC belong to the species human enterovirus B and are most closely related to echovirus 11. Eo7-UMMC has undergone significant genetic drift from the prototype strain in the 47 years that separate the isolation of the two viruses. Phylogenetic analysis revealed that Eo7-UMMC did not arise from recombination with another enterovirus serotype. The molecular basis for the severely neurovirulent phenotype of Eo7-UMMC remains unknown. However, it is shown that mutations in the nucleotide sequence of the 5' untranslated region (UTR) of Eo7-UMMC result in changes to the putative structure of the 5' UTR. It is possible that these changes contribute to the neurovirulence of Eo7-UMMC.


Subject(s)
Encephalitis, Viral/virology , Enterovirus B, Human/genetics , Enterovirus Infections/virology , Gene Frequency , Genome, Viral , 3' Untranslated Regions/chemistry , 5' Untranslated Regions/chemistry , Amino Acid Sequence , Base Sequence , Cerebrospinal Fluid/virology , Child, Preschool , Enterovirus B, Human/chemistry , Enterovirus B, Human/classification , Humans , Male , Molecular Sequence Data , Nucleic Acid Conformation , Phylogeny , Sequence Analysis, DNA
8.
J Virol ; 75(16): 7692-702, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11462041

ABSTRACT

Molecular determinants of virulence in flaviviruses cluster in two regions on the three-dimensional structure of the envelope (E) protein; the base of domain II, believed to serve as a hinge during pH-dependent conformational change in the endosome, and the lateral face of domain III, which contains an integrin-binding motif Arg-Gly-Asp (RGD) in mosquito-borne flaviviruses and is believed to form the receptor-binding site of the protein. In an effort to better understand the nature of attenuation caused by mutations in these two regions, a full-length infectious cDNA clone of Murray Valley encephalitis virus prototype strain 1-51 (MVE-1-51) was employed to produce a panel of site-directed mutants with substitutions at amino acid positions 277 (E-277; hinge region) or 390 (E-390; RGD motif). Viruses with mutations at E-277 (Ser-->Ile, Ser-->Asn, Ser-->Val, and Ser-->Pro) showed various levels of in vitro and in vivo attenuation dependent on the level of hydrophobicity of the substituted amino acid. Altered hemagglutination activity observed for these viruses suggests that mutations in the hinge region may indirectly disrupt the receptor-ligand interaction, possibly by causing premature release of the virion from the endosomal membrane prior to fusion. Similarly, viruses with mutations at E-390 (Asp-->Asn, Asp-->Glu, and Asp-->Tyr) were also attenuated in vitro and in vivo; however, the absorption and penetration rates of these viruses were similar to those of wild-type virus. This, coupled with the fact that E-390 mutant viruses were only moderately inhibited by soluble heparin, suggests that RGD-dependent integrin binding is not essential for entry of MVE and that multiple and/or alternate receptors may be involved in cell entry.


Subject(s)
Encephalitis Virus, Murray Valley/genetics , Viral Envelope Proteins/genetics , Animals , Binding Sites/genetics , Chlorocebus aethiops , Encephalitis, Arbovirus/virology , Mutagenesis, Site-Directed , Mutation , Receptors, Virus/physiology , Vero Cells , Virus Replication/genetics
9.
Pathology ; 32(1): 49-51, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10740807

ABSTRACT

A 4-year-old aboriginal boy developed encephalitis due to Murray Valley encephalitis virus (MVE) following an earlier infection with Kunjin virus (KUN). The illness was severe, resulting in cerebral atrophy and profound physical and intellectual disability. The earlier KUN infection complicated his serological profile and delayed antibody responses to MVE. By contrast, the reverse transcriptase-polymerase chain reaction (RT-PCR) assay detected MVE in serum 3 days after the onset of illness and 4 days before the appearance of MVE-specific IgM. We suggest that MVE-specific RT-PCR provides rapid and specific diagnosis of MVE and should be used more widely for the diagnosis of acute viral encephalitis in cases originating from flavivirus endemic areas.


