Open AccessCharacterization of Human Immunodeficiency Virus Type 1 Replication in Immature and Mature Dendritic Cells Reveals Dissociablecis- andtrans-Infection
Author(s) -
Chunsheng Dong,
Alicia M. Janas,
Jianhua Wang,
Wendy J. Olson,
Li Wu
Publication year - 2007
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01081-07
Subject(s) - biology , virology , viral replication , cd40 , samhd1 , dendritic cell , virus , tumor necrosis factor alpha , immunology , reverse transcriptase , gene , immune system , in vitro , cytotoxic t cell , polymerase chain reaction , genetics
Dendritic cells (DCs) transmit human immunodeficiency virus type 1 (HIV-1) to CD4+ T cells through thetrans - andcis -infection pathways; however, little is known about the relative efficiencies of these pathways and whether they are interdependent. Here we comparecis - andtrans -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-α), 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-1cis -infection was partially restricted in TNF-α-induced mDCs and profoundly blocked in LPS-induced mDCs, these cells efficiently promoted HIV-1trans -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 dissociablecis - andtrans -infections.