David A. Fuccillo

Isolation of measles virus from brain cell cultures of two patients with subacute sclerosing panencephalitis.

Summary Measles virus was isolated from brain cell tissue cultures derived from two SSPE patients. These cultures proved to contain intracellular measles antigen which was not released in the fluid phase. Infectious, complete virus was obtained when mixed cultures containing the brain cells and HeLa cells were prepared. It appears that SSPE is due to suppressed measles virus infection. Once “rescued” through the mixed culture technique, the virus recovered from SSPE patients proved indistinguishable from measles virus. Note added in proof: At the time of galley review of this paper, confirmation of our previous isolation of complete infectious measles virus was reported by Payne, F. E., Baublis, J. V. and Itabashi, H. H. (Isolation of Measles Virus from Cell Cultures of Brain from a Patient with Subacute Sclerosing Panencephalitis, New England Journal of Medicine 281, 585, 1969). These authors used the mixed culture technique which we reported for this purpose (Horta-Barbosa, L., Fuccillo, D. A., Sever, J. L. and Zeman, W., Subacute Sclerosing Panencephalitis: Isolation of Measles Virus from a Brain Biopsy, Nature 221, 974, March 8, 1969) with BSC-1 cells and continued propagation of the patients brain cells. The authors gratefully acknowledge the valuable technical assistance of Miss Rebecca Schronce and Mrs. Anna Barbara Wittig.

Subacute sclerosing panencephalitis: isolation of suppressed measles virus from lymph node biopsies.

Measles virus was isolated in mixed cultures of lymph node cells and HeLa cells. The agent was isolated by cocultivation from biopsy specimens of two of five patients with subacute sclerosing panencephalitis. The virus was identified by hemagglutination-inhibition, immunofluorescent, and neutralization tests. Biopsies from controls did not show evidence of measles virus.

Herpesvirus hominis Types I and II: A Specific Microindirect Hemagglutination Test

Summary A microindirect hemagglutination test (IHA) for the determination of type-specific antibody to Herpesvirus homin-is (Types I and II) was developed and evaluated in comparison to the quantitative microneutralization procedure. Paired human sera from 14 patients with complement-fixing antibody rises to herpesvirus were tested with all three methods. The IHA test, as described, appears to be rapid, simple and valuable technique for a detection of Type I and Type II herpesvirus infections and may be useful for classifying herpesvirus isolates. We wish to acknowledge the technical assistance of Mrs. Anita Ley, Mr. Melvin Hess, and Miss Sally Hensen.

Genital Herpesvirus Hominis Type 2 Infection: An Experimental Model in Cebus Monkeys

Genital infection with herpesvirus hominis type 2 was established in ten female cebus monkeys. Clinical and laboratory findings in the cebus mimic closely those observed in humans, thus providing an experimental model which may be used in the study of the possible role of genital herpetic infection in cervical cancer and in perinatal and chronic neurological diseases.

Subacute sclerosing panencephalitis: Destruction of human brain cells by antibody and complement in an autologous system

Abstract Cultured cells from the brain of a patient with subacute sclerosing panencephalitis (SSPE), a disease associated with chronic measles virus infection, were lysed by that patients own serum. Lysis was dependent on the presence of antibody(s) to measles virus and complement. Lysis, which occurred only when measles viral antigens were expressed on the cell surface, could be induced by sera and cerebral spinal fluid (CSF) from other patients with SSPE, sera from patients who had convalesced from normal measles virus infection, and heterologous rabbit serum against measles virus. Further, complement-binding immune complexes were found in the sera and CSF of patients with SSPE. These studies clearly document that patients with SSPE contain a functioning humoral attack system against cells expressing surface measles virus antigens.

Specific inhibitory factors of cellular immunity in children with subacute sclerosing panencephalitis.

Employing a 51Cr release cytotoxicity microassay, and using both measles-and SSPE-infected target cells, four patients with documented SSPE were evaluated for specific cellular and humoral immunity. Mononuclear leukocytes from SSPE patients and control subjects exhibited comparable cytotoxicity. Serum and CSF from these SSPE patients inhibited the cellular response to SSPE-infected cells but not to measles-infected cells. Moreover, fresh whole serum alone from control donors produced significant 51Cr release from both cell lines, whereas SSPE whole serum was effective only against measles-infected cells. CSF from an additional ten patients with SSPE was examined for inhibitory activity: seven of these completely blocked and one partially blocked cell-mediated cytotoxicity to SSPE-infected cells. Preliminary characterization of the serum inhibitory factor suggested that it is IgM or antigen-antibody complexes. These data also suggest antigenic differences between the SSPE and measles viruses.

Antibody to human and simian retrovirus, HTLV-I, HTLV-II, HIV, STLV-III, and SRV-I not increased in patients with multiple sclerosis.

We have tested sera from patients with multiple sclerosis, matched controls, and those with other neurological diseases, as well as sera from patients with the acquired immunodeficiency syndrome and controls and patients with tropical spastic paraparesis (TSP) and controls for antibody to human T‐lymphotropic virus type I (HTLV‐I), HTLV‐II, human immunodeficiency virus (HIV), simian T‐lymphotropic virus type III, or simian retrovirus type I by immunofluorescent activity test, and for HTLV‐I and HIV by the ELISA method. Sera from patients with multiple sclerosis and matched controls, and from patients with optic neuritis and Parkinsons or other neuromuscular diseases did not have antibody to any of the retroviruses tested. Specimens from TSP patients and some controls contained HTLV‐I antibody. We conclude from our study that only TSP patients had serological evidence of infection with one of the retroviruses studied.

Serologic studies of MS patients, controls, and patients with other neurologic diseases Antibodies to HTLV‐I, II, III

We have studied the frequency of human retrovirus antibody (HTLV-I, II, III) in the serum and CSF of patients with MS, matched controls, and patients with optic neuritis, idiopathic and postencephalitic Parkinsons disease, neuropathies, polymyositis, ALS, and postpoliomyelitis. Except for the postpoliomyelitis samples, all samples were collected prior to 1980. Contrary to a previous published report, no significant levels of antibody to HTLV-I, II, or III were found in the MS patients or controls. No retrovirus antibody was detected in patients with the other neurologic diseases.

Persistent Rubella Virus Production in Embryonic Rabbit Chondrocyte Cell Cultures

Summary Cell cultures were established from embryonic rabbit sternum. Persistent virus infected lines were established by inoculation of rubella virus at passages 26 and 42 and have produced rubella virus at titers of 104 or higher for 78 subcultures. The presence of virus in these cultures changed the epithelial-like morphology seen in the control cells to fibroblastic-like.

Multiple sclerosis: attempts to demonstrate altered immune responses and viruses.

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