Prolonged Shedding of Amantadine-Resistant Influenza A Viruses by Immunodeficient Patients: Detection by Polymerase Chain Reaction-Restriction Analysis

Consecutive A (H3N2) influenza virus isolates from 2 influenza virus-infected immunodeficient patients treated with amantadine were examined using a novel polymerase chain reaction (PCR)-restriction analysis for resistance to this antiviral compound. The data indicate that immunodeficient patients may shed resistant viruses for prolonged periods and with different drug resistance muta-tions present at different times. This PCR-restriction technique allows rapid detection of amanta-dine- or rimantadine-resistant strains. Amantadine and rimantadine specifically inhibit influenza A virus infection by targeting the hydrophobic transmembrane domain of the M2 protein [1]. The 97-amino acid-long M2 protein molecules form membrane-spanning tetramers, which have ion channel activity and regulate vesicular and cyto-plasmic pH within the virus-infected cells. Amantadine and rimantadine interact with these channels [1]. Resistant mutants arise readily after the virus is grown in embryonated eggs, tissue culture, or animals in the presence o