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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



 




Information in this article was accurate in December 30, 1990. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.