Loss of infectivity by progeny virus from alpha interferon-treated human immunodeficiency virus type 1-infected T cells is associated with defective assembly of envelope gp120.
Levels of human immunodeficiency virus (HIV) DNA, RNA, or p24 antigen and reverse transcriptase activity in T-cell cultures treated with 500 IU of recombinant alpha interferon (rIFN alpha) per ml were comparable to those in control cultures. Radioimmunoprecipitation analysis of proteins in lysates of IFN-treated T cells documented a marked accumulation of HIV proteins. Localization of gp120 by immunofluorescence showed a diffuse pattern in IFN-treated cells quite distinct from the ring pattern in untreated control cells. That large quantities of gp120 in aberrant cell compartments might affect HIV morphogenesis was confirmed in infectivity studies: virions from IFN-treated cells were 100- to 1,000-fold less infectious than an equal number of virions from control cells. Direct examination of IFN-treated and control HIV-infected cells by transmission electron microscopy showed little difference in the number or distribution of viral particles. However, quantitation of gp120 by immunogold particle analysis revealed a marked depletion of envelope glycoprotein in virions released from IFN-treated cells. This defect in gp120 assembly onto mature viral particles provides a molecular basis for this loss of infectivity.
D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000032:analysis / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D012367:RNA, Viral / Q000032:analysis / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D014764:Viral Proteins / Q000302:isolation & purification / Q000378:metabolism*; D014771:Virion / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*
D004279:DNA, Viral; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D007370:Interferon Type I; D012367:RNA, Viral; D011994:Recombinant Proteins; D014764:Viral Proteins; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase