John L. Sever

Involvement of JC Virus–Infected Mononuclear Cells from the Bone Marrow and Spleen in the Pathogenesis of Progressive Multifocal Leukoencephalopathy

PROGRESSIVE multifocal leukoencephalopathy (PML), a subacute demyelinating disease resulting from infection of oligodendrocytes by JC virus, occurs almost exclusively in immunocompromised patients....

Cellular immune factors associated with mother-to-infant transmission of HIV

ObjectiveTo study a possible correlate of protection in mother-to-infant transmission of HIV infection. In particular, to determine whether lack of HIV-specific T-helper (TH) function as indicated by HIV and non-HIV antigen-stimulated interleukin (IL)-2 production of mother and/or newborn peripheral blood leukocytes (PBL) is associated with mother-to-infant transmission of HIV. MethodsPBL from 21 HIV-seropositive pregnant women and 23 cord blood leukocytes (CBL) from their offspring were studied for in vitro TH function by IL-2 production in response to HIV and non-HIV antigens. Polymerase chain reaction (PCR) and viral culture assays were performed to determine HIV infection of the infants. ResultsPBL from 10 out of 21 (48%) mothers and from eight out of 23 (35%) CBL samples responded to two or more out of five synthetic gp160 envelope (env) peptides. Three of the 23 (13%) offspring were shown to be HIV-infected by PCR and/or viral culture on follow-up. All three infected infants were from a subset whose CBL did not exhibit env-specific TH immunity. ConclusionOur results demonstrate that fetal T cells can be primed to HIV env determinants in utero, suggest that HIV-specific TH immunity may be protective in newborns, and provide a possible means for identifying newborns who are at risk for HIV infection.

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.

Cytomegalovirus infections in newborn infants

A study of the frequency of congenital cytomegalovirus (CMV) infections and the associated clinical findings included 545 children. Urine specimens were obtained within the first 24 hours of life. Cultures of these specimens revealed that 3 infants were excreting CMV. None of the 3 had classical cytomegalic inclusion disease; however, each had transient abnormalities in the first year of life. In 2 cases, IgM levels were elevated. No neutralizing antibody was found in 2 of the cord sera. All patients later showed neutralizing antibody. This reaction was highly specific with a low passage isolate from one of the patients. CF antibody response was variable. Virus excretion persisted in the children throughout observation. There were familial infections but no evidence of disease.

Cytomegalovirus in the normal pregnant woman

Abstract A study was undertaken to determine the prevalence of cytomegalovirus in the mother and newborn infant in a normal pregnant population and to determine its possible relationship to outcome. Two hundred and ten maternal urine samples were tested. Cytomegalovirus was recovered from several pregnant women and was demonstrated in the urine of one infant born to a mother with viruria. This infant had hypospadias, the only significant neonatal morbidity, and mortality could not be correlated with viruria at the time of delivery.

Measles antibody titers of multiple sclerosis patients and their siblings

Results of numerous investigations indicate that measles antibody titer is slightly but consistently higher in multiple sclerosis (MS) patients than in controls (references listed in the appendix). Previously we reported titers to measles and several other viral antigens to be higher in MS patients than in controls but not higher than in their siblings of the same sex.’ j2 Since MS is not recognized as a familial disease, this result was ~ n e x p e c t e d . ~ We designed the present study to determine measles antibody titer in an independent group of patients and siblings.

Congenital rubella syndrome with immunoglobulin disorder

A child with the congenital rubella syndrome and immunoglobulin abnormalitiescharacterized by a tremendous increase in IgM, delayed appearance of IgG, and absence of IgA, is described. “Rheumatoid factor” and cold agglutinins were present. Treatment with an antiviral agent, l-adamantanamine, was thought to result in clinical improvement. An unusual feature of the case was the late development of retinitis and cataracts.

Isolation of rubella virus from products of conception

Abstract The products of conception from 50 therapeutic abortions for maternal rubella in either the first or second trimester were studied using virus isolation procedures. Rubella virus was isolated from 32 (64 per cent) of the specimens. Within the limits of the study it could be demonstrated that the rubella virus was capable of infecting the products of conception, and that once infection was established the virus persisted within the products of conception as late as the seventy-seventh day following the onset of rash. For 8 infected fetuses it was possible to study individual organs. The placenta was involved in all 8 cases. In addition, isolations were achieved from brain, eye, inner ear, heart, thymus, lung, kidney, adrenal glands, gonads, spleen and the gastrointestinal tract in 2 cases, and from the heart in 1 case. This study suggests that the establishment of infection by the rubella virus within the placenta may be a very frequent phenomenon with maternal rubella in the first 4 months of gestation. The possible critical role of the placenta in determining whether infection of other fetal tissues occurs is discussed.

Serum immunoglobulin levels in newborn infants. II. Survey of cord and follow-up sera from 123 infants with congenital rubella

The value of determining serum immunoglobulin levels as a screening test for intrauterine infection was evaluated in 123 infants with documented congenital rubella and in control subjects. Data collected from cord blood and from specimens obtained during the first 36 months of life were submitted to statistical analysis. Elevation of cord IgM values (20 mg. per cent or above) was noted in only 18 per cent of infants with rubella, and principally in those who had the more severe and usually clinically recognized manifestations of congenital rubella. Immunoglobulin values in sera collected during the first 6 months of life were elevated in approximately half of the infants tested and in those with mild illness as commonly as those with severe illness.