Mutual interactions between HIV-1 and cytokines in adherent cells during acute infection

Abstract

The production of cytokines by HIV-infected cells from adherent tissues as well as their effects on HIV replication in the same cells were investigated. CD4-transfected HeLa-T4-6c epithelial cells, CD4-positive normal lung fibroblasts and CD4-negative RD rhabdomyosarcoma cells were infected with HIV-1. All cultures were permissive for virus replication, which was completed within 48-72 h by Hela-T4-6c and RD cells and 2-3 weeks in normal fibroblasts. During the course of HIV replication, a series of cytokines (particularly IL-6 and TNF alpha) was produced and released in parallel to the peak of virus growth, in amounts varying with the cell system studied. Treatment of cultures with recombinant cytokines given at concentrations in the range of those induced by HIV-1 indicated that IL-6 and TNF alpha caused an increase of: i) CD4 expression, ii) HIV absorption to uninfected cells, and iii) release of infectious virions by infected cells. The fact that HIV-1 absorption and spread can be mediated by HIV-induced cytokines may be relevant in the pathogenesis of the in vivo disease, as it may constitute a possible self-enhancing model of HIV infection also in the solid tissues.

Infectious Virus with Reduced Cytopathogenicity Resulting from Persistent Infection of Normal Lung Fibroblasts by HIV Type 1 Strains

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] As shown by an experiment on PEU cells in Fig. 1A and B), both strains replicated and were released.…”

“…Our studies of HIV-infected human diploid fibroblasts indicate that virus replication is also stimulated by tumor necrosis factor a in these targets,5 and that HIV-inductive cytokines are produced in vitro by fibroblasts and other cells from solid tissues, in parallel to HIV replication.20 Thus inflammatory stimuli causing the local release of cytokines would enhance HIV production by stromal cells, hence accelerating virus transmission both within the organ and to infiltrating cells. 20 …”

Short Communication: Characterization of an HIV Type 1 Strain with Preferential Replication in Adherent Cells

“…Various human cell types were exposed to HIV-T and HIV-E (MOI of 2 pg/cell) for 1 hr at 0°C, to determine the extent of HIV binding, as described. 17,22 As shown in Fig. 1A, the amounts of HIV-T bound to C8166 cells, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDMs) were higher compared with HIV-E, which, conversely, showed higher binding to PEU diploid fibroblasts 20 of different origin, such as colonic HT-29, mammary MEC-1, 8 renal MC mesangial, and proximal tubular epithelial cells, 23 and uroepithelial T-24 cells.…”

“…B OTH ex vivo AND in vitro STUDIES showed that human immunodeficiency virus type 1 (HIV-1) infects epithelial cells from different body sites, such as the oral cavity, 1 gastrointestinal tract, 2-5 mammary glands, 6-8 adrenal glands, 9 salivary glands, 10 kidney, [11][12][13] liver, 14 thymus, 15 and eye. 16 Cells of the genital tract are infected in vitro, 2,10,17 but no ex vivo evidence of HIV replication has been found so far. 18,19 In epithelial cells and fibroblasts the replication rate is low, although significant, 8,12,20,21 and persistent infections can occur.…”

“…Tropism characterization, stock preparations, and evaluation of adsorption, entry, and replication were published. 17,22 HeLa-T4 cells were originally infected with purified, T-derived virus at a multiplicity of infection (MOI) of 0.5 syncytium-forming units (SFU)/cell. Cells were initially cocultured with uninfected epithelial cells, with one-third of the cells being replaced twice a week with fresh cells for 5 weeks; uninfected cells were not required after that, because persistent infection had been established.…”