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Biomedical subjects

J S Mackenzie

Publications and source records attributed to J S Mackenzie.

At least 55 records · Page 3Linked to original sources
PubMed1998

A comparison of the diseases caused by Ross River virus and Barmah Forest virus.

Barmah Forest virus (BFV) and Ross River virus (RRV) are mosquito-borne viruses with similar vectors and environmental requirements. They cause diseases characterised by arthralgia, arthritis and myalgia, often accompanied by fever and rash. Arthritis is more common and more prominent in RRV disease and rash is more common and florid with BFV infection, although the diseases cannot be reliably distinguished by their clinical symptoms. Diagnosis is based on serological tests and a definite diagnosis of recent infection requires the demonstration of rising titres of IgG. Arthralgia, myalgia and lethargy may continue for at least six months in up to half of patients with RRV, but in only about 10% of patients with BFV. Both diseases are managed symptomatically.

Alphavirus↗
PubMed1998

Arboviruses in the Australian region, 1990 to 1998.

Arboviruses continue to be major human pathogens in the Australian region. This report provides a summary of the activities of these viruses over the past eight years, and comments on new findings relevant to their respective ecologies. Of particular interest and concern is the propensity of these viruses to spread. The examples discussed include the initiation of dengue epidemics in north Queensland by virus imported in viraemic travellers; the spread of Japanese encephalitis virus to the Australasian region and its probable enzootic establishment in the south-west of Papua New Guinea; the potential spread of Ross River virus to other countries, as demonstrated by the 1979-80 outbreak in the South Pacific, and the recent occurrence in military personnel from the United States of America after an exercise; and the recent spread of Barmah Forest virus into Western Australia.

Animals↗
PubMed1998

Transient hypoadrenalism during surgical critical illness.

OBJECTIVE: To report the cortisol levels in 6 patients during and after severe inflammation. DESIGN: Patients with severe inflammatory disease had basal and stimulated (cosyntropin) serum cortisol levels determined at the time of severe and less severe inflammation. SETTING: Intensive care unit and wards of a tertiary care center. PATIENTS: Six patients with continued evidence of severe inflammation, despite aggressive management of the underlying inflammatory disease. INTERVENTIONS: Five of 6 patients received hydrocortisone at "physiologic" doses. MAIN OUTCOME MEASURES: Basal and stimulated serum cortisol levels. RESULTS: The mean+/-SD cortisol data for these patients were as follows: baseline cortisol level during inflammation, 350+/-121 nmol/L (n=6); stimulated cortisol level during inflammation, 571+/-326 nmol/L (n=6); baseline cortisol level with less inflammation, 833+/-339 nmol/L (P=.03 vs baseline level during inflammation) (n=5); and stimulated cortisol level with less inflammation, 1090+/-295 nmol/L (P=.03 vs stimulated level during inflammation) (n=4). Manifestations of inflammation decreased with hydrocortisone administration. CONCLUSIONS: Severe inflammation may result in lower-than-expected serum cortisol levels, which then increase significantly as the inflammation decreases. Transient hypoadrenalism may aggravate the adverse effects of severe inflammation. These effects may be ameliorated by administering physiologic rather than pharmacologic doses of hydrocortisone.

Adrenal Insufficiency↗
PubMed1998

Genetically determined resistance to flavivirus infection in wild Mus musculus domesticus and other taxonomic groups in the genus Mus.

