ABSTRACT
The adenovirus early region 3 glycoprotein E3-19k binds to and down regulates major histocompatibility complex (MHC) class I molecules in infected cells. We previously identified a 20-amino-acid conserved region in E3-19k by comparison of protein sequences from four different adenovirus serotypes. The roles of the E3-19k C-terminal and adjacent conserved regions in the interaction with MHC class I molecules have been examined. A functional class I-binding glycoprotein was expressed from the cloned E3 18.5-kDa open reading frame of adenovirus type 35. Truncations and single-amino-acid mutations in the adenovirus type 35 glycoprotein were created by site-directed in vitro mutagenesis and tested for the ability to associate with MHC class I molecules. Deletion of most of the transmembrane domain and cytoplasmic tail did not affect binding to class I molecules. However, removal of an additional 11 amino acids eliminated binding and changed the conformation of the adjacent conserved region. Separate mutations of residues Asp-107 and Met-110, within the conserved region, severely reduced or eliminated binding. These data indicate that the E3-19k conserved region plays a crucial role in binding to MHC class I molecules.
Subject(s)
Adenoviridae/genetics , Histocompatibility Antigens Class I/metabolism , Oncogene Proteins, Viral/genetics , Adenoviridae/immunology , Adenovirus Early Proteins , Amino Acid Sequence , Animals , Antigens, Viral, Tumor/genetics , Base Sequence , Blotting, Western , Cell Line , Molecular Sequence Data , Mutagenesis, Site-Directed , Oligodeoxyribonucleotides , Oncogene Proteins, Viral/immunology , Oncogene Proteins, Viral/metabolism , Open Reading Frames , Restriction Mapping , TransfectionABSTRACT
Five cases of large tuberculous abscesses in patients with AIDS were observed over a 2-year period at the New York Veterans Affairs Medical Center. These cases represent 11.6% of the 43 cases of tuberculosis diagnosed in patients with AIDS during that period. The abscesses were located in the liver, abdominal wall, psoas muscle, mediastinum, and peripancreatic area. All patients presented with localized pain or swelling, and four of five patients had fever. The diagnosis was made on the basis of detection of abscesses on computed tomography (CT) and the results of culture of abscess material obtained by CT-guided aspiration. CT-guided therapeutic drainage was performed in two cases. Despite administration of therapy, two of five patients died of tuberculous infection. Formation of tuberculous abscesses appears to be a common complication of tuberculosis in patients with AIDS. This diagnosis should be considered for patients with AIDS who have fever and localized pain or swelling.