The Role of Gag in Human Immunodeficiency Virus Type 1 Virion Morphogenesis and Early Steps of the Viral Life Cycle

The phenotypes of a series of mutant human immunodeficiency virus type 1 proviruses with linker insertion and deletion mutations within the gag coding region were characterized. These mutants, with mutations in the matrix, capsid, and p2 coding regions, produced replication-defective virion particles with defects in the early steps of the viral life cycle. To investigate this phenotype further, the abilities of mutant virion particles to enter T cells, initiate and complete reverse transcription, and transport the newly transcribed proviral DNA were investigated. Only 4 of 10 of the mutants appeared to make wild-type levels of viral DNA. Biochemical analyses of the mutants revealed the middle region of CA as being important in determining virion particle density and sedimentation in velocity gradients. This region also appears to be critical in determining the morphology of mature virion particles by electron microscopy. Particles with aberrant morphology were uninfectious, and only those mutants which displayed cone-shaped cores were capable of carrying out the early steps of the viral life cycle. Thus, the normal morphology of human immunodeficiency virus type 1 appears to be critical to infectivity.