Characterization of Cells of the Myeloid-Monocytic Lineage (ML-1, HL-60, THP-1, U-937) Chronically Infected with the Human Immunodeficiency Virus-1

Abstract

The myeloid-monocytic cells ML-1, HL-60, THP-1 and U-937 were chronically infected (for more than 2 years) with the lymphotropic HIV-1 strain HTLV-IIIB. Reinfection experiments revealed that viruses obtained from chronically infected ML-1 /HIV-1 and HL-60/HIV-1 cells show a low infectivity if tested with uninfected ML-1 and HL-60 cells in contrast to virus preparations from chronically infected THP-l/HIV-1 and U-937/HIV-1 with their corresponding uninfected cell lines. Analyses of selected cell surface markers showed a differential expression of CD4, CD8, CD1 lc, CD 14, CD 15, CD20, HLA-DR and HLA-DQ in non- or chronically infected cells. During chronical infection, the myeloid-monocytic cells lost their reactivity with peroxidase and esterase. In chronically infected cells, the steady-state levels for TNF-α mRNA remained unchanged while those for IL-6 decreased. The half-lives of transcripts of both TNF-α (t½: 70 min) and IL-6 (t½: 100 min) were nearly the same in uninfected and chronically infected HL-60 cells.

Expression of CD4 Controls the Susceptibility of THP-1 Cells to Infection by R5 and X4 HIV Type 1 Isolates

“…20,22,31 Long-term, noncytopathic, productive infection of THP-1 cells with HIV-1 IIIB has produced chronically infected THP-1/IIIB cells. 22,24 The low syncytium formation ability of THP-1 cells incubated with MOLT4/HTLV-IIIB cells has been reported by Ushijima et al 20 Lack of syncytium formation after PMA treatment may be related to the low level of CD4. Similar results have been reported for PMA-treated U937 cells.…”

“…[17][18][19][20][21][22][23][24][25][26][27] After stimulation with phorbol 12-myristate 13-acetate (PMA), THP-1 cells are induced to differentiate into adherent macrophage-like cells, mimicking the monocyte-tomacrophage transformation. 28 THP-1 cells, growing as a single-cell suspension, are susceptible to infection by X4 HIV-1 isolates 18,20,[22][23][24][29][30][31] become susceptible to R5 isolates after treatment with differentiating agents. 23,32 Undifferentiated THP-1 cells undergo fusion mediated by recombinant envelope proteins from the X4, HIV-1 LAV strain but not from the R5, HIV-1 BaL isolate.…”

“…27 Discrepancies similar to those observed for the susceptibility of THP-1 cells to infection with X4 and R5 HIV-1 isolates have been reported also for the expression of the CCR5 coreceptor. Whereas several studies agreed that undifferentiated THP-1 cells express CD4 [18][19][20][22][23][24]29 and CXCR4, 33,34 conflicting results have been reported for CCR5. [32][33][34][35][36][37] It was reported before the identification of the HIV-1 coreceptors that PMA treatment of THP-1 cells, which renders them permissive to the R5 HIV-1 BaL , results in a decrease in surface CD4 levels below the threshold of detection by flow cytometry.…”

Myelomonocytic Cell Lines in Modeling HIV-1 Infection of the Bone Marrow

“…These cells have also been used to screen methodologies or drugs that may inhibit HIV-1 infection or reduce transcriptional activation of the virus [117,[160][161][162][163][164][165][166][167][168][169][170][171][172][173]. These cell lines have also been used in studies of drug toxicity, permeability, and/or effects on cellular activation and differentiation to gain an understanding of what specific drugs might do to cells in the bone marrow [144,154,[174][175][176][177][178][179][180][181][182][183], as well as determining what signaling pathways may play a role or become dysregulated [184][185][186][187][188][189]. Additionally, other studies have been completed that utilize these cells to examine the role that distinct viral determinants as well as specific host factors have on cellular tropism, cellular differentiation, and cytopathology [190][191][192][193].…”

Novel AgoshRNA molecules for silencing of the CCR5 co-receptor for HIV-1 infection

“…First and most importantly, the difficulty of keeping monocytes undifferentiated during this lengthy experiment. Alternatively, monocyte-derived cell lines such as THP-1 could be used, which maintain monocyte characteristics and do not express Dicer, but these cells cannot be infected by R5-tropic strains [56–58]. Differentiation into mature macrophage-like CCR5-positive cells could be induced by phorbol 12-myristate 13-acetate (PMA) [59], but these cells will also start expressing Dicer, which is incompatible with our experimental strategy.…”