The human immunodeficiency virus (HIV) gag gene product p18 is responsible for enhanced fusogenicity and host range tropism of the highly cytopathic HIV-1-NDK strain.
Formation of large syncytia and rapid cell killing are characteristics of the Zairian human immunodeficiency virus type 1 isolate HIV-1-NDK, which is highly cytopathic for CD4+ lymphocytes in comparison with the HIV-1-LAV prototype. Chimeric viruses containing different combinations of HIV-1-NDK genetic determinants corresponding to the splice donor, the packaging signal, and the coding sequence of the p18gag protein together with the HIV-1-NDK EcoRI5278-XhoI8401 fragment were obtained by polymerase chain reaction-directed recombination. Phenotypic analysis of recombinant viruses indicated that 75 amino acids from the N-terminal part of HIV-1-NDK p18gag protein together with the HIV-1-NDK envelope glycoprotein are responsible for enhanced fusogenicity of HIV-1-NDK in CD4+ lymphocytes as well as for enhanced infectivity of HIV-1-NDK in some CD4- cells lines. The HIV-1-NDK splice donor/packaging sequence and the sequence encoding the gag protein p25 were not important for the variation observed in HIV-1 fusogenicity.
INSERM U322, Unité de Recherches sur les Rétrovirus et Maladies Associées, Campus Universitaire de Luminy, Marseille, France.
J
J
de Mareuil
B
B
Brichacek
D
D
Salaun
J C
JC
Chermann
I
I
Hirsch
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology; D002459:Cell Fusion / Q000235:genetics; D015023:Democratic Republic of the Congo; D015683:Gene Products, gag / Q000235:genetics*; D005814:Genes, Viral; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011994:Recombinant Proteins; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014760:Viral Fusion Proteins / Q000235:genetics*; D014774:Virulence; D014779:Virus Replication / Q000235:genetics; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D011994:Recombinant Proteins; D014760:Viral Fusion Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C061169:p18 gag protein, Human immunodeficiency virus 1