Downregulation of cell surface molecules during noncytopathic infection of T cells with human immunodeficiency virus.
Noncytopathic infection of human T-lymphoid cell line CR-10 with human immunodeficiency virus (HIV) (CEM-N1T isolate) resulted in a gradual loss of cell surface receptors for OKT4/OKT4A (HIV receptor), OKT8, OKT3, and OKT11 but not for OKT9 (transferrin receptor) within 10 days after infection. Surface receptor decline was accompanied by a rapid increase in HIV antigens and mRNA expression. Multireceptor downregulation was also observed in three T-lymphoid cell lines (MT-4, CEM, and HBD-1) cytopathically infected with the HIV/N1T virus and in HUT-78 cells infected with the HIV/SF-2 isolate. HIV-infected and uninfected CR-10 cells contained similar levels of mRNAs coding for T3, T8, T9, T11, HLA-A2, and HLA-B7 proteins. By densitometry, fully infected CR-10 cells showed approximately 75% reduction in T4 and tubulin (beta chain) mRNA levels when compared with uninfected CR-10 cells. No such reduction was detected in HIV-infected MT-4 and HBD-1 cells. A T-cell receptor gene (beta chain) rearrangement study revealed that no distinct CR-10 subpopulation was selected out upon infection with HIV. Our results suggest that the reduction in cell surface receptors observed between 1 and 2 weeks postinfection cannot be directly attributed to similar reductions in mRNA levels coding for these receptor proteins. We conclude that HIV infection induces posttranscriptional downregulation of several T-cell surface receptors.
D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics*; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D005814:Genes, Viral; D006678:HIV / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015488:HIV Antigens; D006801:Humans; D007118:Immunoassay; D007700:Kinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics / Q000276:immunology; D011991:Receptors, Virus / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000382:microbiology*; D014158:Transcription, Genetic
D000954:Antigens, Surface; D000956:Antigens, Viral; D015488:HIV Antigens; D012333:RNA, Messenger; D012367:RNA, Viral; D011948:Receptors, Antigen, T-Cell; D011990:Receptors, Transferrin; D011991:Receptors, Virus