Many patients have diseases that may be caused by virus infections, but for which a cause cannot be found by conventional laboratory testing. We collaborated with Philip Krause at the FDA to look for new viruses in patients with unexplained diseases. We followed a patient who underwent hematopoietic stem cell transplantation of systemic lupus erythematosis who developed an unexplained pneumonia. Despite an extensive evaluation, including an open lung biopsy, a definitive diagnosis of her pneumonia was not possible and she died of respiratory failure. Using a novel PCR based assay that involves random primers, we identified human coronavirus HKU1 RNA in bronchoalveolar lavage fluid at autopsy. The virus was subsequently detected in lung tissue from autopsy and electron microscopy identified viral particles compatible with a coronavirus both from autopsy and from the lung biopsy sample. This is the first report documenting this virus in the lung of a patient with a fatal pneumonia. We have also initiated a clinical study using CMX-001, a lipid-conjugated form of cidofovir, which has excellent oral bioavailability and lacks the kidney toxicity of cidofovir, in patients with severe herpes simplex, adenovirus, and cytomegalovirus infections. In addition to these studies, we collaborated with Eugene Major in the National Institute of Neurologic Disorders and Stroke at NIH to study the effect of CMX-001 on replication of JC virus in vitro. JC virus is a polyomavirus that causes progressive multifocal leukoencephalopathy, which is usually a fatal neurologic disease in immunocompromised persons. CMX-001 resulted in a dose dependent reduction in the number of JC virus-infected cells in tissue culture and nearly eliminated JC virus from an established cell culture. CMX-001 reduced the number of copies of JC virus in infected cells. The drug had minimal cell toxicity when used at concentrations that reduced JC virus infection in vitro. This study suggested that CMX-001 has potential in the treatment of JC virus infections in immunocompromised patients.
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