Inherited resistance to flaviviruses in laboratory mice is a rare trait conferred by an autosomal dominant gene (Flvr). To provide information on genetic resistance to flaviviruses in wild mice, we analysed (i) wild M. m. domesticus trapped in Australia, and (ii) mice representing other species and subspecies in the genus Mus. Mice were screened for resistance relative to C3H/HeJ mice by intracerebral challenge with Murray Valley encephalitis virus or yellow fever virus, and breeding studies were undertaken to identify inherited resistance factors. Widespread flavivirus resistance was demonstrated in Australian M. m. domesticus. A single, autosomal dominant Flvr-like gene appeared to be primarily responsible, but there was some evidence for additional inherited resistance factors. Flavivirus resistance was also identified in other taxonomic groups, and a genetic basis for this resistance was demonstrated in M. m. musculus (Skive), M. spretus, and M. spicilegus. Interestingly, M. m. musculus (CZI-O) were more susceptible than C3H/HeJ mice. Our findings show that genetic resistance to flaviviruses is common in divergent taxonomic groups in the genus Mus, suggesting that the trait has an ancient evolutionary origin, but whether flavivirus resistance genes have an anti-viral role or serve some other function is unknown.

Animals↗
PubMed1998

Identification of Australian arboviruses in inoculated cell cultures using monoclonal antibodies in ELISA.

An ELISA using a panel of specific monoclonal antibodies was developed to identify all alpha and flaviviruses isolated from mosquitoes caught throughout Australia. This technique is sensitive and rapid and is more specific than the traditional methods used to identify flaviviruses. The ability to identify unknown virus isolates from field-caught mosquitoes quickly and accurately improves the efficiency of arbovirus surveillance programs and allows health authorities to give an early warning of an increased health risk from a mosquito-borne virus in a particular region.

Aedes↗
PubMed1998

Characterization of defective viral RNA produced during persistent infection of Vero cells with Murray Valley encephalitis virus.

Defective interfering viral particles are readily produced in cell culture after a high multiplicity of infection with many animal RNA viruses. Due to defects that they carry in their genomes, their life cycle needs to be complemented by the helper functions provided by a parental virus which makes them both dependent on and competitive with the parental virus. In many instances, this may cause the abrogation of a lytic cycle of the parental virus, leading to a persistent infection. In this paper, we describe for the first time the presence of truncated or defective interfering viral RNAs produced in Vero cells persistently infected with the flavivirus Murray Valley encephalitis virus. While these RNAs have not been detected in acutely infected Vero cells, their appearance coincided with the establishment of persistent infection. We also show for the first time that the defective viral RNAs replicate well in both cell culture and cell-free virus replication systems, indicating that they may interfere with the replication of parental virus at the level of viral RNA synthesis. Significantly, structural analyses of these RNA species including nucleotide sequencing have revealed that they carry similar nucleotide deletions encompassing the genes coding for the prM and E proteins and various gene segments coding for the N terminus of the NS1 protein. These deletions are in frame, allowing the synthesis of truncated NS1 proteins to occur in persistently infected cells. This may have further implications for the interference with the parental virus at the level of viral RNA synthesis in addition to a major one at the level of virion assembly and release.

Animals↗
PubMed1997

Molecular characterization of virus-specific RNA produced in the brains of flavivirus-susceptible and -resistant mice after challenge with Murray Valley encephalitis virus.

Natural resistance to flaviviruses in mice is controlled by a single genetic locus, FIv, on chromosome 5. Although the mechanism of this resistance is not fully understood, it is believed to operate at the level of virus replication rather than the immune response. It has been hypothesized that enhanced production of viral defective interfering (DI) particles is responsible for a substantial reduction in the titres of infectious virus in resistant mice. However, this has never been established at the molecular level since such particles have not been isolated and characterized. We have studied the products of virus replication in the brains of flavivirus-susceptible C3H/HeJ (Flv(s)) and -resistant congenic C3H/RV (Flv(r)) mice after an intracerebral challenge (i.c.) with Murray Valley encephalitis (MVE) virus and have found no evidence for the accumulation of truncated viral RNA in the brains of resistant mice. All three major viral RNA species, the replicative intermediate (RI), replicative form (RF) and virion RNA (vRNA) together with a subgenomic RNA species of 0.6 kb, which has not been previously described, were present in the brains of both mouse strains. However, the viral RF and RI RNA forms preferentially accumulated in the brains of resistant mice. Thus, we confirm that the resistance allele Flv(r) interferes with discrete steps in flavivirus replication, although the precise mechanism remains to be determined.