Subject(s)
Encephalitis Virus, Murray Valley/genetics , Encephalitis, Arbovirus/diagnosis , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction , Antibodies, Viral/analysis , Child, Preschool , Encephalitis Virus, Murray Valley/immunology , Encephalitis Virus, Murray Valley/isolation & purification , Encephalitis, Arbovirus/blood , Encephalitis, Arbovirus/cerebrospinal fluid , Humans , Immunoglobulin M/analysis , Male , Western Australia
10.
J Virol ; 73(10): 8781-90, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10482632

ABSTRACT

A study of immunopathology in the central nervous system (CNS) during infection with a virulent strain of Murray Valley encephalitis virus (MVE) in weanling Swiss mice following peripheral inoculation is presented. It has previously been shown that virus enters the murine CNS 4 days after peripheral inoculation, spreads to the anterior olfactory nucleus, the pyriform cortex, and the hippocampal formation at 5 days postinfection (p.i.), and then spreads throughout the cerebral cortex, caudate putamen, thalamus, and brain stem between 6 and 9 days p.i. (P. C. McMinn, L. Dalgarno, and R. C. Weir, Virology 220:414-423, 1996). Here we show that the encephalitis which develops in MVE-infected mice from 5 days p.i. is associated with the development of a neutrophil inflammatory response in perivascular regions and in the CNS parenchyma. Infiltration of neutrophils into the CNS was preceded by increased expression of tumor necrosis factor alpha and the neutrophil-attracting chemokine N51/KC within the CNS. Depletion of neutrophils with a cytotoxic monoclonal antibody (RB6-8C5) resulted in prolonged survival and decreased mortality in MVE-infected mice. In addition, neutrophil infiltration and disease onset correlated with expression of the enzyme-inducible nitric oxide synthase (iNOS) within the CNS. Inhibition of iNOS by aminoguanidine resulted in prolonged survival and decreased mortality in MVE-infected mice. This study provides strong support for the hypothesis that Murray Valley encephalitis is primarily an immunopathological disease.


Subject(s)
Central Nervous System/virology , Encephalitis Virus, Murray Valley , Encephalitis, Arbovirus/metabolism , Neutrophil Activation , Nitric Oxide Synthase/metabolism , Animals , Central Nervous System/immunology , Central Nervous System/metabolism , Encephalitis, Arbovirus/immunology , Mice , Nitric Oxide Synthase Type II
12.
J Gen Virol ; 77 ( Pt 9): 2085-8, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8811007

ABSTRACT

A neutralization escape variant of Murray Valley encephalitis virus (MVE), of low neuroinvasiveness in mice and with low haemagglutination activity, had a reduced rate of replication in cultured cells during the early phase of infection compared to wild-type MVE. The variant was internalized by Vero cells at a similar rate to wild-type MVE at pH 7.4, but had reduced pH-dependent membrane fusion activity. In fusion-from-within experiments in infected mosquito (C6/36) cells, the variant had a lowered pH threshold for induction of fusion, which occurred at a reduced rate and to a lesser extent than for wild-type virus. Fusion was inhibited by monoclonal antibodies specific for envelope protein epitopes E-5 and E-8, which were implicated as determinants of fusion. These observations are discussed in relation to the regulation of MVE replication by fusion of the viral envelope with endosome membranes and, in turn, how rates of replication may affect neuroinvasion.


Subject(s)
Encephalitis Virus, Murray Valley/genetics , Membrane Fusion , Viral Envelope Proteins/genetics , Aedes/cytology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , Cell Line , Chlorocebus aethiops , Encephalitis Virus, Murray Valley/pathogenicity , Encephalitis Virus, Murray Valley/physiology , Genetic Variation , Mice , Vero Cells , Virus Replication
13.
Virology ; 220(2): 414-23, 1996 Jun 15.
Article in English | MEDLINE | ID: mdl-8661392

