Inhibition of human immunodeficiency virus type 1 morphogenesis in T cells by alpha interferon

Abstract

Some murine retroviruses exhibit altered release of virus when cells are treated with alpha interferon (IFN-oa), resulting in the accumulation of intraceUlular virions in cytoplasmic vacuoles. In studies of the inhibitory effect of IFN-ac (Welferon) 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 intracelular particles detected by p24 antigen levels or by processing the cells for electron microscopy. ExtraceUlular 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/mi) 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-a 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.

Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15

“…In vitro, type I IFN inhibits HIV-1 infection both at early steps of replication (24,25) and at the late steps of virus assembly and release (26)(27)(28). HIV-1 virions assembled in IFN-treated T cells show a low infectivity, accumulate at the plasma membrane, and have altered morphogenesis (29)(30)(31). Similar defects were seen in IFN-treated cells infected with murine leukemia virus (32).…”

In VitroEvaluation and Characterization of Newly Designed Alkylamidophospholipid Analogues as Anti-Human Immunodeficiency Virus Type 1 Agents

“…Published evidence indicates that the major antiviral effect of recombinant interferon α (rIFN-α) operates in the stages of virus assembly of gp120 and release (Hansen et al, 1992;Smith et al, 1991;Willey et al, 1988). Syntheses of HIV-1-induced DNA, RNA and protein were minimally inhibited by rIFN-α but virus particles released from the treated cells were 100-to 1000-fold less infectious, owing to an assembly defect in gp120 (Hansen et al, 1992).…”

Partial Inhibition of Human Immunodeficiency Virus Replication by Type I Interferons: Impact of Cell-to-Cell Viral Transfer

“…IFN treatment of primary T lymphocytes, macrophages, and some T-cell lines efficiently inhibits early phases of infection, including HIVinduced cell fusion and reverse transcription (15,16,26,27,46,60,61,70). IFN also impair later steps of the HIV replication cycle, ranging from reduced virus protein processing and stability to altered virion release and composition (2,8,17,19,20,23,26,28,39,49,63,71,72). In these early reports, the experimental systems were optimized to measure the effect of IFN on either early or late steps of the virus replication cycle but did not fully explore the long-term efficacy of IFN.…”