Y Oshima

Compatibility of Vpu-like activity in the four groups of primate immunodeficiency viruses.

Env-minus mutants of the viruses of major four human and simian immunodeficiency viruses (HIVs and SIVs) were monitored for their progeny virion production upon transfection into the cells, which are dependent on the HIV-1 Vpu for efficient particle release. Of the env mutants of HIV-1 (one mutant), HIV-2/SIVmac (three mutants), SIVagm (one mutant), and SIVmnd (one mutant) examined, the mutant of SIVmnd generated a very low level of progeny virions similar to that by the HIV-1 Vpu-minus mutant. This effect of the mutation was not observed in the cells which are independent on the Vpu for virion release. The Env of SIVmnd efficiently enhanced virion release of heterologous viruses like the HIV-1 Vpu.

Inhibition of HIV/SIV replication by dominant negative Gag mutants.

There are several major strategies against HIV/AIDS. Of these, the gene therapy is a novel, challenging, and promising one. The target genes, which have been extensively studied for the potential gene therapy of HIV/AIDS, include those of cellular and viral origins. Especially, trans-dominant negative Tat, Rev, Env, Pol, and Gag mutants of HIV have currently attracted considerable attention. In this brief review, we summarize the nature of the HIV/SIV mutants of this category and discuss their future use for gene therapy with special reference to the dominant negative Gag mutants of HIV-1.

Cell-dependent replication potentials of HIV-1 gag mutants

An infectious molecular clone of human immunodeficiency virus type 1 (HIV-1), designated pNLaiKH, which is tropic for both lymphocytic and monocytic cells, was constructed. To study the early function of HIV-1 Gag proteins in two types of cells, the mutations known to give host cell-dependent early defects were introduced into pNLaiKH, and the replication potentials and defective replication sites in the cells of the resultant mutants were monitored. All mutants grew in some lymphocytic cells, but not at all in monocytic cells. A nucleocapsid mutant was found to be defective at an early replication phase in all the cell lines to various extent, as expected. In contrast, a matrix mutant and a capsid mutant displayed a replication defect in a producer-cell-dependent manner. These results demonstrated that complex interactions of cell factors and Gag proteins are involved in an early process of HIV-1 replication.