Animals↗
PubMed1997

Genetic stability among temporally and geographically diverse isolates of Barmah Forest virus.

An increase in the incidence of polyarthritis caused by Barmah Forest (BF) virus, and its recent emergence into Western Australia, prompted a study of the molecular epidemiology of this Australian mosquito-borne alphavirus. The nucleotide sequence of a 500-basepair region of the 3' end of the envelope (E2) gene of the prototype BF virus strain (BH2193) was compared with other members of the alphavirus genus, and to a panel of isolates of BF virus collected more for than 20 years from different geographic regions of Australia. The BF virus was shown to be genetically distinct from other members of the alphavirus genus. A high degree of sequence homology (98-100%) was found between the BF isolates, with no evidence of geographic or temporal divergence. This nucleotide homogeneity was similar to that observed with other Australian mosquito-borne viruses with avian vertebrate hosts, such as Sindbis, Murray Valley, and Kunjin viruses, but it contrasts to the heterogeneity reported for Ross River virus, an alphavirus with mammalian vertebrate hosts.

Alphavirus↗
PubMed1997

Investigation of gray-headed flying foxes (Pteropus poliocephalus) (Megachiroptera: Pteropodidae) and mosquitoes in the ecology of Ross River virus in Australia.

Entomologic and virologic factors were investigated to determine whether gray-headed flying foxes (Pteropus poliocephalus) from Indooroopilly Island, Brisbane, Australia could be vertebrate hosts of Ross River (RR) virus. Aedes funereus was the most abundant mosquito species with 6,300-38,700 females per light trap night in the flying fox camp containing gray-headed, black (P. alecto), and little red (P. scapulatus) flying foxes. Sixteen Ae. funereus blood meals from this collection were analyzed by hemoglobin electrophoresis and were found to be from P. alecto. From pledget feeding with RR virus, the infectious dose required to infect 50% of wild caught Ae. funereus was log10 4.2 50% tissue culture infectious doses per mosquito, with a transmission rate to mice of 17% at 9-10 days post infection. Experimental infection of 10 juvenile P. poliocephalus produced viremias of low titer in five animals, with a duration of 1-4 days and a mean of two days. Three percent of colonized Ae. vigilax that fed on the 10 animals during this period became infected. One of the five viremic flying foxes and two of the five aviremic animals produced a detectable immune response by either neutralization or hemagglutination-inhibition tests. Based on the low to moderate vector competence of Ae. funereus for RR virus, and evidence that P. poliocephalus is a poor vertebrate host of RR virus, it is unlikely that RR virus transmission would be maintained between these two species, but it could be maintained by other more competent vector/host pairs.

Aedes↗
PubMed1996

An outbreak of Japanese encephalitis in the Torres Strait, Australia, 1995.

OBJECTIVES: To determine the distribution of virus infection during an outbreak of Japanese encephalitis (JE) in the Torres Strait, and to describe the environmental factors facilitating the outbreak. DESIGN: Human and porcine serological surveys for JE virus activity throughout the Torres Strait, and mosquito and household surveys on the island of Badu. SETTING: The island of Badu (where the clinical cases occurred) and the other islands of the Torres Strait, Australia, during April-May 1995. RESULTS: The serological surveys identified recent JE virus infection among residents or domestic pigs on at least nine outer Torres Strait islands. A JE virus, confirmed by nucleotide sequencing, was isolated from two asymptomatic Badu residents. Virus isolations and mosquito surveys implicated Culex annulirostris as the major vector involved in the outbreak. There was prolific Cx. annulirostris breeding in a variety of water bodies close to and within the Badu community. Over half (53%) of the households kept pigs in pens, and many (63%) of the pigpens were situated near standing water; in 56% of these "wet" pigpens Cx. annulirostris was breeding. CONCLUSIONS: There was evidence of widespread JE virus activity throughout the outer islands of the Torres Strait. We suggest that migratory birds and/or wind-blown mosquitoes could have imported the virus into the Torres Strait from a focus of viral activity, possibly in Papua New Guinea, thereby initiating the outbreak. A combination of environmental factors, with large numbers of domestic pigs in close proximity to human dwellings and mosquito breeding sites, undoubtedly facilitated the outbreak on Badu.

