Veterinary and Agricultural Sciences Collected Works - Research Publications

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    CAN VIRAL ENVELOPE GLYCOLIPIDS PRODUCE AUTOIMMUNITY, WITH REFERENCE TO THE CNS AND MULTIPLE-SCLEROSIS
    WEBB, HE ; FAZAKERLEY, JK (BLACKWELL SCIENCE LTD, 1984-01-01)
    Many viruses, with lipid envelopes derived from the host cell membranes, have been implicated in the aetiology of multiple sclerosis (MS), and epidemiological studies support an infectious agent. Alternatively the disease is thought by other workers to be auto-immune in nature, and recently much attention has been focused on immunological sensitivity to glycolipids in MS patients. In this paper it is proposed that CNS demyelination could arise in susceptible individuals (HLA type) from an immune response to glycolipids, triggered by the carrier effect of one or more enveloped neurotropic viruses.
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    DO HUMAN T-LYMPHOTROPHIC VIRUSES (HTLVS) AND OTHER ENVELOPED VIRUSES INDUCE AUTOIMMUNITY IN MULTIPLE-SCLEROSIS
    DALGLEISH, AG ; FAZAKERLEY, JK ; WEBB, HE (WILEY, 1987-07-01)
    A virally induced autoimmune reaction may be important in the pathogenesis of multiple sclerosis. The role that glycolipids and myelin basic protein presented to the virus may play in this process is considered. The most likely cells to be the source of autoantigens are neurons, myelin and oligodendrocytes. Viral infection of class II-expressing cells and association of the viral envelope autoantigens and the class II molecules could trigger an autoimmune reaction. It is suggested that for MS to develop following a virus infection the virus will need to cause expression of class II antigens on brain cells as well as fulfill the same role as an antigen presenting cell. The part which T-lymphotrophic viruses (HTLVs) and other enveloped viruses may play in this phenomenon is discussed.
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    PATHOGENESIS OF VIRUS-INDUCED DEMYELINATION
    FAZAKERLEY, JK ; BUCHMEIER, MJ ; Maramorosch, K ; Murphy, FA ; Shatkin, AJ (ELSEVIER ACADEMIC PRESS INC, 1993-01-01)
    Demyelination is a component of several viral diseases of humans. The best known of these are subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML). There are a number of naturally occurring virus infections of animals that involve demyelination and many of these serve as instructive models for human demyelinating diseases. In addition to the naturally occurring diseases, many viruses have been shown to be capable of producing demyelination in experimental situations. In discussing virus-associated demyelinating disease, the chapter reviews the architecture and functional organization of the CNS and considers what is known of the interaction of viruses with CNS cells. It also discusses the immunology of the CNS that differs in several important aspects from that of the rest of the body. Experimental models of viral-induced demyelination have also been considered. Viruses capable of producing demyelinating disease have no common taxonomic features; they include both DNA and RNA viruses, enveloped and nonenveloped viruses. The chapter attempts to summarize the important factors influencing viral demyelination, their common features, and possible mechanisms.
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    Computer analysis suggests a role for signal sequences in processing polyproteins of enveloped RNA viruses and as a mechanism of viral fusion.
    Fazakerley, JK ; Ross, AM (Springer Science and Business Media LLC, 1989-05)
    We have used a computer program to scan the entire sequence of viral polyproteins for eucaryotic signal sequences. The method is based on that of von Heijne (1). The program calculates a score for each residue in a polyprotein. The score indicates the resemblance of each residue to that at the cleavage site of a typical N-terminal eucaryotic signal sequence. The program correctly predicts the known N-terminal signal sequence cleavage sites of several cellular and viral proteins. The analysis demonstrates that the polyproteins of enveloped RNA viruses--including the alphaviruses, flaviviruses, and bunyaviruses--contain several internal signal-sequence-like regions. The predicted cleavage site in these internal sequences are often known cleavage sites for processing of the polyprotein and are amongst the highest scoring residues with this algorithm. These results indicate a role for the cellular enzyme signal peptidase in the processing of several viral polyproteins. Not all high-scoring residues are sites of cleavage, suggesting a difference between N-terminal and internal signal sequences. This may reflect the secondary structure of the latter. Signal sequences were also found at the N-termini of the fusion proteins of the paramyxoviruses and the retroviruses. This suggests a mechanism of viral fusion analogous to that by which proteins are translocated through the membranes of the endoplasmic reticulum at synthesis.
