Analysis of antigenically intermediate strains of subgenus B and D adenoviruses from AIDS patients

Abstract

We carried out detailed antigenic and restriction enzyme (RE) analyses on the subgenus B and D adenovirus isolates from 48 AIDS patients. These isolates were unusual both in the diversity of serotypes and in the number of intermediate strains identified. All unusual isolates were strain-purified and tested by serum neutralization (SN) and hemagglutination-inhibition (HI) tests with reference horse and rabbit antisera to all the prototype human adenoviruses; conversely, rabbit antisera were prepared to 16 selected strains from this study and tested by SN and HI with all prototype viruses. Among subgenus B strains, 6 DNA variants of Ad 11 isolates were distinguished by endonucleases BamHI, BglII, BstEII, HindIII, and SmaI. The D 2 variant of Ad 11 was prominent with 5 isolates, and 7 other isolates differed from D 2 in only 1 or 2 enzymes. HindIII was the most discriminative endonuclease for Ad 11 and related strains. Within subgenus D, there were 16 isolates of intermediate strains, including 4 intermediate types related to new Ad types 43-47. The RE patterns of subgenus D strains showed fragment distributions typical of subgenus D, with various unique patterns. Particular care was taken to analyze multiple strains from the same patient, recovered as much as 8 months apart, for evidence of genetic changes. The possible long-term infections with these viruses may provide the opportunity for mutations and recombination to occur, with the resultant generation of a variety of new strains of adenoviruses.

Two New Candidate Adenovirus Serotypes

“…Based on the serologic crossre actions, hemagglutination of rat but not monkey erythrocytes and the numbers of DNA frag ments with different restriction endonucleases, AV 48 and 49 are members of AV subgenus D. 82 Schnurr/Dondero Two New Adenovirus Types Similar to the AV 43-47 serotypes described by Hierholzer et al [10], most isolates of AV 48 and 49 were from cases of AIDS. As has also been previously observed for AVs from AIDS cases [12,13] there were a number of intermedi ate types of AV 48 and 49. The suggestion by Hierholzer [14] that new AV serotypes may be isolated from AIDS patients either because persistent infection in the immunocom promised host may provide an ideal environ ment for genetic interaction among AVs allow ing for new serotypes to appear, or a newly recognized serotype may be more likely to cause symptoms in and thus be isolated from an immunocompromised person is consistent with the association of these new serotypes with AIDS patients.…”

Adenoviruses in the immunocompromised host

“…This is in marked contrast to the 23 serotypes and 14 different intermediate strains reported from AIDS patients (17,19,25,30,42,45,49,51,53,57,71,119,133).…”

“…The DNA is then cut into fragments that are 4 to 7 nucleotides long, depending on the endonuclease used, and the fragments are separated by gel electrophoresis, stained with ethidium bromide, and visualized under UV light. A large selection of endonucleases derived from various bacteria and fungi are now available, and most studies employ 6 to 10 enzymes to show genome variant groupings and relationships among strains (2,13,25,27,36,43,45,49,52,53,60,103,120,121,126,127,132 (2,43,52,104,127,134,135). Most illnesses are self-limiting within 2 weeks and induce typespecific immunity.…”

Development and Assessment of Human Adenovirus Type 11 as a Gene Transfer Vector

“…First, the amino acid sequences of B group Ad fiber knobs are highly divergent (63). Second, although Ad11 is typically associated with kidney and urinary tract infections and is commonly found in immunocompromised patients (18,19,72), unlike Ad35, it has also been associated with both respiratory infections and conjunctivitis (1,24). Third, radiolabeled Ad11a and Ad11p demonstrate different levels of attachment to a number of human cell lines (35).…”