Progressive multifocal leukoencephalopathy (PML) typically affects the CNS white matter of the central nervous system. We present an human immunodeficiency virus-infected patient with polyomavirus JC infection restricted to granule cell neurons of the cerebellum and with corresponding neurological symptomatology. Magnetic resonance imaging demonstrated cerebellar atrophy without white matter lesions and stereotactic biopsy showed selective infection of the cerebellar granular cell layer, with preservation of Purkinje cells and absence of classic progressive multifocal leukoencephalopathy histopathology in underlying white matter. Evolution over 8 years was marked by symptomatic improvement corresponding to highly active antiretroviral therapy (HAART), with modest increase in CD4(+) T-cell counts. We propose to call this novel syndrome JCV granule cell neuronopathy (JCV GCN).

Numerous approaches to a quantum theory of gravity posit fundamental ontologies that exclude spacetime, either partially or wholly. This situation raises deep questions about how such theories could relate to the empirical realm, since arguably only entities localized in spacetime can ever be observed. Are such entities even possible in a theory without fundamental spacetime? How might they be derived, formally speaking? Moreover, since by assumption the fundamental entities can't be smaller than the derived (since relative size is a spatiotemporal notion) and so can't 'compose' them in any ordinary sense, would a formal derivation actually show the physical reality of localized entities? We address these questions via a survey of a range of theories of quantum gravity, and generally sketch how they may be answered positively.Comment: 18 pages, 1 figure, accepted for publication in Studies in History and Philosophy of Modern Physic

JCV can productively infect granule cell neurons of the IGCL of the cerebellum. This suggests a role for JCV infection of neurons in cerebellar atrophy occurring in HIV-infected individuals.

Background We sought to determine the prevalence of JCV in bone marrow samples from HIV-positive and HIV-negative patients and whether the bone marrow is a site of latency and neurotropic transformation of JC virus, the agent of progressive multifocal leukoencephalopathy(PML). Methods We collected bone marrow aspirates, archival bone marrow, blood, and urine samples from 75 HIV-negative and 47 HIV-positive patients without PML, as well as bone marrow, and urine or kidney samples from 8 HIV-negative and 15 HIV-positive patients with PML. Samples were tested for JCV DNA by quantitative PCR and JCV protein expression by immunohistochemistry. JCV regulatory regions (RR) were characterized by sequencing. Results JCV DNA was detected in bone marrow specimens of 10/75(13%) of HIV-negative, and 22/47 (47%) of HIV-positive patients without PML, but in 3/8(38%) HIV-negative and 4/15(27%) HIV-positive patients with PML. JCV DNA(2-1081 cps/μg cellular DNA) was detected in multiple leukocyte subpopulations of blood and bone marrow samples. JCV large T antigen, but not VP1 capsid protein, was expressed in bone marrow plasma cells. Bone marrow JCV RR sequences were similar to those usually found in brain of PML patients. Conclusions The bone marrow is an important reservoir and possible site of neurotropic transformation for JCV.