ABSTRACT

A Murray Valley encephalitis virus (MVE) field isolate of high neuroinvasiveness (BH3479) and a neutralization escape variant of low neuroinvasiveness (BHv1) selected from BH3479 (which differ by a single amino acid at residue 277 in the envelope glycoprotein) were examined for their distribution in the tissues of weanling Swiss mice at various times after footpad inoculation. BH3479 was first detected in lymph nodes draining the inoculated limb at 24 hr postinoculation (pi) and was found in serum between 36 and 72 hr pi. BH3479 was first detected in the central nervous system (CNS) at 4 days pi and reached maximum CNS titers ( > 10(9) PFU/g) between 6 and 9 days pi. All BH3479-infected mice developed encephalitis and died before 10 days pi. In contrast, BHv1 was not detected in lymph nodes draining the footpad at any time after inoculation; BHv1 was first detected in the serum between 60 and 72 hr pi-24 hr later, and at a 20-fold lower titer than for BH3479. BHv1 was first detected in the CNS at 7 days pi 3 days later and at a 300-fold lower titer than for BH3479. After 10 days pi, BHv1 could not be isolated from the CNS or from other host tissues. Most BHv1-infected mice experienced a subclinical infection; the mortality rate from BHv1 infection was less than 1%. Both viruses appeared to enter the CNS via the olfactory lobes. BH3479 spread throughout the CNS in a rostral to caudal direction over 3-4 days. In contrast, BHv1 infection in the CNS was restricted to the olfactory lobes and adjacent structures of the forebrain.


Subject(s)
Encephalitis Virus, Murray Valley/pathogenicity , Encephalitis, Arbovirus/virology , Animals , Antibodies, Viral/blood , Brain/virology , Chlorocebus aethiops , Culex/virology , Injections, Intraperitoneal , Mice , Neurons/virology , RNA, Viral/metabolism , Vero Cells
14.
Virology ; 211(1): 10-20, 1995 Aug 01.
Article in English | MEDLINE | ID: mdl-7645203

ABSTRACT

Neutralization escape variants of Murray Valley encephalitis virus were selected using a type-specific, neutralizing, and passively protective anti-envelope protein (E) monoclonal antibody (4B6C-2) which defines epitope E-1c. Nucleotide sequence analysis revealed single nucleotide changes in the E genes of 15 variants resulting in nonconservative amino acid substitutions in all cases. One variant had a three-nucleotide deletion in the E gene which resulted in loss of serine at residue 277. Changes were clustered into two separate regions of the E polypeptide (residues 126-128 and 274-277), indicating that E-1c is a discontinuous epitope. One variant (BHv1), altered at residue 277 (Ser-->Ile), failed to hemagglutinate across the pH range 5.5-7.5, in contrast to parental virus and the other escape variants which hemagglutinated at an optimal pH of 6.6. BHv1 was also of reduced neuroinvasiveness in 21-day-old mice following intraperitoneal inoculation compared to the other viruses. Parental virus and the neutralization escape variants grew equally well in both vertebrate and invertebrate cell cultures, indicating that the reduced neuroinvasiveness of BHv1 was not due to a major abnormality of replication.


Subject(s)
Brain/virology , Encephalitis Virus, Murray Valley/physiology , Encephalitis Virus, Murray Valley/pathogenicity , Encephalitis, Arbovirus/pathology , Genetic Variation , Hemagglutinins, Viral/biosynthesis , Point Mutation , Amino Acid Sequence , Animals , Base Sequence , Brain/pathology , Chlorocebus aethiops , Codon/genetics , Encephalitis Virus, Murray Valley/genetics , Encephalitis, Arbovirus/virology , Enzyme-Linked Immunosorbent Assay , Erythrocytes/immunology , Geese , Hemagglutination Tests , Mice , Sequence Deletion , Vero Cells , Viral Plaque Assay , Virulence , Virus Replication
15.
J Gen Virol ; 76 ( Pt 4): 865-72, 1995 Apr.
Article in English | MEDLINE | ID: mdl-9049332

