Excretion of human immunodeficiency type 1 in the throat but not in urine by infected children.
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Biomedical subjects
Publications and source records attributed to S A Plotkin.
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Clonal lines of human rhabdomyosarcoma (RD) cells, constitutively expressing human immunodeficiency virus type 1 (HIV-1) tat gene (RD tat cell lines) showed enhanced expression of human cytomegalovirus (HCMV) immediate-early (IE) and late (L) proteins upon HCMV infection, as compared with control RD cells. One of the RD tat cell lines produced infectious HCMV. The RD-tat cell lines, following transfection with recombinant plasmids containing the full length of the HCMV-IE enhancer/promoter linked to the bacterial chloramphenicol acetyltransferase (CAT) gene, exhibited an increased CAT expression by the tat product. A chronically HIV-1-infected human T-lymphoid cell line, SupT1, superinfected with HCMV, expressed HCMV-IE proteins while the parental SupT1 cells infected with HCMV were negative. Parental SupT1 cells coinfected with HIV-1 and HCMV also expressed HCMV-IE proteins, indicating that HIV-1-encoded proteins exert a positive regulatory effect on HCMV expression.
Although epidemic poliomyelitis in the United States has been eliminated, there are a number of current issues that concern the use of oral attenuated poliovirus vaccine in comparison with the new enhanced-potency inactivated vaccine. Although wild-type poliovirus is almost eradicated in developed nations, vaccine-induced polio exists, at a low but persistent rate. This article reviews the current issues and suggests a return to the Institute of Medicine's 1988 recommendations concerning combined immunization with inactivated poliovirus vaccine and oral poliovirus vaccine.
Human immunodeficiency virus (HIV) replicates in differentiated but not undifferentiated NTERA-2 human embryonal carcinoma cells; neither cell type expresses CD4. Susceptibility of the differentiated cells is enhanced by coinfection with cytomegalovirus. HIV infection induces lactoseries glycolipids, suggesting a mechanism whereby HIV might interfere with normal embryogenesis.
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Ordinarily, severe disease due to acquired cytomegalovirus (CMV) infection does not occur in immunocompetent children. We describe a previously healthy boy who acquired primary CMV infection at approximately 2 years of age and experienced a 2-year-long debilitating multisystem illness from which he ultimately recovered. Clinical features of this illness included fatigue, poor weight gain, pallor, unexplained fever, musculoskeletal complaints, drenching night sweats, lymphadenopathy, and massive hepatosplenomegaly. Laboratory abnormalities included elevated erythrocyte sedimentation rate, lymphocytosis, and elevated immune complex levels. Cellular immune function was impaired during the illness but was demonstrably normal during convalescence, and there was no other evidence for a known immunodeficiency state. Immunoblot analysis showed enhanced antibody response to a 66-kd infected cell protein after symptomatic recovery. Despite consistently normal indices of hepatic function, liver enlargement persisted after other symptoms had resolved. Liver biopsy demonstrated a mononuclear cell portal tract infiltrate with fibrosis, but CMV could not be demonstrated directly in this tissue. Primary CMV infection has not been reported previously to cause the persistent symptoms seen in this child.
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A reassortant rotavirus, strain W179-9, was constructed bearing gene 9 of serotype 1 rotavirus strain WI79 and all other genes derived from bovine (serotype 6) rotavirus strain WC3. The antigenic phenotype of WI79-9 is bivalent: serotype 1 and serotype 6. WI79-9 administered orally at a dose of 10(7.5) p.f.u. induced no adverse effects in 48 infants of age 2-11 months. Serotype 1- and serotype 6-specific serum neutralizing antibody titres were induced with approximately equal frequency in these infants. Serotype 1-specific antibody responses were inhibited in infants previously seropositive to type 1. The immune response rate was enhanced by administration of a second, 'booster dose'.
The safety and protective efficacy of a serotype 1 reassortant of bovine rotavirus WC3, disignated strain WI79-9, was evaluated in a double-blind placebo-controlled trial. Rotavirus reassortant WI79-9 contains a gene segment 9 coding for the surface structural protein vp7 of a human serotype 1 rotavirus, with all other gene segments derived from WC3 rotavirus, which had previously been shown to be safe and immunogenic in infants. Infants 2-11 months of age were given two doses of vaccine (10(7.3) plaque-forming units/dose) or of placebo 28 days apart. Adverse reactions to the vaccine were not detected. The incidence of serum plaque reduction neutralization antibody responses to two doses of vaccine was serotype 6, 97%; serotype 3, 68%; and serotype 1, 22%. Active surveillance during the subsequent rotavirus season revealed 8 cases of rotavirus gastroenteritis in 39 placebo control infants and no cases in 38 WI79-9 vaccine recipients (protection = 100%, P = .003). Six cases of rotavirus gastroenteritis were caused by type 1 and two by type 3 virus. Although vaccination with WI79-9 affected only the incidence of rotavirus gastroenteritis, the vaccinated infants exhibited a significantly reduced incidence of total days of diarrhea, fever, and illness associated with gastroenteritis in general.
