title: Biological characterization of a simian immunodeficiency virus-like retrovirus (HTLV-IV): evidence for CD4-associated molecules required for infection.
abstract: We have analyzed a number of biological features of HTLV-IV, a retrovirus indistinguishable from a macaque isolate of simian immunodeficiency virus (SIV), and compared this virus with several strains of human immunodeficiency virus type 1 (HIV-1). Although HTLV-IV was found to be similar to HIV-1 in its tropism for CD4+ lymphocytes, its effects on CD4 expression and the ability of its externalized envelope molecule to form a complex directly with the CD4 molecule, a number of striking differences were noted. Unlike with HIV-1, the range of cells susceptible to HTLV-IV infection and syncytia formation was restricted to a subset of CD4+ cell lines, particularly those that coexpressed CD4 with human leukocyte antigen (HLA) class II antigens. An analysis of the patterns of HTLV-IV infection with B x T somatic cell hybrids indicated that for this virus, molecules in addition to CD4 were probably required to facilitate infection and cell fusion. Additional studies of HTLV-IV infection of Sup-T1 cells, which are exquisitely sensitive to cytopathic effects induced by HIV-1, demonstrated that HTLV-IV infection could occur in the absence of cytopathic effects and, remarkably, with minimal or no downmodulation of the CD4 molecule from the cell surface. The failure of HTLV-IV infection to reduce the expression of several CD4 epitopes suggested that the HTLV-IV envelope produced by Sup-T1 cells was altered in its ability to interact with or bind to CD4. Additional differences were also noted in the size of the transmembrane envelope molecule of HTLV-IV produced by Sup-T1 cells, indicating that cell-specific alterations in processing of the HTLV-IV envelope occurred during the production of virus in this cell line. Understanding the basis for these biological differences between HTLV-IV and the HIV-1 viruses may help to elucidate more general mechanisms for pathogenesis of other members of the SIV and HIV families of retroviruses.
authors.affiliation: Hematology-Oncology Section, Hospital of the University of Pennsylvania, Philadelphia 19104.
authors.forename: J A
authors.initials: JA
authors.lastname: Hoxie
authors.forename: B S
authors.initials: BS
authors.lastname: Haggarty
authors.forename: S E
authors.initials: SE
authors.lastname: Bonser
authors.forename: J L
authors.initials: JL
authors.lastname: Rackowski
authors.forename: H
authors.initials: H
authors.lastname: Shan
authors.forename: P J
authors.initials: PJ
authors.lastname: Kanki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D002459:Cell Fusion; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D017977:Deltaretrovirus / Q000502:physiology*; D006678:HIV / Q000502:physiology; D006681:HLA-D Antigens / Q000032:analysis; D000882:Haplorhini / Q000382:microbiology; D006801:Humans; D011991:Receptors, Virus / Q000502:physiology*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000382:microbiology*; D014759:Viral Envelope Proteins / Q000502:physiology; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D006681:HLA-D Antigens; D011991:Receptors, Virus; D014759:Viral Envelope Proteins