Adult↗
PubMed1996

Molecular characterization of the Japanese encephalitis serocomplex of the flavivirus genus.

The Japanese encephalitis (JE) serocomplex of flaviviruses comprises 10 members, 9 of which: Alfuy (ALF); Koutango (KOU); Kokobera (KOK); Kunjin (KUN); Murray Valley encephalitis (MVE); JE; Stratford (STR); Usutu (USU); and West Nile (WN) have been isolated from Africa, southern Europe, Middle East, Asia, and Australia. The tenth member, St. Louis encephalitis (SLE) virus, is confined to North, Central, and South America. For ALF, KOK, KOU, STR, and USU, no sequence data have as yet been reported, and little molecular phylogeny has been determined for this complex as a whole. Using a rapid, one-step RT-PCR and universal primers, we have amplified and sequenced a 450-600 base pair region of the virus genome encompassing the N terminus of the nonstructural protein NS5 and the 5' end of the 3' noncoding region, for several strains of all of these viruses, except USU and SLE viruses. These data, as well as published sequence data for other flaviviruses, were analyzed with the ClustalW and Phylip computer packages. The resultant phylogenetic data were consistent with some of the current flavivirus serological classification, showing a close relationship between ALF and MVE viruses and between KOK and STR viruses, but suggested that KOK and STR are distantly related to the other viruses and should perhaps be reclassified in their own serocomplex. The data also confirmed the close relationship between KUN and WN viruses and showed that an isolate of KUN virus from Sarawak may represent a "link" between these two virus species. In addition, the primary sequence data revealed a polymorphic region just downstream of the stop codon in the 3' end of the viral genomes.

Amino Acid Sequence↗
PubMed1996

Mosquito-borne viruses and epidemic polyarthritis.

The two most common mosquito-borne viruses associated with epidemic polyarthritis and polyarticular disease are Ross River and Barmah Forest viruses, accounting for about 90% and 10%, respectively, of serologically confirmed cases. Occasional cases of polyarticular disease in Australia have been associated with infection by other mosquito-borne arboviruses, but the role of these viruses in human disease remains to be confirmed.

Alphavirus↗
PubMed1996

Protective immune responses to the E and NS1 proteins of Murray Valley encephalitis virus in hybrids of flavivirus-resistant mice.

The lack of an effective animal model has been a major obstacle in attempts to define the role of humoral and cellular immune responses in protection against flavivirus infection. We have used F1 hybrid mice (BALB/c x C3H/RV) that are heterozygous for the flavivirus resistance allele F1vr and show reduced virus replication in the brain after intracerebral inoculation. F1 hybrid mice challenged by intracerebral inoculation with Murray Valley encephalitis (MVE) virus developed encephalitis 2-3 days later than a genetically susceptible strain (BALB/c) but showed a similar mortality rate. This delay in the onset of disease provided more opportunity for virus clearance by primed immune responses. Using F1 hybrid mice we were able to demonstrate protective immunity induced by structural and non-structural proteins of MVE virus by immunization with pure NS1 protein or recombinant vaccinia viruses that expressed various regions of the MVE genome. These constructs included VV-STR (C-prM-E-NS1-NS2A), VV-delta C (prM-E-Ns1-NS2A) and VV-NS1 (NS1-NS2A). VV-delta C vaccinated mice were completely protected (100% survival)from challenge with 1000 infectious units of MVE virus, while mice inoculated with VV-STR, VV-NS1 or pure NS1 were partially protected (40%, 47% and 85% respectively). Analysis of prechallenge sera and in vivo depletion studies revealed that the solid protection induced by VV-delta C was mediated by neutralizing antibody to the E protein and did not require a CD8+ T cell response. The partial protection provided by VV-STR, VV-NS1 and pure NS1 occurred after induction of antibody to NS1. However, depletion of CD8+ cells prior to virus challenge ablated the protection provided by VV-NS1 indicating some requirement for class I restricted cytotoxic T cells.

