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Modification of cell tropism of HIV-1 by a single point mutation at the neutralization epitope in the env gene.


Int Conf AIDS. 1990 Jun 20-23;6(3):96 (abstract no. S.A.3). Unique

OBJECTIVE: We have isolated a variant of HIV-1 which is highly infectious to fibroblast-like cells (BT cells) derived from human brain as well as CD4 positive T cells. This variant HIV-1, named HIV[GUN-1v], was obtained by infecting BT cells with a proto-type HIV-1 isolate, named HIV[GUN]1wt], which is highly infectious to T cells, but scarcely infectious to BT cells. The viral gene responsible for the host-range difference between the variant and proto-type HIV-1s was tried to be elucidated. METHODS: Various chimeric recombinant viruses were made and examined their host range. The restriction fragments responsible for the difference in the host-range and DNA sequences of these fragments were determined. Site-directed mutagenesis was used to confirm the base substitutions which were responsible for the host ranges of the HIV isolates. RESULTS: Examination of the infectivities of various recombinant viruses and mutagenized viruses showed that a single nucleotide exchange was responsible for the difference in infectivity of BT cells: HIV[GUN-1v] contains a thymine residue instead of the cytosine residue in HIV[GUN-1wt] at position 931 of the env coding sequence. This replacement in HIV[GUN-1wt] genome induced ability to infect BT cells, which was expected to change the 311th amino acid of the envelope glycoprotein, gp120, from proline to serine, that is located in a variable region containing type-specific immunodominant epitopes. CONCLUSION: HIV[GUN-1v] acquired a wider host range than HIV[GUN-1wt] by a single point mutation in the type-specific neutralization epitope of the env gene.

Brain/MICROBIOLOGY Cells, Cultured Chimera Cloning, Molecular CD4-Positive T-Lymphocytes/MICROBIOLOGY DNA, Viral/ANALYSIS Epitopes/*GENETICS Human HIV Envelope Protein gp120/GENETICS/IMMUNOLOGY HIV-1/*GENETICS/IMMUNOLOGY/ISOLATION & PURIF *Mutation Neutralization Tests Restriction Mapping ABSTRACT


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