Document 0417 DOCN M9590417 TI Fusogenic determinants of highly cytopathic subtype D Zairian isolate HIV-1 NDK. DT 9509 AU De Mareuil J; Salaun D; Chermann JC; Hirsch I; Unite de Recherches sur les Retrovirus et Maladies Associees,; INSERM U322, Parc Scientifique et Technologique de Luminy,; Marseille, France. SO Virology. 1995 Jun 1;209(2):649-53. Unique Identifier : AIDSLINE MED/95297167 AB Phenotypic characterization of subtype B strains of human immunodeficiency virus type 1 (HIV-1) indicates that the major determinants of their cytopathogenicity and tropism are contained in the gene coding for the envelope glycoprotein gp120, namely in its variable regions V1, V2, and V3. Recombinant viruses derived from HIV-1 LAV, the subtype B prototype virus, and HIV-1 NDK, the Zairian subtype D virus highly cytopathic for CD4-positive lymphocytes, were used to elucidate genetic control of fusogenic functions in subtype D viruses. Our data demonstrate that multigenic determination of fusogenic properties is more complex in the subtype D than in clade B viruses. Variability in three regions of HIV-1 NDK genome correlated with formation of large syncytia. These regions consisted of the matrix protein, the C-terminal portion of vpr up to the C1 region of gp120, and the V1-V3 regions of gp120. Variability in the envelope glycoprotein but not in other regions of the HIV-1 genome was related to enhanced resistance of HIV-1 NDK to treatment of target cells with OKT4-A anti-CD4 MAb. Therefore, a different genetic control affects two aspects of HIV-1 fusogenicity: (i) variability in the envelope glycoprotein itself is sufficient to influence a virus-to-cell fusion at the virus/cell entry, and (ii) a more complex genetic function including genes of matrix protein and envelope glycoprotein is related to variability of cell-to-cell fusion during formation of syncytium. DE Antibodies, Monoclonal/PHARMACOLOGY Comparative Study CD4-Positive T-Lymphocytes/*VIROLOGY DNA Replication Genes, Viral Genome, Viral Human HIV Envelope Protein gp120/BIOSYNTHESIS/GENETICS HIV-1/ISOLATION & PURIF/*PHYSIOLOGY/*PATHOGENICITY Membrane Fusion Recombination, Genetic Restriction Mapping Support, Non-U.S. Gov't Virus Replication Zaire JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).