Defective Human Immuno‐deficiency Virus (Hiv) Particles Produced by Cloned Cells of Htlv‐i‐carrying Mt‐4 Cells Persistently Infected With Hiv

Abstract

Persistently HIV‐infected cell lines were isolated from surviving and proliferating cells after infection of HTLV‐I‐carrying MT‐4 cells with cell‐free human immunodeficiency virus (HIV); HTLV‐IIIB and LAV. The media of the cloned cell cultures did not cause HIV infection of MT‐4, MOLT‐4, TALL‐1, or HL‐60 cells. Most of the constituents of the virus in the media were env proteins and many defective doughnut‐shaped particles released from the cells were identified by electron microscopy.

Cells surviving infection by human immunodeficiency virus type 1: vif or vpu mutants produce non-infectious or markedly less cytopathic viruses

“…About 85% of cell clones isolated from these persistently HIV-l-infected MT-4 or M 10 cells (MT-4/HIV-1 or M10/HIV-I, respectively) did not produce infectious HIV-1 particles (Yunoki et al, 1991). Thin-section electron microscopy revealed many abnormal morphologies among the HIV-1 particles released from these cell clones (Ikuta et al, 1988;Morita et al, 1990). In addition, structural analysis of HIV-I DNA by Southern hybridization revealed various kinds of proviral deletions in the cell clones .…”

“…We have reported an abnormal HIV-1 life cycle in persistently HIV-1-infected cells obtained after infection of human T cell lymphotrophic virus type I (HTLV-I)-transformed MT-4 cells or its clonal derivative M 10 with HIV-1 (Ikuta et al, 1988;Yunoki et al, 1991). The infected MT-4 and M10 cells were drastically reduced in number by single-cell killing rather than by the induction of syncytia.…”

Persistent infection of MT-4 cells by human immunodeficiency virus type 1 becomes increasingly likely with in vitro serial passage of wild-type but not nef mutant virus

“…In this system, infected cells were drastically reduced in number by the killing of single cells rather than by the induction of syncytia, a mechanism similar to that observed in normal peripheral blood mononuclear cells. However, a few surviving cells continued to grow at a significant rate and were found to have become persistently infected with HIV-1 (Ikuta et al, 1988). Considerable genetic and phenotypic diversity in the HIV-1 strains isolated after 15 serial passages of a clonal virus population in MT-4 cell cultures was recently reported (Sanchez-Palomino et al, 1993).…”

“…We have previously reported an abnormal HIV-1 life cycle in persistently HIV-l-infected cells obtained from the human T cell lymphotropic virus type I-transformed MT-4 cell line or from its clonal derivative, M10, after infection with HIV-1 (Ikuta et al, 1988;Yunoki et al, 1991). In this system, infected cells were drastically reduced in number by the killing of single cells rather than by the induction of syncytia, a mechanism similar to that observed in normal peripheral blood mononuclear cells.…”

Amino Acid 36 in the Human Immunodeficiency Virus Type 1 gp41 Ectodomain Controls Fusogenic Activity: Implications for the Molecular Mechanism of Viral Escape from a Fusion Inhibitor

“…We have previously reported that an established cell line, L-2, derived from MT-4 cells surviving after in vitro acutephase infection with an MT-4/MOLT-4 cell-propagated LAI strain, produces highly fusogenic but replication-defective HIV-1 particles (20). The L-2-produced viruses are peculiar, as the morphology of the viral particles is doughnut shaped since the protease gene is mutated and in that the virions harbor a robust activity to induce syncytia despite lacking infectivity (16,32).…”