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    THE V5A13.1 ENVELOPE GLYCOPROTEIN DELETION MUTANT OF MOUSE HEPATITIS-VIRUS TYPE-4 IS NEUROATTENUATED BY ITS REDUCED RATE OF SPREAD IN THE CENTRAL-NERVOUS-SYSTEM
    FAZAKERLEY, JK ; PARKER, SE ; BLOOM, F ; BUCHMEIER, MJ (ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS, 1992-03-01)
    Following intracerebral inoculation of adult Balb/c Byj mice, the MHV-4 strain of mouse hepatitis virus (MHV) had an LD50 of less than 0.1 PFU, whereas its monoclonal antibody resistant variant V5A13.1 had an LD50 of 10(4.2) PFU. To determine the basis for this difference in neurovirulence we have studied the acute central nervous system (CNS) infection of these two viruses by in situ hybridization. Both viruses infected the same, specific neuroanatomical areas, predominantly neurons, and spread via the cerebrospinal fluid, along neuronal pathways and between adjacent cells. The neuronal nuclei infected and the spread of virus within the brain are described. The main difference between the parental and variant viruses was the rate at which the infection spread. MHV-4 spread rapidly, destroying large numbers of neurons and the animals died within 4 days of infection. The variant virus spread to the same areas of the brain but at a slower rate. This difference in the rate of virus spread was also apparent from the brain virus titers. The slower rate of spread of the variant virus appears to allow intervention by the immune response. Consistent with this, the variant virus spread slowly in athymic nu/nu mice, but in the absence of an intact immune response, infection and destruction of neurons eventually reached the same extent as that of the parental virus and the mice died within 6 days of infection. We conclude that the V5A13.1 variant of MHV-4 is neuroattenuated by its slower rate of spread in the CNS.
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    THE EMERGING ROLE FOR AGRICULTURAL EDUCATION IN PRODUCING FUTURE RESEARCHERS
    Falvey, L ; Maguire, C (Journal of International Agricultural and Extension Education, 1997-01-01)
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    INSTITUTIONAL ARRANGEMENTS IN AGRICULTURAL EDUCATION, EXTENSION, AND RESEARCH: LESSONS FOR INTERNATIONAL DEVELOPMENT
    Falvey, L ; Forno, D (Journal of International Agricultural and Extension Education, 1997-01-01)
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    Formal Agricultural Education: Origins of Agricultural Knowledge Systems
    Falvey, J (Asian Agri-History Foundation, 1997)
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    Attracting the Shining Stars to Agriculture.
    Falvey, J (Australian Institute of Agricultural Science and Technology, 1997)
    While one will expect partnerships of convenience from time to time. the long-term prospect for agricultural education is based on the recognition of its role as an applied area of social and natural sciences supporting agriculture. Industry and research funders. among others. are also sending this message (Falvey and Ma!!hews. 1997). As an applied field, it behoves us to link strongly with all stakeholders in policy formulation. planning. implementation and funding.
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    Food and Environmental Science
    Falvey, J (Australian Science Teachers Association, 1997)
    The negative impact of food production on the environment is of increasing public concern and more sensitive production systems such as organic farming are often proposed. Such views miss the point that this global issue must be considered in terms of essential tradeoffs which require more and better science in the fields of food and environment, such as in agricultural science courses. Global population will continue to grow and demographic shifts and poverty will require massive increases in food production which can only be provided from intensive agriculture. Declining food prices and extreme poverty in some countries will continue to orient food producers to short term gains. All of these factors suggest that intensive agriculture restricted to suitable lands will be required for the foreseeable future. Balancing environmental care with food production is a challenge which continues to demand the best minds for research and education. We cannot isolate ourselves from the world in which we live.