Single amino acid changes in the human immunodeficiency virus type 1 matrix protein block virus particle production.
The matrix protein of human immunodeficiency virus type 1 is encoded by the amino-terminal portion of the Gag precursor and is postulated to be involved in a variety of functions in the virus life cycle. To define domains and specific amino acid residues of the matrix protein that are involved in virus particle assembly, we introduced 35 amino acid substitution mutations in the human immunodeficiency virus type 1 matrix protein. Using reverse transcriptase and radioimmunoprecipitation analyses and transmission electron microscopy, we assessed the mutants for their ability to form virus particles and to function in the infection process. This study has identified several domains of the matrix protein in which single amino acid substitutions dramatically reduce the efficiency of virus particle production. These domains include the six amino-terminal residues of matrix, the region of matrix between amino acids 55 and 59, and the region between amino acids 84 and 95. Single amino acid substitutions in one of these domains (between matrix amino acids 84 and 88) result in a redirection of the majority of virus particle formation to sites within cytoplasmic vacuoles.
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
E O
EO
Freed
J M
JM
Orenstein
A J
AJ
Buckler-White
M A
MA
Martin
D000595:Amino Acid Sequence; D002460:Cell Line; D015683:Gene Products, gag / Q000737:chemistry* / Q000502:physiology; D015488:HIV Antigens / Q000737:chemistry* / Q000502:physiology; D015497:HIV-1 / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011498:Protein Precursors / Q000737:chemistry; D015531:Radioimmunoprecipitation Assay; D014764:Viral Proteins; D014779:Virus Replication / Q000502:physiology; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015488:HIV Antigens; D011498:Protein Precursors; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1