Functional exchange of an oncoretrovirus and a lentivirus matrix protein.
To map functional domains in the retroviral Gag protein we have constructed chimeric viruses where regions of the murine leukemia virus (MuLV) Gag protein have been replaced with analogous sequences from human immunodeficiency virus type 1 (HIV-1). Here we describe the chimeric virus MuLV(MAHIV) which contains the HIV-1 matrix (MA) protein in place of the MuLV MA. MuLV(MAHIV) is infectious but grows at a reduced rate compared with wild-type MuLV. We found that the partial defect in replication of the chimeric virus is at a late stage in the viral life cycle. The MuLV(MAHIV) Gag proteins are distributed aberrantly within cells and are not associated with cellular membranes. Unlike MuLV, HIV-1 is able to integrate into growth-arrested cells. Incorporation of the HIV-1 MA, which is known to play a role in infection of nondividing cells, does not enable MuLV(MAHIV) to be expressed in growth-arrested cells. While it possesses no amino acid homology, we found that the HIV-1 MA can efficiently replace the MuLV matrix protein in infection.
Deminie
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CA
Program in Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Emerman
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D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002678:Chimera; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015488:HIV Antigens / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000502:physiology*; D051379:Mice; D011498:Protein Precursors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins; D014771:Virion; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015488:HIV Antigens; D011498:Protein Precursors; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1