Impaired humoral responses to subgenus D adenovirusenovirus infections in HIV-positive patients

HIV-positive patients are at increased risk of developing adenovirus infect ion, particularly of the gastrointestinal tract and with unusual subgenus D strains. To investigate humoral immunity to these strains of adenoviruses, the humoral immune response was examined in longitudinal samples of serum against isolates collected from a prospective study of HIV-positive patient s with subgenus D adenovirus infection. Of 10 HIV-positive patients develop ing adenovirus infection, 3 had chronic infection (8-->27 months) with one serotype, 3 had chronic infection (greater than or equal to 10 months) with changing serotypes and 4 had acute and self-limiting adenovirus infection (<1 month). Fifty-one sera were tested, and samples collected before adenov irus infection were available in 8 patients. Neutralising assays were perfo rmed against the patient's own isolate (adenoviruses 9, 17, 19, 19/23, 19/3 7, 23, 26, 23/26, 43 and 46) and common circulating strains of adenovirus 1 -5. Indirect immunofluorescence tests were carried out against the autologo us isolate and complement-fixation tests were undertaken using a standard a ssay. Immunofluorescence test antibodies were detected (titre <greater than or equal to>160) in all patients, and present to high titre (greater than or equal to 320) in 8/10 patients. Complement-fixing antibodies were not de tected in significant titre. Of particular note, there was no significant n eutralising antibody response to the patient's own isolate after acute infe ction. Neutralising antibody to adenovirus 3 (titre 20) was transiently det ected in two patients. In the remaining patients neutralising antibody dire cted against adenoviruses 1-5 was not detected. Persistent carriage of subg enus D adenoviruses in HIV-positive patients is probably the result of fail ure of cell-mediated immune responses to clear primary infection. Neverthel ess, there is marked impairment of B cell responses resulting in poor neutr alising and complement-fixing antibody production even though immunofluores cence test determined antibodies are produced in high titre. These possibly reflect impairment of effective B cell priming mechanisms within the germi nal centres of lymph nodes, or the polyclonal activation of B cells driven by HIV infection. J. Med. Virol. 62: 405-409, 2000. (C) 2000 Wiley-Liss, In c.