Efficient HIV-1 replication can occur in the absence of the viral matrix protein.
Matrix (MA), a major structural protein of retroviruses, is thought to play a critical role in several steps of the HIV-1 replication cycle, including the plasma membrane targeting of Gag, the incorporation of envelope (Env) glycoproteins into nascent particles, and the nuclear import of the viral genome in non-dividing cells. We now show that the entire MA protein is dispensable for the incorporation of HIV-1 Env glycoproteins with a shortened cytoplasmic domain. Furthermore, efficient HIV-1 replication in the absence of up to 90% of MA was observed in a cell line in which the cytoplasmic domain of Env is not required. Additional compensatory changes in Gag permitted efficient virus replication even if all of MA was replaced by a heterologous membrane targeting signal. Viruses which lacked the globular domain of MA but retained its N-terminal myristyl anchor exhibited an increased ability to form both extracellular and intracellular virus particles, consistent with a myristyl switch model of Gag membrane targeting. Pseudotyped HIV-1 particles that lacked the structurally conserved globular head of MA efficiently infected macrophages, indicating that MA is dispensable for nuclear import in terminally differentiated cells.
Reil
H
H
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Bukovsky
A A
AA
Gelderblom
H R
HR
Göttlinger
H G
HG
D001483:Base Sequence; D002460:Cell Line; D015686:Gene Products, env / Q000096:biosynthesis; D016336:Gene Products, vpr / Q000096:biosynthesis; D015752:Genes, env; D005816:Genetic Complementation Test; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D011533:Proviruses / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014763:Viral Matrix Proteins / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D016336:Gene Products, vpr; D016655:HIV Core Protein p24; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus