CD4-independent infection of human peripheral blood dendritic cells with isolates of human immunodeficiency virus type 1

• Published in: Journal of general virology 1993-07, Vol.74 (7), p.1277-1285
• Main Authors: Chehimi, Jihed, Prakash, Kesh, Shanmugam, Vedapuri, Collman, Ronald, Jackson, Stephanie J, Bandyopadhyay, Santu, Starr, Stuart E
• Format: Article
• Language: English
• Subjects: Adult; AIDS/HIV; Antigens, CD - biosynthesis; Antigens, CD - genetics; Antigens, CD - physiology; Base Sequence; Biological and medical sciences; Blotting, Northern; Blotting, Southern; CD4 Antigens - biosynthesis; CD4 Antigens - genetics; CD4 Antigens - physiology; Dendritic Cells - microbiology; DNA, Viral - analysis; Fundamental and applied biological sciences. Psychology; HIV Core Protein p24 - analysis; HIV Core Protein p24 - biosynthesis; HIV-1 - isolation & purification; HIV-1 - physiology; human immunodeficiency virus 1; Humans; Microbiology; Molecular Sequence Data; Oligodeoxyribonucleotides; Polymerase Chain Reaction; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; RNA, Viral - analysis; Species Specificity; Virology; Virus Replication
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-74-7-1277

1 Division of Allergy, Immunology and Infectious Diseases, The Joseph Stokes Jr Research Institute of The Children's Hospital of Philadelphia and 2 Division of Pulmonary and Intensive Care, The Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, U.S.A. Dendritic cells (DC) are members of a distinct family of bone marrow-derived leukocytes. DC are potent accessory cells for a number of T cell-mediated immune responses, including autologous and allogeneic mixed leukocyte reactions, and mitogen- and antigen-stimulated lymphocyte proliferation. In the present study, DC purified from human peripheral blood were inoculated with various strains (IIIB, SF2, WMJ1, SF162, 89.6 and clone HXB2) of human immunodeficiency virus type 1 (HIV-1) displaying different patterns of cellular tropism. Viral replication was demonstrated by detection of p24 antigen (Ag) intracellularly and in culture supernatants, and by Southern and Northern blot analyses for the presence of HIV DNA and RNA, respectively, within infected cells. Cell-free and cell-associated p24 Ag levels rose substantially when DC were inoculated with strains SF162, 89.6 and clone HXB2. In contrast, p24 Ag levels rose only marginally after inoculation of DC with strains IIIB, SF2 and WMJ1. Purified DC did not express detectable membrane CD4, although CD4 mRNA was detected by reverse transcriptase PCR. The presence of anti-CD4 monoclonal antibodies failed to block infection of DC by any of the HIV strains tested, suggesting the existence of a CD4-independent alternative pathway of viral entry. The possibility that DC serve as a reservoir for HIV-1 must be considered. Present address: Ortho Diagnostic Systems, Inc., Raritan, New Jersey 08869, U.S.A. Present address: Morehouse School of Medicine, Department of Pathology, Atlanta, Georgia 30310, U.S.A. Present address: The Indian Institute of Chemical Biology, Calcutta, India. Received 13 November 1992; accepted 18 February 1993.