Cyclophilin A-independent replication of a human immunodeficiency virus type 1 isolate carrying a small portion of the simian immunodeficiency virus SIV(MAC)gag capsid region

Hybrid viruses between human immunodeficiency virus type 1 (HIV-1) and simi an immunodeficiency virus strain mac (SIVMAC) are invaluable to various fie lds of HIV-1 research. To date, however, no replication-competent HIV-1 str ain containing the gag capsid (CA) region of SIVMAC has been reported. To o btain the viable gag gene chimeric virus in an HIV-1 background, seven HIV- 1 strains carrying a part of SIVMAC CA or a small deletion in the CA region were constructed and examined for their biological and biochemical charact eristics. While all the recombinants and mutants were found to express Gag and to produce progeny virions on transfection, only one chimeric virus, wh ich has 18 bp of SIV gag CA sequence in place of the region encoding the HI V-1 CA cyclophilin A (CyPA)-binding loop, was infectious for human cell lin es. Although this chimeric virus was unable to grow in monkey lymphocytic c ells like wild-type (wt) HIV-1 did, it grew much better than wt virus in th e presence of cyclosporin A in a human cell line which supports HIV-1 repli cation in a CyPA-dependent manner. These results indicate that the transfer of a small portion of the SIVMAC CA region to HIV-1 could confer the CyPA- independent replication potential of SIVMAC on the virus.