The gene of the human cytomegalovirus (HCMV) major envelope glycoprotein, gB, was cloned from the Towne strain and inserted into adenovirus type 5 downstream of the E3 promoter. The recombinant virus, Ad-gB, expressed antigenically related proteins of 58, 30, 25, and 23 kDa in A549 and MRC-5 cells; the 58-kDa protein had the same mobility as the native gB from HCMV-infected MRC-5 cells and virions. All four proteins were detected by a monospecific polyclonal antiserum and by a monoclonal antibody in immunoblot and immunofluorescence assays. Hamsters infected intranasally with live Ad-gB developed protein-specific and HCMV-neutralizing antibody. This study confirms the importance of gB in the generation of the neutralizing immune response to HCMV and demonstrates the potential of live adenoviruses as vaccine vectors.
Biological interactions between human cytomegalovirus (HCMV) and the human immunodeficiency virus type 1 (HIV-1) were analysed in transfection and infection experiments, carried out in a human osteogenic sarcoma cell line (HOS) and in the same cell line chronically infected with HCMV (E155). When HOS and E155 cells were transfected with recombinant plasmids containing the HIV long terminal repeat (LTR) linked to the bacterial chloramphenicol acetyltransferase (CAT) gene, LTR-directed CAT expression was 20 times higher in E155 cells than in HOS cells. HOS cells co-infected with HCMV and HIV-1 showed enhanced production of the HIV-1 p24 antigen. In reciprocal experiments, an increase in HCMV immediate early gene expression was observed when HCMV-infected HOS cells and E155 cells were either transfected with a recombinant plasmid containing the HIV transactivator gene (pTAT), or when infected with HIV-1. DNA hybridization analysis of E155 and HCMV-infected HOS cells revealed higher levels of HCMV DNA in cells transfected with pTAT than in cells transfected with other non-specific recombinant plasmids. E155 cells transfected with pTAT also produced higher titres of infectious HCMV than control cultures of E155 cells transfected with other recombinant plasmids, including pMTAT carrying a mutant tat gene. The functional reciprocity in vitro between HCMV and HIV is discussed with respect to its possible implications for the clinical development of AIDS.
In recent years, data have been generated to support the view that cytomegalovirus (CMV) disease, which exacts a major toll on public health, will be amenable to vaccine immunoprophylaxis. Clinical trials have shown that a live attenuated CMV strain called Towne is both safe and immunogenic. Protection against CMV-induced disease with this vaccine appears to mimic that afforted by prior natural infection. Current research directed at the identification of molecular subunits retaining the immunogenic capacity of whole virus but lacking viral nucleic acid has yielded promising results. Target groups for a CMV vaccine will include patients with natural and iatrogenic forms of immunosuppression as well as seronegative women contemplating pregnancy.
A total of 44 children with acute lymphoblastic leukemia were immunized against chickenpox with the Oka/Merck strain live attenuated varicella vaccine. Of these children, 24 continued oral chemotherapy with 6-mercaptopurine during the immunization period and 20 had suspension of all chemotherapy for 1 week before and 1 week after the vaccine. Seroconversion, as determined by the detection of fluorescent antibody to membrane antigens, occurred in 91% and did not differ between patients continuing 6-mercaptopurine from those in whom chemotherapy was suspended. Fever and/or rash occurred in less than one third of vaccinated children. Unexpected reactions occurred in two vaccinated children, one from each group, both of whom had low absolute lymphocyte counts (less than 750/microL) on the day of immunization. Vaccine-induced immunity appeared effective in preventing or modifying chickenpox after exposure to natural disease.
In the spring and summer of 1988, two separate outbreaks of an illness with a rash resembling erythema infectiosum occurred among members of the nursing staff of the Children's Hospital of Philadelphia. The sources were two adolescent patients with sickle cell disease and aplastic crisis who had unsuspected parvovirus infection. Tests for IgM and IgG antibodies to parvovirus B19 were positive in both patients, and electron microscopical examination showed parvovirus-like particles in the early serum samples. Of 40 health care workers exposed to infected patients, 12 (30 percent) were infected, 2 (5 percent) were possibly infected, 8 (20 percent) had evidence of a past infection with B19, and 18 (45 percent) remained seronegative. Attack rates among the susceptible contacts were 36 percent in the first outbreak and at least 38 percent in the second. Clinical symptoms began a mean of 12.6 days after exposure and included malaise, rash, and joint pain. We conclude that hospital workers are at risk of contracting nosocomial erythema infectiosum from patients with parvovirus-associated aplastic crisis. We recommend that all patients with hereditary hemolytic anemias who are admitted with a febrile illness be evaluated for aplasia and promptly placed in respiratory and contact isolation if aplastic crisis is suspected.
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