Characterization of HIV1-PAR, a macrophage-tropic strain: cell tropism, virus/cell entry and nucleotide sequence of the envelope glycoprotein.
The HIV1-PAR strain, isolated from the cerebrospinal fluid of an HIV1-seropositive man suffering from encephalopathy, replicated well in cord blood lymphocytes, poorly in peripheral blood mononuclear cells, and to different levels in blood-derived macrophage (BDM) cultures prepared from different blood donors. In marked contrast to its replication in primocultures, it did not grow in CEM and U937 cell lines. HIV1-PAR production in BDM was inhibited by more than 90% after treatment with OKT4A or 13B8.2 monoclonal antibodies (mAb) binding to adjacent epitopes of the D1 domain of the CD4 molecules. A lower but significant inhibitory effect was observed after BDM treatment with BL4 and OKT4 mAb, directed to the D2 and D3 domain of the CD4 molecule, respectively. The entire HIV1-PAR envelope glycoprotein gene was amplified by polymerase chain reaction and sequenced. The deduced amino acid sequence of HIV1-PAR gp160 revealed the presence of 847 amino acids and 86% homology with the HIV1 LAV virus prototype. An alignment of the amino acid sequence of the envelope glycoprotein of HIV1-PAR and HIV1-LAV showed that the differences were mostly clustered within the five variable regions. Five CD4-binding domains, the gp120/gp41 cleavage site, the putative gp41 fusion domain and 21 out of the 22 cysteine residues were conserved in both isolates. The results further confirm the macrophage-tropic character of the HIV1-PAR virus.
Schmidtmayerova
H
H
Unité de Recherches INSERM U322 sur les Rétrovirus et Maladies Associées, Campus Universitaire de Luminy, Marseille, France.
Gayet
O
O
Guettari
N
N
Bolmont
C
C
Hirsch
I
I
Chermann
J C
JC
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents / Q000502:physiology*; D015704:CD4 Antigens / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D015686:Gene Products, env / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D019302:HIV Envelope Protein gp160; D006679:HIV Seropositivity / Q000134:cerebrospinal fluid; D015497:HIV-1 / Q000737:chemistry / Q000145:classification / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology*; D008297:Male; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015704:CD4 Antigens; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors