The non-producer phenotype of the human immunodeficiency virus type 1 provirus F12/HIV-1 is the result of multiple genetic variations.
A cell clone (Hut-78/F12) chronically infected with a non-producer human immunodeficiency virus type 1 (HIV-1) variant showed an abnormal pattern of virus structural proteins and released no detectable virus particles. Exchanges of homologous parts of the F12/HIV provirus and a replication-competent HIV (strain NL4-3) were undertaken to define the genetic determinants of the F12/HIV phenotype. The non-infectious phenotype was reproduced by replacing an NL4-3 genomic fragment encoding the C terminus of gp 120 and the N terminus of gp41 with the corresponding parts of the F12/HIV provirus. Conversely, a much more extended genomic fragment (encompassing the vif, pol and env genes) was necessary to convert the F12/HIV phenotype. These results demonstrate that the F12/HIV non-producer phenotype is the result of mutations scattered along most of the genome, rendering the conversion to an infectious phenotype a very unlikely event. The F12/HIV genome is thus a reliable model for preclinical studies of anti-HIV gene therapy.
Carlini
F
F
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Nicolini
A
A
d'Aloja
P
P
Federico
M
M
Verani
P
P
D003673:Defective Viruses / Q000235:genetics*; D015683:Gene Products, gag / Q000235:genetics; D014644:Genetic Variation; D015726:Giant Cells; D016655:HIV Core Protein p24 / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015700:HIV Envelope Protein gp41 / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D010641:Phenotype; D011533:Proviruses / Q000235:genetics; D014407:Tumor Cells, Cultured
D015683:Gene Products, gag; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D054303:HIV Reverse Transcriptase