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We have examined the effects of the antimicrotubule agent benomyl and several mutations on nuclear and mitochondrial movement in germlings of the filamentous fungus Aspergillus nidulans. While, as previously reported, benomyl inhibited nuclear division and movement, it did not inhibit mitochondrial movement. To test the effects of benomyl more rigorously, we germinated two benomyl super-sensitive, ~-tubulin mutants at a benomyl concentration 50-100 times greater than that required to inhibit colony formation completely. Again nuclear division and movement were inhibited, but mitochondrial movement was not. We also examined conditionally lethal ~-tubulin mutations that disrupt microtubule function under restrictive conditions. Nuclear division and movement were inhibited but, again, mitochondrial movement was not. Finally we examined the effects of five heat-sensitive mutations that inhibit nuclear movement but not nuclear division at restrictive temperatures. These mutations strongly inhibited nuclear movement at a restrictive temperature but did not inhibit mitochondrial movement. These data demonstrate that the mechanisms of nuclear and mitochondrial movement in Aspergillus nidulans are not identical and suggest that mitochondrial movement does not require functional microtubules.OrganeUar translocation in its many forms is essential to the growth and maintenance of most, if not all, eukaryotic ceils. In recent years organellar translocation has been studied extensively in many organisms (reviewed in reference 18) and while there is now good evidence that some forms of organellar translocation are microtubule-mediated (2,19,22,23; and other data reviewed in reference 18) and others are mediated by actin microfilaments (reviewed in reference 18), the mechanisms of force production and the mechanisms by which force production is regulated are not known. We are studying organellar translocation in the filamentous fungus Aspergillus nidulans because this organism has a very good genetic system that makes it possible to apply the power of genetics to analyze the mechanisms of organellar translocation. Mutations in genes that encode the microtubule proteins a and/~ tubulin have been isolated in this organism (12,15,20) as have mutations that specifically inhibit nuclear movement (11,14). These mutations have been used to demonstrate that nuclear movement is microtubule-mediated (14, 15). Our long-term goal is to identify the components of the organellar translocation apparatus(es) in A. nidulans and to determine how these components interact to produce organeUar movement.One of our initial goals has been to determine if there is 2392 but a single mechanism responsible for the translocation of organelles in A. nidulans or if there are two or more mechanisms as there apparently are in some organisms (reviewed in reference 18). We have, consequently, examined the movement of mitochondria from conidia (asexual spores) into germ tubes in the presence of the antimicrotubule agent benomyl and in strains that carry...

Studies demonstrated that a strain derived from an infectious clone of coxsackievirus B1 (CVB1N) (N. Iizuka, H. Yonekawa, and A. Nomoto, J. Virol. 65:4867-4873, 1991) was 3 to 4 log 10 less virulent than the myotropic Tucson strain of CVB1 (CVB1T) following intraperitoneal inoculation of newborn mice. Replacement of nucleotides (nt) 69 to 804 from the 5 untranslated region (5 UTR) and 1A coding region of CVB1N or nt 117 to 161 from the 5 UTR with the corresponding part from CVB1T restored greater than 90% of the virulence. Sequencing of the 5 UTR of CVB1T demonstrated areas with a greater similarity to particular echoviruses than to CVB1N, suggesting that recombination events might have occurred, perhaps influencing the virulence phenotype.

The DA strain of Theiler's murine encephalomyelitis virus, a member of the cardiovirus genus of picornaviruses, induces a restricted and persistent infection associated with a demyelinating process following intracerebral inoculation of mice; both virus infection and the immune response are believed to contribute to the late white matter disease. We now report that intraperitoneal inoculation with DA produces an acute myositis that progresses to a chronic inflammatory muscle disease in CD-1 mice as well as several inbred mouse strains. Some mouse strains also develop central nervous system white matter disease and a focal myocarditis. Infectious virus in skeletal muscle falls to undetectable levels 3 weeks postinoculation (p.i.), although viral genome persists for at least 12 weeks p.i., the longest period of observation. Severe combined immunodeficient animals have evidence of muscle pathology as long as 5 weeks p.i., suggesting that DA virus is capable of inducing chronic muscle disease in the absence of an immune response. The presence in immunocompetent mice, however, of prominent muscle inflammation in the absence of infectious virus suggests that the immune system also contributes to the pathology. T lymphocytes are the predominant cell type infiltrating the skeletal muscle during the chronic disease. This murine model may further our understanding of virus-induced chronic myositis and help to clarify the pathogenesis of human inflammatory myopathies.

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