Impaired Humoral Responses to Subgenus D Adenovirusenovirus Infections in HIV-positive Patients Alan Lord, 2 Andrew S. Bailey, 2 Paul E. Klapper, 2 Neil Snowden, 1 and Saye H. Khoo 1 * 1 The Departments of Infectious Diseases and Rheumatology, North Manchester General Hospital, Manchester, United Kingdom 2 Clinical Virology, Manchester Royal Infirmary, Manchester, United Kingdom HIV-positive patients are at increased risk of de- veloping adenovirus infection, particularly of the gastrointestinal tract and with unusual subge- nus 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 patients with subgenus D adenovirus infection. Of 10 HIV-positive patients developing adenovirus in- fection, 3 had chronic infection (8–>27 months) with one serotype, 3 had chronic infection (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 adenovirus infection were avail- able in 8 patients. Neutralising assays were per- formed against the patient’s own isolate (adeno- viruses 9, 17, 19, 19/23, 19/37, 23, 26, 23/26, 43 and 46) and common circulating strains of ad- enovirus 1–5. Indirect immunofluorescence tests were carried out against the autologous isolate and complement-fixation tests were undertaken using a standard assay. Immunofluorescence test antibodies were detected (titre 160) in all patients, and present to high titre (320) in 8/10 patients. Complement-fixing antibodies were not detected in significant titre. Of particular note, there was no significant neutralising anti- body response to the patient’s own isolate after acute infection. Neutralising antibody to adeno- virus 3 (titre 20) was transiently detected in two patients. In the remaining patients neutralising antibody directed against adenoviruses 1–5 was not detected. Persistent carriage of subgenus D adenoviruses in HIV-positive patients is prob- ably the result of failure of cell-mediated im- mune responses to clear primary infection. Nev- ertheless, there is marked impairment of B cell responses resulting in poor neutralising and complement-fixing antibody production even though immunofluorescence test determined antibodies are produced in high titre. These pos- sibly reflect impairment of effective B cell prim- ing mechanisms within the germinal centres of lymph nodes, or the polyclonal activation of B cells driven by HIV infection. J. Med. Virol. 62: 405–409, 2000. © 2000 Wiley-Liss, Inc. KEY WORDS: antibodies; opportunistic infec- tions; natural history; adenovi- rusenovirus INTRODUCTION Adenoviruses are double-stranded DNA viruses that are classified conventionally according to serotype (1– 49) and subgenus (A–F). Subgenus D adenoviruses are comparatively rare in immuno-competent individuals, with the exception of adenoviruses 10 and 19, that are associated with keratoconjunctivitis. HIV-positive patients at all stages of disease are at increased risk of acquiring adenovirus infection [Hier- holzer, 1992; Khoo et al., 1995]. These are character- ised by the isolation of ‘unusual’ subgenus B or D strains, typically from the gastrointestinal tract where by contrast, detection of common circulating strains of adenoviruses (e.g., adenovirus 1–5, 7, 31, 40, 41) is very rare. Indeed, all of the recently described subgenus D adenoviruses (adenovirus 43 onwards) were first iso- lated in AIDS patients. It was found previously that the actuarial risk of adenovirus infection in late-stage patients (CD 4+ count <200 cells/mm 3 ) was 38% at 1 year, and that although adenovirus infections may per- sist (2–27 months), they were asymptomatic or mini- mally symptomatic in over 50% patients [Khoo et al., 1995]. Nevertheless, adenoviruses are capable of pro- Contract grant sponsor: R.L. Gardner Memorial Bequest. *Correspondence to: Dr. S.H. Khoo, Department of Pharmacol- ogy, University of Liverpool, Ashton Street, Liverpool L69 3 BX, UK. E-mail: khoo@liverpool.ac.uk Accepted 24 January 2000 Journal of Medical Virology 62:405–409 (2000) © 2000 WILEY-LISS, INC.