EFFICIENT PARTICLE FORMATION CAN OCCUR IF THE MATRIX DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GAG IS SUBSTITUTED BY A MYRISTYLATION SIGNAL

Lentiviruses, such as human immunodeficiency virus type 1 (HIV-1), ass emble at and bud through the cytoplasmic membrane. Both the matrix (MA ) domain of Gag and its amino-terminal myristylation have been implica ted in these processes. We have created HIV-1 proviruses lacking the e ntire matrix domain of gag which either lack or contain an amino-termi nal myristate addition sequence at the beginning of the capsid domain. Myristate- and matrix-deficient [myr(-)MA(-)] viruses produced after transient transfection are still able to assemble into particles, alth ough the majority do not form at the plasma membrane or bud efficientl y. Myristylation of the amino terminus of the truncated Gag precursor permits a much more efficient release of the mutant virions. While myr (-)MA(-) particles were inefficient in proteolytic processing of the G ag precursor, myristylation enabled efficient proteolysis of the mutan t Gag. All matrix-deficient viruses are noninfectious. Particles produ ced by matrix-deficient mutants contain low levels of glycoproteins, i ndicating the importance of matrix in either incorporation or stable r etention of Env. Since matrix-deficient viruses contain a normal compl ement of viral genomic RNA, a role for MA in genomic incorporation can be excluded. Contrary to previous reports, the HIV-1 genome does not require sequences between the 5' splice donor site and the gag start c odon for efficient packaging.