ABSTRACT

Variants of the prototype Murray Valley encephalitis virus (MVE-1-51) were selected by serial plaque purification and amplification in monkey kidney (Vero) cells. Four clones (C1-C4) at passage levels two and nine (P2 and P9) were examined in 21-day-old Swiss outbred mice for neuroinvasiveness (assessed from LD50 values after intraperitoneal inoculation) and neurovirulence (LD50 values after intracranial inoculation). The growth characteristics of the clones were determined in intracranially inoculated mouse brain and in mouse neuroblastoma, Vero and mosquito (C6/36) cell lines. Genomic RNA of the cloned virus stocks was sequenced through the structural protein genes (E, prM/M and C) and the 5' untranslated region. Clone C2P2 was of high neuroinvasiveness whereas C2P9 was of low neuroinvasiveness; there were also decreased yields of C2P9 in C6/36 cells compared to C2P2 and MVE-1-51. These changes were associated with the substitution of valine for phenylalanine at amino acid position 141 of the C2P9 E protein. Clone C4P2 was of high neurovirulence and low neuroinvasiveness; C4P9 was of low neurovirulence, a change accompanied by a further reduction in neuroinvasiveness. Concomitantly, C4P9 showed a pronounced reduction in growth rates and yields in 21-day-old Swiss mouse brain, in mouse neuroblastoma cells and in C6/36 cells compared to parental virus. The phenotypic changes in clone 4 appear to be due to mutation(s) within non-structural protein genes.


Subject(s)
Encephalitis Virus, Murray Valley/pathogenicity , Encephalitis, Arbovirus/virology , Aedes/cytology , Animals , Brain/virology , Cell Fusion , Cell Line , Chlorocebus aethiops , Encephalitis Virus, Murray Valley/isolation & purification , Hemagglutination , Hydrogen-Ion Concentration , Mice , Mutagenesis , Sequence Analysis, DNA , Tumor Cells, Cultured , Vero Cells , Virulence
16.
J Infect Dis ; 164(6): 1113-8, 1991 Dec.
Article in English | MEDLINE | ID: mdl-1955711

ABSTRACT

A large outbreak of epidemic keratoconjunctivitis occurred in Alice Springs, Australia, between July and September 1989. Initially, there was a large outbreak within two child care centers, followed by a more prolonged outbreak within the community. A simultaneous outbreak occurred among staff at the local hospital. Infected children developed mild conjunctivitis, whereas adults developed typical keratoconjunctivitis. Conjunctival swabs from 30 cases were cultured and adenovirus was recovered from 18, all of which were typed by neutralization assay as adenovirus type 8. DNA restriction fragment analysis of the genomes of 5 isolates revealed they were identical, distinct from prototype adenovirus type 8, and nearly identical to adenovirus genome type 8C (Ad-8C), which was previously reported in the southern United States in the early 1970s. Ad-8C was present in another region of Australia greater than or equal to 1 year before the epidemic.


Subject(s)
Adenovirus Infections, Human/epidemiology , Cross Infection/epidemiology , Disease Outbreaks , Keratoconjunctivitis/epidemiology , Occupational Diseases/epidemiology , Adenovirus Infections, Human/microbiology , Adenoviruses, Human/classification , Adenoviruses, Human/genetics , Adenoviruses, Human/isolation & purification , Adult , Blotting, Southern , Child , Child, Preschool , Conjunctiva/microbiology , Cross Infection/microbiology , DNA, Viral/analysis , Disease Susceptibility , Humans , Infant , Keratoconjunctivitis/microbiology , Neutralization Tests , Northern Territory/epidemiology , Nurses , Occupational Diseases/microbiology , Restriction Mapping , Students, Medical
17.
Pathology ; 23(1): 39-44, 1991 Jan.
Article in English | MEDLINE | ID: mdl-1712093

