W. T. London

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.

MODIFICATION OF CHRONIC HEPATITIS-B VIRUS INFECTION IN CHIMPANZEES BY ADMINISTRATION OF AN INTERFERON INDUCER

Chimpanzees chronically infected with hepatitis-B virus showed transient changes in several markers of infection when treated with the interferon inducer polyriboinosinic-polyribocytidylic acid-poly-l-lysine carboxymethyl cellulose. Serum Dane-particle-associated D.N.A. polymerase, e antigen and hepatitis-B surface antigen, and intrahepatic hepatitis-B surface and core antigens diminished during treatment. Defective (D.N.A.-polymerase-negative) Dane particles increased in titre transiently during treatment; these may play a role in the modulation of hepatitis-B virus infection. Humoral immune responses in chronic hepatitis-B carrier chimps were unaffected. Interferon inducers (or exogenous interferon) may be useful for the treatment of chronic hepatitis-B virus infection.

Differences among Isolates of Simian Hemorrhagic Fever (SHF) Virus

Abstract Simian hemorrhagic fever (SHF) virus is a member of the Togaviridae family which currently is unclassified to genus. We have studied the relatedness of four different SHF virus isolates obtained from infected macaque or patas monkeys. Differences were found among isolates in type and severity of disease produced in patas monkeys, cell sensitivity to infection, viral antigens, and levels of specific antibody induced in patas monkeys. Based on these criteria, the four isolates have been grouped in two categories: those producing acute infections in patas monkeys (LVR, P-180) and those producing persistent infections (P-248, P-741). The P-180 isolate induced the most severe disease in experimentally infected patas monkeys, but only occasionally were their infections fatal. Persistently infected patas monkeys were viremic over a period of years, but showed no signs or symptoms of infection. All four isolates were found to be antigenically related by use of enzyme-linked immunosorbent assay (ELISA); the P-248 isolate showing the weakest antigenic relationship. However, none of the four isolates induced cross-neutralizing antibodies in infected patas monkeys. High titers of specific IgG antibody (up to 31,250 as determined by ELISA) were induced in acutely infected patas monkeys (LVR, P-180), but antibody was barely detectable (≤50) in persistently infected patas monkeys (P-248, P-741). LVR lyrically infected USU-104 cells, patas monkey peritoneal macrophages (PMAC), and rhesus monkey PMAC. The P-180 isolate lytically infected both patas monkey PMAC and rhesus monkey PMAC, but not USU-104 cells. The isolates producing persistent infections (P-248, P-741) lytically infected only-rhesus monkey PMAC. These results show that marked differences exist among isolates of SHF virus from naturally infected animals. These differences should be useful in categorizing new isolates.

Morphological Changes of an Inflammatory Myopathy in Rhesus Monkeys with Simian Acquired Immunodeficiency Syndrome

Abstract Eleven of 25 rhesus monkeys which died of simian acquired immunodeficiency syndrome (SAIDS) caused by infection with a type D retrovirus related to Mason-Pfizer monkey virus showed evidence of muscle weakness and atrophy and had elevated levels of muscle enzymes. Biopsies of affected muscle studied with enzyme histochemistry showed the characteristic features of polymyositis. Inflammatory cells consisting of lymphocytes, macrophages, and large vacuolated bizarre-shaped cells of undetermined type were surrounding or invading muscle fibers and were present in the perivascular spaces and endomysia septa. Within the perivascular infiltrates, lymphocytes were abundant but very few macrophages were present. Other myopathic features including profound proliferation of fibrous tissue, necrosis, and phagocytosis of muscle fibers were noted to a variable degree. The retrovirus was isolated from affected muscles. The clinical and historical features of polymyositis in rhesus monkeys with SAIDS are very similar to those of human polymyositis. The polymyositis in SAIDS induced by a type D retrovirus related to Mason-Pfizer monkey virus is an excellent primate model to study the mechanism and morphological changes of viral-induced muscle damage.

Elimination of Persistent Simian Hemorrhagic Fever (SHF) Virus Infection in Patas Monkeys

Abstract Devastating epizootics of simian hemorrhagic fever (SHF) have been iatrogenically initiated in captive colonies of macaque monkeys by strains of SHF virus emanating from asymptomatic persistently infected patas monkeys. We have found that persistently infected patas monkeys can be cleared of their infection by superinfection with strains of SHF virus which cause acute infections in this species. All 20 persistently infected animals subjected to this procedure have been cleared of their infection within 3 months. These animals were shown to be virus free by the most sensitive in vitro and in vivo tests currently available and periodic tests of serum from these animals over several years have shown them to remain virus free. Superinfection has in some cases caused some adverse clinical symptoms (anorexia, lethargy, facial edema, dehydration, and mild subcutaneous hemorrhages), but with supportive care, no fatal infections have occurred. Thus, superinfection with acute strains of SHF virus is a highly effective method of eliminating persistent infection in patas monkeys.

Transmission of Simian Acquired Immunodeficiency Syndrome (Saids) with Type D Retrovirus Isolated from Saliva or Urine

Abstract Saliva and urine specimens from rhesus monkeys with SAIDS were found to contain a type D retrovirus related to Mason-Pfizer monkey virus (MPMV) which has been linked etiologically to SAIDS. Virus i so1ates from sal i va and uri ne were shown to have the characteristics of the SAIDS agent by their reverse transcriptase divalent cation preference for synthetic template-primers, production of characteristic cytopathology in Raji cells and antigenic relat.edness to MPMV as determined by enzyme-linked immunosorbent assay (ELISA) and competition radioimmunoassay (RIA). Electron micrographs of parot id tissue from an anima1 with SAIDS also showed budding particles with type D retrovirus morphology. A tissue culture grown virus isolate from urine of an animal with SAIDS, produced SAIDS when inoculated into two normal juvenile rhesus monkeys. Since saliva and urine of monkeys with SAIDS contain infectious SAIDS virus, they are 1ikely sources of virus by which the disease is naturally transmitted. Thus, care should be taken to avoid contact of normal and infected animals.

Antibody Response of Various Strains of Rubella Virus When Inoculated into Rabbits

Summary The inoculation of New Zealand white rabbits with four low passage or wild rubella virus strains and four vaccine strains gave differences in antibody response and virus shedding. These differences can be useful as markers of strain differences and for studies of mechanisms of attenuation. The low passage wild virus strains produced high antibody levels and variable amounts of virus shedding. The vaccine strains resulted in little or no antibody and no virus shedding.