Animals↗
PubMed1995

Geographic distribution and evolution of Ross River virus in Australia and the Pacific Islands.

We examined the molecular epidemiology and evolution of Ross River (RR) virus in Australia and the Pacific Islands. Nucleotide sequences of the E2 and E3 genes of five RR virus strains revealed remarkable conservation between 1959 and 1989 with a maximum divergence of only 3.3%. Sequence data from a 505-base pair fragment of the E2 gene from 51 additional strains showed that RR virus has diverged genetically into three separate groups although at least 95% sequence homology was still maintained between all 56 strains. Each genetic type predominates in a particular geographic region of Australia and can be broadly defined as occurring in the western, northeastern, and southeastern regions of Australia. However, some RR virus strains did not follow this pattern of geographic distribution indicating movement of virus by the travel of viremic humans or livestock across the continent. The Pacific Islands isolates all belong to the southeastern genotype. These findings suggest genetic divergence and independent evolution of RR virus within geographically isolated enzootic foci; however, selective pressures maintain high nucleotide conservation in nature.

Australia↗
PubMed1995

An outbreak of Barmah Forest virus disease in the south-west of Western Australia.

OBJECTIVES: To describe the first reported outbreak of Barmah Forest (BF) virus disease in the south-west of Western Australia. DESIGN: Case series correlated with results of arbovirus surveillance. All patients with clinically suspected Ross River (RR) virus infection were serologically tested for antibodies to BF and RR viruses. Home address and date of presentation of patients with serologically confirmed recent infection were recorded. Mosquitoes collected from the districts before and during the BF virus outbreak were identified to species level and tested for virus. RESULTS: Twenty-two cases of BF disease were reported from the region between August 1992 and March 1994. Most occurred in the Peel region in the spring and early summer of 1993. Eighteen isolates of BF virus were obtained from three different species of mosquito trapped between January and October 1993. Fifteen were from mosquitoes in the Peel region and a single isolate was from the Perth metropolitan area. No isolates were obtained from the region before 1993. RR virus was not isolated from mosquitoes trapped in the region during the BF virus outbreak. CONCLUSIONS: Most BF infections were acquired in the Peel region during spring and early summer of 1993. Aedes camptorhynchus mosquitoes were probably the main vectors. The lack of isolations from mosquitoes before 1993 suggests that the virus may have only recently been introduced (or reintroduced) to the region. It was transmitted under conditions that were apparently not conducive to transmission of RR virus.

Adolescent↗
PubMed1995

Glycosylation and antigenic variation among Kunjin virus isolates.

Previous studies have found Kunjin (KUN) virus isolates from within Australia to be genetically homogenous and that the envelope protein of the type strain (MRM61C) was unglycosylated and lacked a potential glycosylation site. We investigated the extent of antigenic variation between KUN virus isolates from Australia and Sarawak using an immunoperoxidase assay and a panel of six monoclonal antibodies. The glycosylation status of the E protein of each virus was also determined by N glycosidase F (PNGase F) digestion and limited sequence analysis. The results showed that KUN viruses isolated within Australia oscillated between three antigenic types defined by two epitopes whose expression was influenced by passage history and host cell type. In contrast an isolate from Sarawak formed a stable antigenic type that was not influenced by passage history and was distinct from all Australian isolates. PNGase F digestions of KUN isolates indicated that 19 of the 33 viruses possessed a glycosylated E protein. Nucleotide sequence of the 5' third of the E gene of selected KUN isolates revealed that a single base change in PNGase F sensitive strains changed the tripeptide N-Y-F (amino acids 154-156 of the published sequence) to the potential glycosylation site N-Y-S. Further analysis revealed that passage history also had a significant influence on glycosylation.

Amidohydrolases↗