ABSTRACT

Langerhans cells (LC) are dendritic antigen presenting cells of bone marrow origin which reside in the suprabasal layer of the epidermis. They express high concentrations of Class II MHC glycoproteins on their plasma membrane and transport cutaneous antigen to local lymph nodes for presentation to helper T cells. They are thus essential for the induction of cutaneous immunity. Gliotoxin is a member of the epipolythiodioxopiperazine (ETP) group of fungal metabolites, derived from the human pathogen Aspergillus fumigatus. It has been shown to have immunomodulating properties in vivo and in vitro, and has been proposed as a potential immunosuppressant for transplantation therapy. Epicutaneous application of gliotoxin reduced the numbers of epidermal LC by 30-35 per cent with an associated morphological change from highly dendritic to a more rounded form. Electron microscopic studies showed selective damage to LC at very low (nM) concentrations of gliotoxin, with no obvious effect on adjacent keratinocytes. LC numbers remained depleted for 13 weeks after initial treatment, suggesting that systemic suppression or prolonged retention of gliotoxin within the skin may play a role in its mechanism of action.


Subject(s)
Epidermis/pathology , Gliotoxin/pharmacology , Langerhans Cells/pathology , Animals , Cell Count/drug effects , Epidermis/ultrastructure , Female , Male , Mice , Mice, Inbred BALB C , Microscopy, Electron , Time Factors
18.
Immunology ; 71(1): 46-51, 1990 Sep.
Article in English | MEDLINE | ID: mdl-1698716

ABSTRACT

Dendritic Langerhans' cells (LC), which are essential for the induction of cutaneous immunity, express high concentrations of class II major histocompatibility (MHC) glycoproteins (Ia in the mouse) on their plasma membrane. Application of gliotoxin, a member of the epipolythiodoxopiperazine (ETP) group of fungal metabolites, reduces epidermal LC density and alters their morphology from highly dendritic to a more rounded form. Here we demonstrate that gliotoxin also alters LC function, reducing contact hypersensitivity (CHS) responses due to the development of suppressor cells, and enhancing C57BL tail skin graft survival on BALB/c recipients. The reduction in LC density following gliotoxin application was shown to enhance skin graft survival, by reducing the concentration of Ia antigens within the graft, by using congenic mouse strains: B10.A(2R) x B10.A, differing only at H-2D, and B10.A(2R) x B10.A(4R), differing only at H-2 I-E. Treatment of B10.A(2R) tail skin with gliotoxin for 1 week did not affect its survival when grafted onto H-2D-disparate B10.A mice, whereas, when grafted onto H-2 I-E-disparate B10.A(4R) hosts, the grafts were not only accepted permanently, but induced specific unresponsiveness. It is concluded that gliotoxin has a marked effect on LC function, inhibiting CHS responses by the induction of suppressor cells and prolonging graft survival between H-2-disparate and congenic mouse strains.


Subject(s)
Dermatitis, Contact/immunology , Gliotoxin/pharmacology , Graft Survival/immunology , Langerhans Cells/immunology , Skin Transplantation/immunology , Animals , Cell Count , Dinitrofluorobenzene/immunology , H-2 Antigens/analysis , Lymphocyte Activation , Mice , Mice, Inbred Strains , T-Lymphocytes, Regulatory/immunology
20.
Med J Aust ; 151(10): 588-90, 592, 594, 1989 Nov 20.
Article in English | MEDLINE | ID: mdl-2687652

ABSTRACT

A young, previously healthy woman developed bilateral exudative tonsillitis that was associated with severe systemic symptoms. This was followed by evidence of multisystem disease with acute abdominal pain, raised liver enzyme levels, respiratory difficulty, increasing drowsiness and multiple vesicular skin lesions. Herpes simplex virus type-1 was isolated from skin lesions and a throat swab and herpes simplex virus type-1 antigen was detected in a liver biopsy sample. She recovered rapidly without any sequelae after treatment with intravenously administered acyclovir.


Subject(s)
Herpes Simplex/immunology , Abdominal Pain/etiology , Acyclovir/therapeutic use , Adult , Female , Hepatitis, Viral, Human/etiology , Hepatitis, Viral, Human/microbiology , Hepatitis, Viral, Human/pathology , Herpes Simplex/complications , Herpes Simplex/drug therapy , Herpes Simplex/pathology , Humans , Immune Tolerance
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