Perturbation of host-cell membrane is a primary mechanism of HIV cytopathology.
Cytopathic viruses injure cells by a number of different mechanisms. The mechanism by which HIV-1 injures T cells was studied by temporally examining host-cell macromolecular syntheses, stages of the cell cycle, and membrane permeability following acute infection. T cells cytopathically infected at an m.o.i. of 1-5 grew normally for 24-72 hr, depending on the cell line, followed by the first manifestation of cell injury, slowing of cell division. At that time significant amounts of unintegrated HIV DNA and p24 core protein became detectable, and acridine orange flow cytometric cell cycle studies demonstrated the presence of fewer cells in the G2/M stage of the cell cycle. There was no change in the frequency of cells in the S-stage, and metabolic pulsing with radioactive precursors demonstrated that host-cell DNA, RNA, and protein syntheses were normal at that time and normal up to the time cells started to die (approximately 24 hr later), when all three decreased. Cellular lipid synthesis, however, was perturbed when cell multiplication slowed, with phospholipid synthesis reduced and neutral lipid synthesis enhanced. Permeability of the host-cell membrane to small molecules, such as Ca2+ and sucrose, was slightly enhanced early postinfection, and by the time of slowing of cell division, host membrane permeability was greatly increased to both Ca2+ and sucrose (Stokes radius 5.2 A) but not to inulin (Stokes radium 20 A). These changes in host-cell membrane permeability and phospholipid synthesis were not observed in acutely infected H9 cells, which are not susceptible to HIV cytopathology. Thus, HIV-1 appeared to predominantly injure T cells by perturbing host-cell membrane permeability and lipid synthesis, which is similar to the cytopathic mechanisms of paramyxoviruses.
Cloyd
M W
MW
Department of Microbiology, University of Texas Medical Branch, Galveston, Texas 77550.
Lynn
W S
WS
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics; D002453:Cell Cycle; D002460:Cell Line; D002462:Cell Membrane / Q000382:microbiology; D002463:Cell Membrane Permeability; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000096:biosynthesis; D015683:Gene Products, gag / Q000235:genetics; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D010743:Phospholipids / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000382:microbiology*; D014758:Viral Core Proteins / Q000235:genetics
D004279:DNA, Viral; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D010743:Phospholipids; D012367:RNA, Viral; D014758:Viral Core Proteins