Movement Disorders Vol. 7, No. 2, 1992, pp. 153-158 0 1992 Movement Disorder Society Cerebrospinal Fluid Antibodies to Coronavirus in Patients with Parkinsons Disease Enrico Fazzini, *John Fleming, and Stanley Fahn Department of Neurology, College of Physicians and Surgeons, Columbia-Presbyterian Medical Center, New York, New York; *Department of Neurology, University o f California at Los Angeles, Los Angeles, California, U.S.A. Summary: The etiology of Parkinsons disease remains unknown, and a search for environmental agents continues. In 1985, Fishman (10) induced infection of the basal ganglia by a coronavirus in mice. Although coronavirus is recognized primarily as a respiratory pathogen in humans, its affinity for the basal ganglia led us to investigate its possible role in human Parkinsons disease. The cere- brospinal fluid of normal controls (CTL) (n = 18), and patients with Parkin- sons disease (PD (n = 20) and other neurological disease (OND) (n = 29) was analyzed in a blinded manner by enzyme-linked immunosorbent assay mea- surements in optical density (OD) units for antibody response to four coro- navirus antigens: mouse hepatitis virus JHM (J) and A59 (A), and human coronavirus 229E (E) and OC43 (0). When compared with CTL, PD patients had an elevated (p 0.05) to 0 (0.0839 vs. 0.0071) was greater than that to E (0.1261 vs. 0.0743). When compared to OND, PD patients had an elevated mean OD response to J (0.0856 vs. 0.0267, p 0.05) to A (0.1722 vs. 0.0929) and 0 (0.0839 vs. 0.0446) were greater than that to E (0.1261 vs. 0.0946). These results suggest that there may be an association between coronavirus and PD. Key Words: Parkinsons diseas+Coronavirus- Environmental factors. The etiology of Parkinsons disease (PD) remains unknown, although it is probable that there exists a multitude of environmental agents that have in com- mon a selective affinity for the substantia nigra (1- 3). Viruses that have been implicated in causing en- cephalitis and parkinsonism include those responsi- ble for the epidemic in the early 1900s (1916-1930) known as von Economos encephalitis, western equine, coxsackie, and Japanese B viruses (4). Coronaviruses are a group of RNA-containing vi- ruses named for their widely spaced, club-shaped surface projections. Coronaviruses were first iso- Address correspondence and reprint requests to Dr. E. Fazzini at New York University Medical Center, 650 First Av- enue, 4th floor, New York, NY 10016, U.S.A. lated from humans in the mid-1960s in patients with the common cold (5). There are at least 10 species that have been identified, including human corona- virus (HCV), murine hepatitis virus (MHV), bovine coronavirus (BCV), haemagglutinating encephalo- myelitis virus (HEV) of pigs, infectious bronchitis virus (IBV) of chicken, turkey coronavirus (TCV), and others (6,7). There are three distinct antigenic groups into which the 10 species are classified; HCV of the OC43 strain bear antigenic resemblance to the first group (along with MHV, BCV, and HEV), whereas those HCV of the 229E strain share common antigens with the second group (8). Coro- naviruses are capable of producing both acute and chronic persistent infections in humans and ani- mals; natural transmission between species is pos- 153 154 E. FAZZINI ET AL. sible leading to clinically inapparent or atypical in- fections (9). In 1985, Fishman et al. (10) reported a selective affinity of coronavirus MHV-A59 for the basal gan- glia in C57 Black mice. Mice were observed to have a hunched posture with marked locomotion diffi- culty. Death due to encephalitis or hepatitis usually occurred within 2 weeks. Animals demonstrated ex- tra- and intracellular vacuolation, neuronal loss, and gliosis in the substantia nigra and subthalamic nucleus. It had been previously thought that only the JHM strain of MHV was capable of infecting neurons, producing demyelination and encephalitis (1 1). In 1955, Kersting and Pette demonstrated that MHV- JHM was capable of causing localized infection of the basal ganglia in monkeys (12). The findings of Fishman et al. (10) raised the possibility that other species of coronaviruses might also have the pro- pensity to induce parkinsonism. The present inves- tigation was undertaken in order to determine if pa- tients with Parkinsons disease had any evidence of central nervous system infection with coronavi- ruses. MATERIALS AND METHODS Viruses and Cells For this study, HCV-229E was grown on mono- layers of L132 cells (13). The HCV-OC43 was prop- ogated on HRT cells (14). The identity of these vi- ruses was confirmed in binding assays with the use of reference antisera (nos. V-361-501-588 and V-360-701-562; National Institutes of Health, Be- thesda, MD, U.S.A.). The MHV-JHM and MHV- A59 were grown on DBT cells as previously described (15). Each virus was prepared under se- rum-free conditions. Supernatants from infected cultures were clarified by centrifugation at 400 g for 10 min and stored