Chimeric human immunodeficiency virus type 1 containing murine leukemia virus matrix assembles in murine cells

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Murine cells exhibit inefficient assembly and release of human immunodeficiency virus type 1 (HIV-1) virions.
• HIV-1 Gag polyprotein precursor targeting to the cell membrane is crucial for efficient virion assembly and release.
• This targeting process is mediated by the amino-terminal region of the Gag polyprotein.

Purpose of the Study:

• To overcome the assembly and release defect of HIV-1 in murine cells.
• To establish a functional murine model for HIV-1 replication studies.
• To investigate the role of matrix protein in HIV-1 assembly and infectivity.

Main Methods:

• Substitution of murine leukemia virus (MLV) matrix coding sequences into an infectious HIV-1 clone.
• Transfection of murine fibroblasts expressing human cyclin T1 with chimeric proviruses.
• Truncation of the gp41 cytoplasmic tail in chimeric viruses to prevent interference.

Main Results:

• Chimeric viruses demonstrated efficient assembly and release in murine cells expressing human cyclin T1.
• Truncated chimeric viruses could infect both human and murine cells.
• Replication was observed in human MT-4 cells with delayed kinetics, but not further in murine cells.

Conclusions:

• The substitution of MLV matrix sequences successfully compensated for the HIV-1 assembly block in murine cells.
• Truncated chimeric viruses exhibit a broader host range, infecting both human and murine cells.
• These findings provide a foundation for developing a murine model for HIV-1 replication, aiding in therapeutic research.