Inhibition of human immunodeficiency virus type 1 morphogenesis in T cells by alpha interferon.
Some murine retroviruses exhibit altered release of virus when cells are treated with alpha interferon (IFN-alpha), resulting in the accumulation of intracellular virions in cytoplasmic vacuoles. In studies of the inhibitory effect of IFN-alpha (Wellferon) on acute human immunodeficiency virus type 1 infection of human T-cell lines, we found that in C3 cells, the 50% effective concentration was 9 U/ml and the 90% effective concentration was 310 U/ml. There was no apparent accumulation of intracellular particles detected by p24 antigen levels or by processing the cells for electron microscopy. Extracellular reverse transcriptase activity and p24 levels decreased in parallel with increasing IFN, whereas the intracellular viral proteins decreased only slightly. By electron microscopy, cells treated with higher concentrations of IFN (512 U/ml) disclosed very few particles budding into extracellular spaces; no intracellular particles could be seen, despite nearly normal levels of intracellular viral protein detected by the p24 antigen assay and correct processing detected by Western blot (immunoblot) analysis. Thus in human immunodeficiency virus-infected cells, the major block produced by IFN-alpha appeared to be late in the viral cycle at the morphogenesis stage of virion production. Chronically infected Jurkat cells treated with IFN appeared to be inhibited in growth rate, as virus production decreased proportionally with cell number.
Smith
M S
MS
Lineberger Cancer Research Center, University of North Carolina, Chapel Hill 27599-7295.
Thresher
R J
RJ
Pagano
J S
JS
D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology; D000956:Antigens, Viral / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007424:Intracellular Fluid / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013601:T-Lymphocytes / Q000382:microbiology* / Q000502:physiology; D013997:Time Factors; D014758:Viral Core Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D007370:Interferon Type I; D012367:RNA, Viral; D014758:Viral Core Proteins; D014764:Viral Proteins; D012194:RNA-Directed DNA Polymerase