Host range mutant of human immunodeficiency virus type 1: modification of cell tropism by a single point mutation at the neutralization epitope in the env gene.

We have isolated a variant of human immunodeficiency virus type 1 (HIV-1) which is highly infectious to fibroblastlike cells (BT cells) derived from human brain as well as CD4-positive T cells. This variant HIV-1, named HIVGUN-1V], was obtained by infecting BT cells with a prototype HIV-1 isolate, named HIVGUN-1WT], which is highly infectious to T cells but barely infectious to BT cells. HIVGUN-1V] infects BT cells productively and this infection appeared to be mediated by CD4. To elucidate the viral gene responsible for the host range difference between the variant and prototype HIV-1s, we cloned and analyzed the provirus genomes of the two viruses. Examination of the infectivities of BT cells by various recombinant viruses and analyses of the nucleotide sequences of HIVGUN-1V] and HIVGUN-1WT] showed that a single nucleotide exchange was responsible for their difference in infectivity of BT cells: HIVGUN-1V] contains a thymine residue instead of the cytosine residue in HIVGUN-1WT] at position 931 of the env coding sequence. Replacement of cytosine by thymine at this position of the env coding sequence of the HIVGUN-1WT] genome induced the ability to infect BT cells. The base exchange at this position was expected to change amino acid 311 of the envelope glycoprotein, gp120, from proline to serine, which is located in a variable region containing type-specific immunodominant epitopes. Thus, HIVGUN-1V] acquired a wider host range than HIVGUN-1WT] by a single point mutation in the env gene.