To study the antigenic characteristics of respiratory syncytial virus (RSV), we developed and evaluated monoclonal antibodies (MAbs) to three strains of RSV: 11 to Long, 4 to 18537, and 9 to A2. Six of these MAbs immunoprecipitated the nucleoprotein, six the large glycoprotein, and 11 the fusion protein. By the pattern of the reactions of these MAbs to 16 strains of RSV in an indirect immunofluorescence assay or enzyme-linked immunosorbent assay, we were able to distinguish three subgroups. With a panel of 10 of these 24 MAbs, we tested 26 strains isolated between 1979 and 1982 in Boston and found that 22 belonged to group 1, 4 to group 2, and none to group 3. The pattern of the reactions of the MAbs against representative strains from the three groups identified nine epitopes by indirect immunofluorescence assay: three of each on the nucleoprotein, the large glycoprotein, and the fusion protein. These results, along with those of previous studies, suggest that groups 1 and 3 are antigenically similar and group 2 is antigenically more distinct.
Adenoviruses are among the many pathogens and opportunistic agents that cause serious infection in the congenitally immunocompromised, in patients undergoing immunosuppressive treatment for organ and tissue transplants and for cancers, and in human immunodeficiency virus-infected patients. Adenovirus infections in these patients tend to become disseminated and severe, and the serotypes involved are clustered according to the age of the patient and the nature of the immunosuppression. Over 300 adenovirus infections in immunocompromised patients, with an overall case fatality rate of 48%, are reviewed in this paper. Children with severe combined immunodeficiency syndrome and other primary immunodeficiencies are exposed to the serotypes of subgroups B and C that commonly infect young children, and thus their infections are due to types 1 to 7 and 31 of subgenus A. Children with bone marrow and liver transplants often have lung and liver adenovirus infections that are due to an expanded set of subgenus A, B, C, and E serotypes. Adults with kidney transplants have viruses of subgenus B, mostly types 11, 34, and 35, which cause cystitis. This review indicates that 11% of transplant recipients become infected with adenoviruses, with case fatality rates from 60% for bone marrow transplant patients to 18% for renal transplant patients. Patients with AIDS become infected with a diversity of serotypes of all subgenera because their adult age and life-style expose them to many adenoviruses, possibly resulting in antigenically intermediate strains that are not found elsewhere. Interestingly, isolates from the urine of AIDS patients are generally of subgenus B and comprise types 11, 21, 34, 35, and intermediate strains of these types, whereas isolates from stool are of subgenus D and comprise many rare, new, and intermediate strains that are untypeable for practical purposes. It has been estimated that adenoviruses cause active infection in 12% of AIDS patients and that 45% of these infections terminate in death within 2 months. In all immunocompromised patients, generalized illness involving the central nervous system, respiratory system, hepatitis, and gastroenteritis usually have a fulminant course and result in death. Treatments for adenovirus infections are of little proven value, although certain purine and pyrimidine analogs have shown beneficial effects in vitro and may be promising drugs.
DNA restriction patterns of all known human adenovirus prototypes (1 to 41), ordered according to subgenera A to F, are presented for restriction endonucleases BamHI, BglII, BstEII, HindIII, and SmaI. This catalogue is a prerequisite for typing of adenoviruses by DNA restriction analysis in diagnostic laboratories and for strain identification in reference laboratories. To determine the genetic relationship of human adenoviruses within a subgenus and between subgenera, a pairwise analysis of comigrating fragments was performed. Adenoviruses of subgenus C were closely related. Adenoviruses of subgenus B showed two related clusters of four types each, whereas the numerous serotypes of subgenus D did not show any corresponding clustering. Little comigration was observed between DNA restriction fragments from members of subgenus A or F respectively.
We analyzed 67 adenovirus isolates from 48 patients with AIDS. The isolates included 5 of subgenus A (all Ad31), 23 of subgenus B, 4 of subgenus C (all Ad5), and 35 of subgenus D. The subgenus A and C strains were from liver, lung, blood, urine, and stool and were unremarkable in their antigenic characteristics. The subgenus B strains were mostly from urine and were serotyped by neutralization (SN) and hemagglutination-inhibition (HAI) tests as Ad11 (12 isolates), Ad16 (1), Ad35 (3), and Ad21/H21 + 35 (1) plus new intermediate strains 34/H11 (3), 35/H11 (1), and 11 + 35/H11 (2). The subgenus D serotypes from 24 patients were mostly from stool specimens and consisted of 8 isolates of known serotypes, 16 of antigenically intermediate strains, and 11 of five new adenovirus types with distinct antigenic and restriction enzyme characteristics. The new serotypes were described as candidate types 43-47 in accordance with currently accepted taxonomic criteria. Ad45, 46, and 47 showed a major relation by HAI with Ad29, 24, and 20, respectively. Four intermediate types were related to the new serotypes. The plethora of serotypes from patients with AIDS suggests that no epidemiological significance can be attached to any one serotype.
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