Characterization of human immunodeficiency virus type 1 replication in immature and mature dendritic cells reveals dissociable cis- and trans-infection

Dong C, Janas AM, Wang JH, Olson WJ, Wu L
Source: J Virol
Publication Date: (2007)
Issue: 81(20): 11352-62
Research Area:
Immunotherapy / Hematology
Cells used in publication:
Dendritic cell (NHDC), human
Species: human
Tissue Origin: blood
Nucleofector® I/II/2b
DCs (0.8-1 x10^6) were transfected with 2 µg pmaxGFP or pNLAD8 (3 µg) using program U-002 and human DC Kit.
Dendritic cells (DCs) transmit human immunodeficiency virus type 1 (HIV-1) to CD4(+) T cells through the trans- and cis-infection pathways; however, little is known about the relative efficiencies of these pathways and whether they are interdependent. Here we compare cis- and trans-infections of HIV-1 mediated by immature DCs (iDCs) and mature DCs (mDCs), using replication-competent and single-cycle HIV-1. Monocyte-derived iDCs were differentiated into various types of mDCs by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), and CD40 ligand (CD40L). iDCs and CD40L-induced mDCs were susceptible to HIV-1 infection and mediated efficient viral transmission to CD4(+) T cells. Although HIV-1 cis-infection was partially restricted in TNF-alpha-induced mDCs and profoundly blocked in LPS-induced mDCs, these cells efficiently promoted HIV-1 trans-infection of CD4(+) T cells. The postentry restriction of HIV-1 infection in LPS-induced mDCs was identified at the levels of reverse transcription and postintegration, using real-time PCR quantification of viral DNA and integration. Furthermore, nucleofection of DCs with HIV-1 proviral DNA confirmed that impaired gene expression of LPS-induced mDCs was responsible for the postentry restriction of HIV-1 infection. Our results suggest that various DC subsets in vivo may differentially contribute to HIV-1 dissemination via dissociable cis- and trans-infections.