MOLECULAR BIOLOGY OF HUMAN VIRUS INFECTIONS, HIV-1 AND JCV

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Progressive multifocal leucoencephalopathy (PML) and AIDS encephalopathy are viral induced neurological diseases which occur almost exclusively in individuals whose immune systems are impaired. We have investigated the molecular pathogenesis of these diseases by developing laboratory assays that examine the human polyomavirus, JCV, and the human immunodeficiency virus, HIV-1, the causes of PML and AIDS encephalopathy, respectively. We have developed a new methodology that prepares brain biopsy tissue for in situ DNA hybridization to detect viral genomes on the same day of surgery. For example, in brain biopsy tissue from an AIDS patient with PML, JCV DNA can be detected using a non-radioactive, nucleic acid probe. Data from this rapid molecular diagnostic assay facilities patient management decisions on a more timely basis. We have also examined protein interactions between JCV and infected glial cells. The non-structural JCV T protein can bind the cellular retinoblastoma protein which normally functions for growth regulation. Results from this study suggest that the oncogenic properties of JCV may be related to viral proteins interfering with normal cellular metabolism. Other human viruses have been studied for their association with glial cells of the nervous system. Astroglial cells from human fetal brain respond very rapidly to the introduction of the HIV-1 genome. AIDS virus proteins are synthesized within hours of transfection. However, HIV-1 infection of astrocytes results in a persistent infection without cytopathic effects. Varicella-zoster virus, the agent which causes shingles, can productively infect Schwann cells, the myelinating cell of the peripheral nervous system. VZV proteins are also produced very rapidly following infection and are efficiently assembled into progeny virions.